NMSC

Download as pdf or txt
Download as pdf or txt
You are on page 1of 52

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

Basal Cell Skin Cancer


Version 1.2023 — March 10, 2023

NCCN.org

NCCN Guidelines for Patients® available at www.nccn.org/patients

Continue

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

*Chrysalyne D. Schmults, MD, MS/Chair ϖ ≠ ¶ Jeffrey M. Farma, MD ¶ Igor Puzanov, MD, MSCI † ‡
Dana-Farber/Brigham and Women’s Fox Chase Cancer Center Roswell Park Comprehensive Cancer Center
Cancer Center Karthik Ghosh, MD Þ Jeffrey Scott, MD, MHS ϖ ¶
Rachel Blitzblau, MD, PhD/Vice Chair § Mayo Clinic Comprehensive Cancer Center The Sidney Kimmel Comprehensive
Duke Cancer Institute Roy C. Grekin, MD ϖ ¶ Cancer Center at John Hopkins
Sumaira Z. Aasi, MD ϖ UCSF Helen Diller Family Aleksandar Sekulic, MD, PhD ϖ
Stanford Cancer Institute Comprehensive Cancer Center Mayo Clinic Comprehensive Cancer Center
Murad Alam, MD, MBA, MSCI ϖ ¶ ζ Kelly Harms, MD, PhD ϖ Ashok R. Shaha, MD ¶
Robert H. Lurie Comprehensive Cancer University of Michigan Rogel Cancer Center Memorial Sloan Kettering Cancer Center
Center of Northwestern University Alan L. Ho, MD, PhD † Divya Srivastava, MD ϖ
Arya Amini, MD § Memorial Sloan Kettering Cancer Center UT Southwestern Simmons
City of Hope National Medical Center John Nicholas Lukens, MD § Comprehensive Cancer Center
Brian C. Baumann, MD § Abramson Cancer Center Valencia Thomas, MD ϖ
Siteman Cancer Center at Barnes- at the University of Pennsylvania The University of Texas
Jewish Hospital and Washington Lawrence Mark, MD, PhD ϖ MD Anderson Cancer Center
University School of Medicine Indiana University Melvin and Bren Simon Yaohui G. Xu, MD, PhD ϖ Ÿ
Jeremy Bordeaux, MD, MPH ϖ Comprehensive Cancer Center University of Wisconsin
Case Comprehensive Cancer Center/ Theresa Medina, MD † Carbone Cancer Center
University Hospitals Seidman Cancer University of Colorado Cancer Center Mehran Yusuf, MD §
Center and Cleveland Clinic Taussig O’Neal Comprehensive Cancer Center at UAB
Cancer Institute Kishwer S. Nehal, MD ϖ ¶
Memorial Sloan Kettering Cancer Center
Pei-Ling Chen, MD, PhD ≠
Moffitt Cancer Center Paul Nghiem, MD, PhD ϖ NCCN
Fred Hutchinson Cancer Center Sara Espinosa, PhD
Robert Chin, MD, PhD §
UCLA Jonsson Comprehensive Cancer Center Kelly Olino, MD ¶ Rashmi Kumar, PhD
Yale Cancer Center/Smilow Cancer Hospital Beth McCullough, RN, BS
Carlo M. Contreras, MD ¶
The Ohio State University Comprehensive Soo Park, MD †
Cancer Center - James Cancer Hospital UC San Diego Moores Cancer Center
and Solove Research Institute ϖ Dermatology
Tejesh Patel, MD ϖ ≠ ‡ Hematology/Hematology oncology
Dominick DiMaio, MD ≠ St. Jude Children’s Research Hospital/The Þ Internal medicine
Fred & Pamela Buffett Cancer Center University of Tennessee Health Science Center † Medical oncology
ζ Otolaryngology
Jessica M. Donigan, MD ϖ ¶
≠ Pathology/Dermatopathology
Huntsman Cancer Institute § Radiotherapy/Radiation oncology
at the University of Utah Ÿ Reconstructive surgery

NCCN Guidelines Panel Disclosures


Continue ¶ Surgery/Surgical oncology
* Discussion Section Writing Committee
Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

NCCN Basal Cell Skin Cancer Panel Members


Summary of the Guidelines Updates Clinical Trials: NCCN believes that
the best management for any patient
Clinical Presentation, Workup, and Risk Status (BCC-1) with cancer is in a clinical trial.
Treatment for Low-Risk BCC (BCC-2) Participation in clinical trials is
Treatment for High-Risk BCC (BCC-3) especially encouraged.
Follow-up and Recurrence or Advanced Disease (BCC-4)
Find an NCCN Member Institution:
Principles of Pathology (BCC-A) https://www.nccn.org/home/member-
Stratification to Determine Treatment Options for Local BCC Based on Risk Factors for Recurrence (BCC-B) institutions.
Principles of Treatment (BCC-C)
NCCN Categories of Evidence and
Principles of Radiation Therapy (BCC-D)
Principles of Systemic Therapy (BCC-E) Consensus: All recommendations
Principles of Cancer Risk Assessment and Counseling (BCC-F) are category 2A unless otherwise
indicated.
Abbreviations (ABBR-1) See NCCN Categories of Evidence
and Consensus.

The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to
treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual
clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations
or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN
Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not
be reproduced in any form without the express written permission of NCCN. ©2023.
Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

Updates in Version 1.2023 of the NCCN Guidelines for Basal Cell Skin Cancer from Version 2.2022 include:
BCC-1
• Preliminary Workup:
Bullet removed: Complete skin exam.
Bullet added: Shave excision if applicable.
• New option header added: Additional Workup
New option added: Complete skin examination.
• Risk Status, middle pathway following High risk, new option added: Consider imaging if clinical exam insufficient for following disease.
• Footnote d revised: Extensive disease includes deep structural involvement such as bone, named nerves perineural disease, and deep soft tissue. If
perineural disease of named nerve(s) is suspected, MRI with contrast is preferred. If bone disease is suspected, CT with contrast is preferred unless
contraindicated.
BCC-2
• Primary Treatment:
Top option revised: Curettage and electrodisiccation (C&E) or shave excision: Excluding terminal hair-bearing areas, such as the scalp, pubic and
axillary regions, and beard area in males. or.
Second option revised: If tumor appears to extend beyond the dermis, surgical or shave excision should generally be performed rather than C&E.
New option added: Topical therapy.
• Footnote removed: For tumors on cheeks, forehead, scalp, neck, and pretibia that are <6 mm in depth and confined to the dermis, C&E may
be considered as an alternative primary treatment option if Mohs, resection with PDEMA, and standard excision are not feasible due to patient
comorbidities. See Risk Factors for Recurrence (BCC-B).
• New footnotes added:
Footnote l: Mohs surgery should be performed by dermatologic surgeons who have specialized training and experience in this procedure. (Also page
BCC-3A)
Footnote m: As per other appropriate use criteria. Task Force/Committee Members, Vidal CL, Armbrect EA, Andrea AA, et al. J Am Acad Dermatol
2019;80:189-207.e11. (Also page BCC-3A)
BCC-3
• Primary Treatment, new option added: For patients in whom surgery may cause significant functional damage, neoadjuvant administration of
vismodegib followed by PDEMA may be considered (category 2B).

Continued

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
UPDATES
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

Updates in Version 1.2023 of the NCCN Guidelines for Basal Cell Skin Cancer from Version 2.2022 include:
BCC-3A
• Footnotes revised:
Footnote n: For complicated cases (eg, locally advanced disease, where high chance of surgical cure is in question (extensive disease where surgery
and/or RT are unlikely to result in a cure or are not feasible), consider multidisciplinary consultation. For locally advanced disease in which curative
RT and curative surgery are not feasible, consider and treatment with hedgehog pathway inhibitors (HHIs) (vismodegib and sonidegib) or programmed
cell death protein 1 (PD-1) inhibitor (cemiplimab-rwlc) for patients previously treated with an HHI or for whom an HHI is not appropriate. Feasibility of
surgery or radiation should be assessed by a surgeon and radiation oncologist. Principles of Systemic Therapy (BCC-E).
Footnote o: For tumors on cheeks, forehead, scalp, neck, and pretibia that are clinically diagnosed non-facial BCCs <6 mm in depth on the head, neck,
hands, feet, pretibia, and anogenital that are clinically and confined to the dermis, C&E or shave excision may be considered as an alternative primary
treatment option if Mohs, resection with PDEMA, and standard excision are not feasible difficult to perform due to patient comorbidities (eg thrombocytopenia,
immunosuppression, bleeding diathesis, multiple primary BCCs). Risk Factors for Recurrence (BCC-B).
Footnote r: If large named nerve involvement is suspected, consider MRI with contrast of region of interest to evaluate extent and rule out base of
skull involvement or intracranial extension in head and neck tumors.
• New footnote t added: In one study of 55 patients with locally advanced basal cell carcinoma, neoadjuvant administration of vismodegib before
planned surgery allowed for a smaller surgical procedure in 71% of patients, although carried a high (36.4%) recurrence risk. Bertrand N, et al.
EClinicalMedicine 2021;35:100844.
BCC-4
• Recurrence or Advanced Disease:
Following Primary or recurrent nodal metastases, second bullet revised: Programed cell death protein 1 (PD-1) inhibitor C(cemiplimab-rwlc).
Following Distant metastases, second bullet revised: PD-1 inhibitor C(cemiplimab-rwlc).
• New footnote u added: Follow-up with a dermatologist is strongly recommended if any of the following criteria are met: past or imminent solid organ,
marrow, or stem cell transplant, one or more cutaneous melanomas in the past 5 years, or four or more non-melanoma skin cancers in the past 5 years.
BCC-A
• Principles of Biopsy Reporting:
New bullet added: The intent of a biopsy is for diagnosis, not to assess the margin status.
Bullets revised:
◊ Second bullet: Pathologic evaluation of skin biopsies is ideally performed by a dermatologist, pathologist, or dermatopathologist, or Mohs surgeon
who is experienced in interpreting cutaneous neoplasms.
◊ Third bullet: Clinical information to be submitted on biopsy requisition includes patient demographics age and gender, clinical diameter of lesion,
anatomic location, and prior treatment of lesion. Additional helpful features to include are immunosuppression and history of RT.
◊ Fourth bullet: Pathologic report should include histologic subtype and presence of any features that would increase the risk for local recurrence,
including invasion of tumor beyond reticular dermis and presence and extent of perineural invasion (if involving nerve below the dermis or >0.1 mm
in caliber).

Continued

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
UPDATES
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

Updates in Version 1.2023 of the NCCN Guidelines for Basal Cell Skin Cancer from Version 2.2022 include:
BCC-A (continued)
• Principles of Excision Reporting:
New bullet added: The intent of excision is to clear the tumor and thus margin status needs to be reported.
Bullets revised:
◊ Third bullet: Clinical information to be submitted on excision requisition includes patient demographics age and gender, anatomic location, clinical
diameter of lesion, and additional clinical information listed above under Principles of Biopsy Reporting.
◊ Fourth bullet: Minimal reporting elements to be reported for all surgical specimens include histologic subtype of basal cell carcinoma (BCC),
invasion of tumor beyond deep reticular dermis, presence of perineural invasion (if involving nerve below dermis or if largest nerve involved is >
≥0.1 mm in caliber) and angiolymphatic invasion, and peripheral and deep margin status.
• Reference 1 revised: Alam M, Armstrong A, Baum C, et al. Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad
Dermatol 2018;78:560-578 Work Group; Invited Reviewers, Kim JYS, et al. Guidelines of care for the management of basal cell carcinoma. J Am Acad
Dermatol 2018;78:540-559.
BCC-B
• Stratification to Determine Treatment Options for Local BCC Based on Risk Factors for Recurrence, Location/size, High Risk, description removed:
Cheeks, forehead, scalp, neck, and pretibia (any size).
• Footnote d revised: Having basosquamous, (mixed) infiltrative, sclerosing/morpheaform, micronodular, morpheaform, basosquamous, sclerosing, or
and BCC with carcinosarcomatous differentiation features in any portion of the tumor. In some cases basosquamous tumors may be prognostically
similar to squamous cell carcinoma (SCC); clinicopathologic correlation is recommended in these cases to further consider prognostic implication is
recommended in these cases.
BCC-C
• Second bullet revised: Surgical approaches often offer the most effective and efficient means for accomplishing cure, but considerations of function
and patient preference may lead to choosing RT/topical therapy/systemic therapy as primary treatment in order to achieve optimal satisfactory overall
results.
• Third bullet revised: In certain patients at high risk for multiple primary tumors (eg, basal cell nevus syndrome [Gorlin syndrome], xeroderma
pigmentosum, history of RT), increased surveillance and consideration of prophylactic measures may be indicated. Consider referring patients with
suspected basal cell nevus syndrome (Gorlin syndrome) or xeroderma pigmentosum for genetic evaluation.
• New footnote a added: Mohs surgery should be performed by dermatologic surgeons who have specialized training and experience in this procedure.

Continued

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
UPDATES
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

Updates in Version 1.2023 of the NCCN Guidelines for Basal Cell Skin Cancer from Version 2.2022 include:
BCC-D
• General Principles, second bullet revised: RT is contraindicated for genetic conditions predisposing to skin cancer (eg, basal cell nevus syndrome
[Gorlin syndrome]) and relatively contraindicated for patients with connective tissue diseases (eg, scleroderma).
• General Treatment Information, new bullet added: Radiation treatments should be given by a practicing radiation oncologist with radiation physics
support to meet established quality assurance and dosimetric constraints.
• Significant changes made to the Recommended RT Dosing Prescription Regimen Table.
New bullets added below table:
◊ BED = Biologic Effective Dose
◊ Conventionally fractionated radiotherapy consists of five daily treatments per week.
◊ Hypofractionated radiotherapy consists of daily treatments or 2 to 4 treatments per week. Fraction sizes larger than 6 Gy are not routinely
recommended outside of the palliative setting.
• New footnote a added: ASTRO Guidelines on Definitive and Postoperative Radiation Therapy for Basal and Squamous Cell Cancers of the Skin.
BCC-E
• First bullet, sub-bullet revised: Locally advanced disease is defined by those that have primary or recurrent local extensive disease that are not
amenable to where surgery and/or RT are unlikely to result in a cure.
• Third bullet revised: Multidisciplinary consultation may be required to determine the best treatment approach and deem the tumor not amenable to
surgery or radiation RT.
• Fourth bullet, first sub-bullet revised: Hedgehog pathway inhibitors (HHIs) (ie, vismodegib, sonidegib).
First sub-bullet revised: Due to frequency of intolerable side effects associated with HHIs, drug holidays or other alternatives to daily dosing can be
used to reduce side effects to improve adherence to therapy and quality of life (see Discussion for details).
Second sub-bullet revised: HHIs may be considered for diffuse BCC formation (eg, basal cell nevus syndrome [Gorlin syndrome] or other genetic
forms of multiple BCC). HHIs are not FDA approved for basal cell nevus syndrome (Gorlin syndrome); however, they may be used off-label and are
effective based on a randomized controlled trial.
• New bullet added: The role of adjuvant systemic therapy for resected BCC is unclear and thus, adjuvant systemic therapy is best performed in a clinical
trial setting.
BCC-F
• New page added: Principles of Cancer Risk Assessment and Counseling
ABBR-1
• New page added: Abbreviations.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
UPDATES
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

CLINICAL PRELIMINARY DIAGNOSIS ADDITIONAL RISK STATUS


PRESENTATION WORKUP WORKUP

Primary Treatment
Low risk of Low-Risk BCC
(BCC-2)

Lesion • H&P Consider imaging


suspicious • Biopsyb,c Basal cell Complete Primary Treatment
if clinical exam
for skin • Shave excision if carcinoma skin High riskc,d,f insufficient for of High-Risk BCC
cancera applicable (BCC) examination (BCC-3)
following diseaseg

Initial
Imaging studies of
presentation Treatment for
areas of interest
of regional Recurrence or
as indicated for
or distant Advanced Disease
suspicion of
metastatic (BCC-4)
extensive diseased,g
diseasee

a For more information, see American Academy of Dermatology Association.


b Principles of Pathology (BCC-A).
c Risk Factors for Recurrence (BCC-B).
d Extensive disease includes deep involvement such as bone, named nerves, and deep soft tissue. If disease of named nerve(s) is suspected, MRI with contrast is
preferred. If bone disease is suspected, CT with contrast is preferred unless contraindicated.
e For rare cases that present with regional or distant metastatic disease at diagnosis, treat as nodal or distant metastases pathway on BCC-4.
f Any high-risk factor places the patient in the high-risk category.
g Imaging modality and targeted area should be at the discretion of the treating team based on the suspected extent of disease (ie, local, regional, metastatic). Histologic
confirmation is often sufficient to diagnose local recurrence, but MRI can be considered to assess extent of local disease. For nodal or distant metastasis, histologic
analysis and/or CT imaging can be used for confirmation and to gauge extent of disease.

Note: All recommendations are category 2A unless otherwise indicated.


Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
BCC-1
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

PRIMARY TREATMENTh ADDITIONAL TREATMENT


Curettage and electrodesiccation (C&E) or shave excision

or

If tumor appears to extend beyond the dermis, surgical or shave


excision should generally be performed rather than C&E

or Mohsl,m or other forms of peripheral


and deep en face margin assessment
Standard excision with 4-mm clinical (PDEMA)k
margins and postoperative margin Positive
margins or
assessment. Tissue rearrangement Re-excision if clinically feasible Follow-up
Low-risk (eg, flap reconstruction, extensive or (BCC-4)
BCCb,c undermining) should not be RTj for non-surgical candidatesh
undertaken until clear margins are
identified (second intention healing, Negative
linear repair, or skin graft are margins
acceptable)

or

Topical therapyi
or
Radiation therapy (RT)j for non-surgical candidatesh

b Principles of Pathology (BCC-A).


c Risk Factors for Recurrence (BCC-B). j Principles of Radiation Therapy (BCC-D).
h Principles of Treatment (BCC-C). k PDEMA with permanent section analysis or intraoperative frozen section analysis is an
i In patients with superficial basal cell skin
cancer, therapies such as topical alternative to Mohs. See Principles of PDEMA Technique (SCC-G).
imiquimod, topical 5-fluorouracil, photodynamic therapy, or cryotherapy l Mohs surgery should be performed by dermatologic surgeons who have specialized
may be considered, although cure rates are approximately 10% lower than training and experience in this procedure.
for surgical treatment modalities. Jansen MHE, et al. J Invest Dermatol m As per other appropriate use criteria. Task Force/Committee Members, Vidal CI, Armbrect
2018;138:527-533. Drew BA, et al. Dermatol Surg 2017;43:1423-1430. EA, Andrea AA, et al. J Am Acad Dermatol 2019;80:189-207.e11.

Note: All recommendations are category 2A unless otherwise indicated.


Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
BCC-2
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

PRIMARY TREATMENTh ADDITIONAL TREATMENT


Multidisciplinary consultation to discuss
options:
Positive
• Re-resect, if feasible
margins
• RTj
• Systemic therapyq if curative surgery
Mohsl,m or other and/or curative RT not feasibleh,n
forms of PDEMAk,o

or
Negative If extensive perineural or large-nerve
margins involvement,b,r consider adjuvant RT h,j,s
Standard excision
with wider surgical
marginsp and
postoperative
margin assessment Mohsl,m or other If residual disease is present, and
High-risk and second intention forms of PDEMA,k,o if further surgery is not feasible, Follow-up
BCCb,c,f,n healing, linear repair, feasible consider multidisciplinary (BCC-4)
Positive
or skin graft or consultation to discuss options:
margins
Standard re-excision • RTj
if PDEMAk,o is not • Systemic therapyq if curative RT
or feasible is not feasiblen

For non-surgical candidatesh,n:


• RTj
• Systemic therapyq if curative RT is not feasiblen

or

For patients in whom surgery may cause


significant functional damage, neoadjuvant
administration of vismodegib followed by PDEMA
may be considered (category 2B)q,t

Footnotes on BCC-3A

Note: All recommendations are category 2A unless otherwise indicated.


Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
BCC-3
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

FOOTNOTES
b Principles of Pathology (BCC-A).
c Risk Factors for Recurrence (BCC-B).
f Any high-risk factor places the patient in the high-risk category.
h Principles of Treatment (BCC-C).
j Principles of Radiation Therapy (BCC-D).
k PDEMA with permanent section analysis or intraoperative frozen section analysis is an alternative to Mohs. See Principles of PDEMA Technique (SCC-G).
l Mohs surgery should be performed by dermatologic surgeons who have specialized training and experience in this procedure.
m As per other appropriate use criteria. Task Force/Committee Members, Vidal CI, Armbrect EA, Andrea AA, et al. J Am Acad Dermatol 2019;80:189-207.e11.
n For locally advanced disease (extensive disease where surgery and/or RT are unlikely to result in a cure or are not feasible), consider multidisciplinary consultation
and treatment with hedgehog pathway inhibitors (HHIs) (vismodegib and sonidegib) or programmed cell death protein 1 (PD-1) inhibitor (cemiplimab-rwlc) for patients
previously treated with an HHI or for whom an HHI is not appropriate. Feasibility of surgery or radiation should be assessed by a surgeon and radiation oncologist.
Principles of Systemic Therapy (BCC-E).
o For clinically diagnosed non-facial BCCs <6 mm in depth on the head, neck, hands, feet, pretibia, and anogenital that are clinically confined to the dermis, C&E or
shave excision may be considered as an alternative primary treatment option if Mohs, resection with PDEMA, and standard excision are difficult to perform due to
patient comorbidities (eg, thrombocytopenia, immunosuppression, bleeding diathesis, multiple primary BCCs). Risk Factors for Recurrence (BCC-B).
p Due to the wide variability of clinical characteristics that may define a high-risk tumor, it is not feasible to recommend a defined margin for standard excision of high-risk
BCC. Keen awareness of the subclinical extension of BCC is advised when selecting a treatment modality without complete margin assessment for a high-risk tumor.
These margins may need to be modified based on tumor- or patient-specific factors.
q Principles of Systemic Therapy (BCC-E).
r If named nerve involvement is suspected, consider MRI with contrast of region of interest to evaluate extent and rule out base of skull involvement or intracranial
extension in head and neck tumors.
s There are conflicting data about the value of adjuvant RT following margin-negative surgical excision, particularly after Mohs.
t In one study of 55 patients with locally advanced basal cell carcinoma, neoadjuvant administration of vismodegib before planned surgery allowed for a smaller surgical
procedure in 71% of patients, although it carried a high (36.4%) recurrence risk. Bertrand N, et al. EClinicalMedicine 2021;35:100844.

Note: All recommendations are category 2A unless otherwise indicated.


Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
BCC-3A
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

FOLLOW-UP RECURRENCE OR ADVANCED DISEASE


Follow Primary Treatment pathway for high-
Local recurrence
risk disease (BCC-3)

Multidisciplinary consultation
to consider one or more of the following options:
Surgery
or
If surgery is not feasible then RTj or systemic
Primary or recurrent therapyq
nodal metastases • Hedgehog pathway inhibitor (HHI)
• H&P Vismodegib
Including complete skin Sonidegib (category 2B)
exam every 6–12 mo for • Programmed cell death protein 1 (PD-1)
the first 5 years, and then inhibitor (cemiplimab-rwlc)w
at least annually for lifeu • Clinical trial
• Consider imaging if clinical
exam is insufficient for
following the diseasev Multidisciplinary consultation to consider:
• Patient education: Systemic therapyq
Sun protection • HHI
Self-examination Vismodegib
Distant metastases • PD-1 inhibitor (cemiplimab-rwlc)w
or
RTj or surgery for limited metastatic diseasex
or
Palliation and best supportive care

j Principles of Radiation Therapy (BCC-D).


q Principles of Systemic Therapy (BCC-E).
u Follow-up with a dermatologist is strongly recommended if any of the following criteria are
met: past or imminent solid organ, marrow, or stem cell transplant, one or more cutaneous
melanomas in the past 5 years, or four or more non-melanoma skin cancers in the past 5 years. w Cemiplimab-rwlc is recommended for patients with locally advanced
v Imaging modality and targeted area should be at the discretion of the treating team based or metastatic basal cell carcinoma (mBCC) previously treated with an
on the suspected extent of disease (ie, local, regional, metastatic). Histologic confirmation is HHI or for whom an HHI is not appropriate.
often sufficient to diagnose local recurrence, but MRI can be considered to assess extent of x Under highly selective circumstances, in the context of
local disease. For nodal or distant metastasis, histologic analysis and/or CT imaging can be multidisciplinary consultation, resection of limited metastases can be
used for confirmation and to gauge extent of disease. considered.

Note: All recommendations are category 2A unless otherwise indicated.


Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
BCC-4
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

PRINCIPLES OF PATHOLOGY
Principles of Biopsy Reporting:
• The intent of a biopsy is for diagnosis, not to assess the margin status.
• Pathologic evaluation of skin biopsies is ideally performed by a dermatologist, pathologist, dermatopathologist, or Mohs surgeon who is
experienced in interpreting cutaneous neoplasms.
• Clinical information to be submitted on biopsy requisition includes patient age and gender, clinical diameter of lesion, anatomic location,
and prior treatment of lesion. Additional helpful features to include are immunosuppression and history of RT.
• Pathologic report should include histologic subtypea and presence and extent of any features that would increase the risk for local
recurrence, including invasion of tumor beyond reticular dermis and presence of perineural invasion.1

Principles of Excision Reporting:


• The intent of excision is to clear the tumor and thus margin status needs to be reported.
• Saucerization specimens intended for definitive surgical therapy should be labeled as such, as they can be histopathologically difficult to
distinguish from shave biopsies but must be evaluated for margin status.
• Clinical information to be submitted on excision requisition includes patient age and gender, anatomic location, clinical diameter of lesion,
and additional clinical information listed above under Principles of Biopsy Reporting.
• Minimal reporting elements to be reported for all surgical specimens include histologic subtype of BCC,a invasion of tumor beyond deep
reticular dermis, presence of perineural invasion (if involving nerve below dermis or if largest nerve involved is ≥0.1 mm in caliber) and
angiolymphatic invasion, and peripheral and deep margin status.
• For Mohs excisions, reporting of these elements is also encouraged. Since depth of invasion (in mm) may not be ascertained on
tangentially cut Mohs specimens, anatomic level of invasion should be reported. Frozen or permanent section analysis of the clinical
tumor specimen may be undertaken if needed for complete reporting of features associated with poor prognosis.2

a Low-risk histologic subtypes include nodular, superficial, and other non-aggressive growth patterns such as keratotic, infundibulocystic, and fibroepithelioma of Pinkus;
high-risk subtypes include basosquamous, infiltrative, sclerosing/morpheaform, micronodular, and BCC with carcinosarcomatous differentiation.
1 Work Group; Invited Reviewers, Kim JYS, et al. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol 2018;78:540-559.
2 Morgan FC, Ruiz ES, Karia PS, et al. Brigham and Women's Hospital tumor classification system for basal cell carcinoma identifies patients with risk of metastasis and
death. J Am Acad Dermatol 2021;85:582-587.

Note: All recommendations are category 2A unless otherwise indicated.


Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
BCC-A
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

STRATIFICATION TO DETERMINE TREATMENT OPTIONS FOR LOCAL BCC BASED ON RISK FACTORS
FOR RECURRENCEa

Risk Group Low Risk High Risk

Treatment options BCC-2 BCC-3

H&P
Trunk, extremities ≥2 cm
Location/size Trunk, extremities <2 cm Head, neck, hands, feet, pretibia, and anogenital (any size)c
Borders Well-defined Poorly defined
Primary vs. recurrent Primary Recurrent
Immunosuppression (-) (+)
Site of prior RT (-) (+)
Pathology (BCC-A)
Subtype Nodular, superficialb Aggresive growth patternd
Perineural involvement (-) (+)

a Any high-risk factor places the patient in the high-risk category.


b Low-risk histologic subtypes include nodular, superficial, and other non-aggressive growth patterns such as keratotic, infundibulocystic, and fibroepithelioma of Pinkus.
c This area constitutes high risk based on location, independent of size. Narrow excision margins due to anatomic and functional constraints are associated with
increased recurrence rates with standard histologic processing. Complete margin assessment such as with Mohs or PDEMA is recommended for optimal tumor
clearance and maximal tissue conservation. For tumors <6 mm in size, without other high-risk features, other treatment modalities may be considered if at least 4-mm
clinically tumor-free margins can be obtained without significant anatomic or functional distortions.
d Having basosquamous, infiltrative, sclerosing/morpheaform, micronodular, and BCC with carcinosarcomatous differentiation features in any portion of the tumor. In
some cases, basosquamous tumors may be prognostically similar to squamous cell carcinoma (SCC); clinicopathologic correlation is recommended in these cases to
further consider prognostic implication.

Note: All recommendations are category 2A unless otherwise indicated.


Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

BCC-B
Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

PRINCIPLES OF TREATMENT

• The primary treatment goal of basal cell skin cancer is the complete removal of the tumor and the maximal preservation of function and
cosmesis. All treatment decisions should be customized to account for the particular factors present in the individual case and for the
patient’s preference.

• Surgical approaches often offer the most effective and efficient means for accomplishing cure, but considerations of function and patient
preference may lead to choosing RT/topical therapy/systemic therapy as primary treatment in order to achieve satisfactory overall results.

• In certain patients at high risk for multiple primary tumors (eg, basal cell nevus syndrome [Gorlin syndrome], xeroderma pigmentosum,
history of RT), increased surveillance and consideration of prophylactic measures may be indicated. Consider referring patients with
suspected basal cell nevus syndrome (Gorlin syndrome) or xeroderma pigmentosum for genetic evaluation.

• In patients with superficial basal cell skin cancer, therapies such as topical imiquimod, topical 5-fluorouracil, photodynamic therapy (eg,
aminolevulinic acid [ALA], porfimer sodium), or cryotherapy may be considered, even though the cure rates may be lower than with surgical
treatment modalities.

• When Mohsa with margin assessment is being performed and the preoperative biopsy is considered insufficient for providing all the staging
information required to properly treat the tumor, submission of the central specimen for vertical paraffin-embedded permanent sections or
documentation of staging parameters in Mohs report is recommended.

• Use of nicotinamide may be effective in reducing the development of basal cell skin cancers.1,2

a Mohs surgery should be performed by dermatologic surgeons who have specialized training and experience in this procedure.
1 Chen AC, Martin AJ, Dalziell RA, et al. A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients. Br J
Dermatol 2016;175:1073-1075.
2 Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med 2015;373:1618-1626.

Note: All recommendations are category 2A unless otherwise indicated.


Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
BCC-C
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

PRINCIPLES OF RADIATION THERAPY


General Principlesa
• Protracted fractionation is associated with improved cosmetic results and should be utilized for poorly vascularized or cartilaginous areas.
• RT is contraindicated for genetic conditions predisposing to skin cancer (eg, basal cell nevus syndrome [Gorlin syndrome]) and relatively contraindicated
for patients with connective tissue diseases (eg, scleroderma).
• Given higher complication rates, re-irradiation should not be routinely utilized for recurrent disease within a prior radiation field.
• Isotope-based brachytherapy can be an effective treatment for certain sites of disease, particularly on the head and neck.
• There are insufficient long-term efficacy and safety data to support the routine use of electronic surface brachytherapy.

General Treatment Information


• Radiation treatments should be given by a practicing radiation oncologist with radiation physics support to meet established quality assurance and
dosimetric constraints.

Primary Tumor RT Dosing


Definitive RT BED10 of 70–93 Gy for conventional fractionation
BED10 of 56–88 Gy for hypofractionation
Postoperative adjuvant RT BED10 of 60–79 Gy for conventional fractionation
BED10 of 56–70 Gy for hypofractionation
Regional Disease
• Lymph node regions, after lymph node dissection
Negative margins, no Extracapsular Extension (ECE) 50–60 Gy over 5 to 6 weeks
Positive margins or ECE 60–66 Gy over 6 to 7 weeks
• Lymph node regions, without lymph node dissection
Clinically negative, at risk 50 Gy over 5 to 7 weeks
Clinically positive 60–70 Gy over 6 to 7 weeks
• Clinically at-risk nerves 50–60 Gy over 5 to 6 weeks

• BED = Biologic Effective Dose


• Conventionally fractionated radiotherapy consists of five daily treatments per week.
• Hypofractionated radiotherapy consists of daily treatments or 2 to 4 treatments per week. Fraction sizes larger than 6 Gy are not routinely recommended
outside of the palliative setting.

a ASTRO Guideline on Definitive and Postoperative Radiation Therapy for Basal and Squamous Cell Cancers of the Skin.

Note: All recommendations are category 2A unless otherwise indicated.


Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
BCC-D
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

PRINCIPLES OF SYSTEMIC THERAPY


Locally Advanced (laBCC) or Metastatic Basal Cell Carcinoma (mBCC)
Approach
• Systemic therapy may be considered for laBCC and mBCC. It is not used where topical therapy, surgery, or RT is likely to be curative.
Locally advanced disease is defined by those that have primary or recurrent extensive disease where surgery and/or RT are unlikely to
result in a cure.
• Systemic therapy may be considered for cases of nodal or distant metastatic disease, especially if surgery and RT are not feasible.
• Multidisciplinary consultation may be required to determine the best treatment approach and deem the tumor not amenable to surgery or RT.
• Systemic therapy options include:
Hedgehog pathway inhibitors (HHIs) (ie, vismodegib, sonidegib1).
◊ Due to frequency of intolerable side effects associated with HHIs, drug holidays or other alternatives to daily dosing can be used to
reduce side effects to improve adherence to therapy and quality of life.
◊ HHIs may be considered for diffuse BCC formation (eg, basal cell nevus syndrome [Gorlin syndrome] or other genetic forms of multiple
BCC). HHIs are not FDA approved for basal cell nevus syndrome (Gorlin syndrome); however, they may be used off-label and are
effective based on a randomized controlled trial.2
◊ Current FDA-approved HHIs include vismodegib and sonidegib.1 Vismodegib is FDA approved for the treatment of adults with mBCC
or laBCC that has recurred following surgery, or those who are not candidates for surgery or RT. Sonidegib1 is FDA approved for the
treatment of adults with laBCC that has recurred following surgery or RT, or those who are not candidates for surgery or RT. Sonidegib is
not FDA approved for the treatment of adults with mBCC.
Cemiplimab-rwlc is recommended for patients with laBCC or mBCC previously treated with an HHI or for whom an HHI is not appropriate.
• The role of adjuvant systemic therapy for resected BCC is unclear and thus, adjuvant systemic therapy is best performed in a clinical trial
setting.

1 Dummer R, Guminksi A, Gutzmer R, et al. Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase II
randomized, double-blind BOLT study. Br J Dermatol 2020;182:1369-1378.
2 Tang JY, Ally MS, Chanana AM, et al. Inhibition of the hedgehog pathway in patients with basal-cell nevus syndrome: final results from the multicentre, randomised,
double-blind, placebo-controlled, phase 2 trial. Lancet Oncol 2016;17:1720-1731.

Note: All recommendations are category 2A unless otherwise indicated.


Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
BCC-E
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

PRINCIPLES OF CANCER RISK ASSESSMENT AND COUNSELING


• The decision to offer genetic testing involves three related stages:
1) Pre-test counseling prior to ordering testing;
2) Consideration of the most appropriate testing strategy; and
3) Testing result disclosure and post-test counseling.
• In certain patients at high risk for multiple primary tumors (eg, basal cell nevus syndrome [Gorlin syndrome], xeroderma pigmentosum,
history of RT), increased surveillance and consideration of prophylactic measures may be indicated. Patients with these conditions should
be referred to a cancer center with particular expertise in BCC prevention and prophylaxis.
• It is recommended that a genetic counselor, medical geneticist, endocrinologist, oncologist, surgeon, oncology nurse, or other health
professional with expertise and experience in cancer genetics be involved at each stage whenever possible. Clinicians without direct referral
access to the appropriate expertise should be aware of the telehealth genetic counseling options available. These resources can be found
through the National Society of Genetic Counselors (NSGC) “Find a Genetic Counselor” tool (www.nsgc.org).

See the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic for the following:
• Principles of Cancer Risk Assessment and Counseling (EVAL-A)
• Pedigree: First-, Second-, and Third-Degree Relatives of Proband (EVAL-B)
• General Testing Criteria (CRIT-1)

Note: All recommendations are category 2A unless otherwise indicated.


Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
BCC-F
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

ABBREVIATIONS

BCC basal cell carcinoma


BED biologically effective dose

C&E curettage and


electrodessication

ECE extracapsular extension

H&P history and physical


HHI hedgehog pathway inhibitors

mBCC metastatic basal cell


carcinoma

NSGC National Society of Genetic


Counselors

PDEMA peripheral and deep en face


margin assessment

RT radiation therapy

ABBR-1
Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023 NCCN Guidelines Index


Table of Contents
Basal Cell Skin Cancer Discussion

NCCN Categories of Evidence and Consensus


Category 1 Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3 Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise indicated.

Version 1.2023, 03/10/2023 © 2023 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
CAT-1
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Discussion This discussion corresponds to the NCCN Guidelines for Basal Cell Skin Cancer. Last updated: January 31st, 2022.

Table of Contents

Overview ..................................................................................... MS-2


Literature Search Criteria and Guidelines Update Methodology .... MS-2
Genetics ...................................................................................... MS-2
Clinical Presentation and Workup ................................................ MS-3
Risk Stratification of Local BCC Based on Risk Factors for Recurrence
................................................................................................... MS-3
History & Physical Examination ................................................ MS-3
Pathology ................................................................................. MS-4
Treatment Modalities for BCC ...................................................... MS-5
Curettage and Electrodesiccation ............................................. MS-5
Standard Excision with Postoperative Margin Assessment........ MS-6
Mohs Micrographic Surgery and Peripheral and Deep En Face
Margin Assessment .................................................................. MS-6
Radiation Therapy .................................................................... MS-7
Superficial Therapies................................................................ MS-8
Systemic Therapy .................................................................. MS-10
Follow-up .................................................................................. MS-12
References ................................................................................ MS-13

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-1
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Overview PubMed database was chosen as it remains the most widely used
Basal cell carcinoma (BCC) is the most common cancer in the United resource for medical literature and indexes peer-reviewed biomedical
States. It is estimated that BCCs occur in 2 million Americans annually, literature.28
exceeding the incidence of all other cancers combined.1-3 BCCs are at
The search results were narrowed by selecting studies in humans
least 2 times more common than squamous cell carcinomas (SCCs),
published in English. Results were confined to the following article
the second most common type of skin cancer.1-6 Furthermore, the
types: Clinical Trial; Guideline; Meta-Analysis; Randomized Controlled
incidence of this common malignancy is rising rapidly.1,3,6,7 Compared
Trial; Systematic Reviews; and Validation Studies.
with SCC, BCCs are much less likely to metastasize, with a metastatic
rate of <0.1%, and thus generally have a good prognosis.8-10 Although The data from key PubMed articles as well as articles from additional
rarely metastatic, BCC can produce substantial local destruction along sources deemed as relevant to these guidelines and discussed by the
with disfigurement and may involve extensive areas of soft tissue, panel have been included in this version of the Discussion section (eg,
cartilage, and bone. e-publications ahead of print, meeting abstracts). Recommendations for
which high-level evidence is lacking are based on the panel’s review of
A number of risk factors are associated with development of BCC. The
lower-level evidence and expert opinion.
most recognized environmental carcinogen is sunlight. Evidence
reveals that the relationship between sun exposure and BCC is The complete details of the Development and Update of the NCCN
complex, depending on the timing, pattern and amount of ultraviolet Guidelines are available at www.NCCN.org.
(UV) radiation.11-15 Fair skin, red or blond hair, and light eye color are
associated with BCC as independent risk factors due to greater Genetics
susceptibility to UV damage.13,15-22 BCC risk is increased by both UV-A Extensive research has led to advances in the understanding of the
and -B radiation as well as by ionizing radiation. Radiation treatment genetics of BCC. The sonic hedgehog signaling pathway has emerged
(RT) for other conditions, especially at a young age, is also associated as playing a pivotal role in the pathogenesis of BCC, and mutations in a
with an increased risk for developing BCC.23-27 Most BCC tumors number of molecules in this pathway have been implicated in the
develop on skin sites exposed to radiation—either from the sun or from development of the disease.29-31 Mutations in the PTCH1 (patched 1)
therapy.23-25 gene on chromosome 9q, which codes for the sonic hedgehog receptor,
are the underlying cause of nevoid BCC syndrome, and are present in
Literature Search Criteria and Guidelines Update
approximately 30% to 90% of sporadic BCCs.32-40 Specific UV-induced
Methodology
mutations in the tumor suppressor gene p53 appear to be a common
Prior to the update of this version of the NCCN Clinical Practice event in BCC development.34,37,40,41 Certain genetic syndromes greatly
Guidelines in Oncology (NCCN Guidelines®) Basal Cell Skin Cancer, an predispose affected individuals to skin cancer formation, including BCC,
electronic search of the PubMed database was performed to obtain key such as albinism42,43 and xeroderma pigmentosum (in which defects
literature using the following search term: basal cell carcinoma. The exist in UV light-induced unscheduled DNA repair).44-50

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-2
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Clinical Presentation and Workup sufficient to diagnose local recurrence, but MRI can be considered to
On clinical presentation of the patient with lesion suspicious of skin assess extent of local disease. For nodal or distant metastases,
cancer, workup for BCC begins with a history and physical examination, histologic analysis and/or CT imaging can be used for confirmation and
with an emphasis on a complete skin examination. A full skin to gauge extent of disease.
examination is recommended, because individuals with skin cancer
History & Physical Examination
often have additional, concurrent precancers or cancers located at
other, usually sun-exposed skin sites. These individuals are also at Location and Size
increased risk of developing cutaneous melanoma.51 A skin biopsy is Anatomic location56-62 and size58-64 have been known to be a risk factor
then performed on any suspicious lesion. The biopsy should include for BCC recurrence and metastasis for many years. In general, BCCs
deep reticular dermis. This procedure is preferred because an infiltrative that develop in the head and neck area, which includes the “H zone” or
histology may sometimes be present only at the deeper, advancing “mask area” of the face, are more likely to recur than those that develop
margins of a tumor, and superficial biopsies will frequently miss this on the trunk and extremities. Based on a 27-year retrospective review of
component.52,53 5755 BCCs, recurrences were significantly more common when tumors
in high-risk locations (central face, eyebrows, nose, lips, chin, ear,
Risk Stratification of Local BCC Based on Risk Factors temple, genitalia, nipples/areola, hands, feet, ankles nail units) were
for Recurrence greater than or equal to 6 mm in diameter and when tumors in
After workup, a risk assessment should be performed to determine the moderate-risk locations (cheeks, forehead, scalp, neck, jawline, pretibial
treatment plan. The NCCN Panel examined risk factors for BCC surface) were greater than or equal to 10 mm in diameter.65 More
associated with recurrence (Refer to Guidelines section BCC-B Risk recently, the American Academy of Dermatology in collaboration with
Factors for Recurrence). Any high-risk factor places the patient in the American College of Mohs Surgery, American Society for Dermatologic
high-risk category. Skin lesions in high-risk populations may be difficult Surgery Association, and American Society for Mohs Surgery
to assess clinically; therefore, a low threshold for performing skin developed an appropriate use criteria document in the treatment of
biopsies in these patients is necessary. For rare cases that present with cutaneous neoplasms based on 270 clinical scenarios including 69
regional or distant metastatic disease at diagnosis, the disease should BCCs,66 which has been incorporated into Guidelines section BCC-B
be treated as nodal or distant metastases. Imaging studies may be Risk Factors for Recurrence.
clinically evident when extensive disease, such as bone involvement,
Clinical Borders and Primary Versus Recurrent Disease
perineural invasion (PNI), or deep soft tissue involvement, is suspected.
The low- and high-risk factors of well-defined versus ill-defined clinical
If perineural disease is suspected, MRI with contrast is preferred.54,55 If
tumor borders67-69 and primary versus recurrent disease,60,68,70
bone disease is suspected, CT with contrast is preferred unless
respectively, have been extensively documented in the literature.
contraindicated. Imaging modality and targeted area should be at the
discretion of the treating team based on the suspected extent of
disease (ie, local, regional, metastatic). Histologic confirmation is often

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-3
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Immunosuppression aggressive subtypes include the keratotic variant, infundibulocystic
Settings of immunosuppression, such as organ transplantation,71-76 and variant, and fibroepithelioma of Pinkus.
long-term use of psoralen and UVA light (PUVA),77,78 increase the
incidence of BCC. In particular, among patients who have had organ Basosquamous carcinomas are tumors of which have the histologic
transplants, BCC incidence is approximately 5- to 10-fold higher than in appearance of both a BCC and an SCC. Some basosquamous tumors
the general population,79-81 occurring in up to half of patients during the are the result of a BCC colliding with an adjacent SCC. Others
10 years following transplant.82-85 Several large retrospective studies represent truly biphenotypic tumors, many of which may have started as
found that BCCs in patients who had received organ transplants were BCC, but have subsequently undergone prominent partial squamous
more likely to have the superficial histologic subtype and to occur in metaplasia.98 Data suggest that basosquamous carcinomas have a
extracephalic locations and in younger patients (mean age of onset 15 metastatic capacity that is more similar to that of SCC than BCC.99-101
years lower). 86-88 Two of these studies showed similar low recurrence
Perineural Involvement
rates for transplant recipients and controls.87,88 Nevertheless, because
PNI is uncommon in any nonmelanoma skin cancer (NMSC) (2%–6%),
of NCCN Guidelines Panel Members’ own anecdotal experiences, the
and develops less frequently and is less aggressive in BCC versus
panel decided to classify BCCs developing in settings of
SCC.102-107 BCC with PNI poses a greatly increased risk of recurrence,
immunosuppression as potentially high-risk tumors.
and is associated with other risk factors including previous recurrent
Site of Prior Radiotherapy tumors, high grade, larger lesion size, and infiltrating, morpheaform, and
Tumors developing in sites of prior RT refer to primary BCCs arising in basosquamous subtypes.106,108,109 If large nerve involvement is
areas previously irradiated for unrelated conditions. All recurrent suspected, MRI should be considered to evaluate extent and/or rule out
tumors, irrespective of prior therapy, are defined as high risk. Data from skull involvement in those with head and neck tumors.55,110-112
a number of studies with large sample sizes support that prior RT for
Age and Its Effect on BCC Behavior
unrelated, frequently benign conditions is a risk factor for BCC
Whether young age (typically ≤40 years) is an independent risk factor
development.23-27,89,90
for aggressive BCC behavior is debatable. An analysis of a large
Pathology database of patients with BCC (N = 3381) documented an increased
percentage of BCC with aggressive histologic growth patterns in young
Pathologic Subtypes
persons.113 In contrast, results from other analyses of large databases
Histologic subtyping of BCC as a predictor of risk of recurrence is a
(N = 1000 to >10,000) indicate that patients presenting with BCC at a
well-established concept.91,92 The subtypes encompassed by the term
young age are more likely to have the superficial subtype.114-117 Other
“aggressive growth pattern,” including micronodular, infiltrative,
analyses report no significant differences in BCC histologic subtype
sclerosing, and morpheaform (or desmoplastic) patterns, are more likely
between young versus older patients.118-120 The relationship between
to recur than the nodular and superficial BCC.63,67,68,70,93-97 Non-
tumor location and patient age is also unclear, as several studies
showed that younger patients were more likely to present with BCCs on

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-4
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
the trunk or extremities,114,119,121,122 but other studies found no significant Treatment Modalities for BCC
association.118 Curettage and Electrodesiccation
Most large studies (N = 50-2000) have shown no significant association Although a fast and cost-effective technique for superficial lesions,
between age and recurrence rate.60,68,118,120 One multivariate analysis, curettage and electrodesiccation (C&E) does not allow histologic margin
however, showed a positive relationship between increasing age and assessment. Studies have reported overall 5-year recurrence rates
likelihood of recurrence.123 Age has also been evaluated as a risk factor ranging from 1.2% to 40% in patients with BCC selected for C&E, with
for developing a second or multiple BCCs.63,120,122-130 Many of these high-risk locations and histologically aggressive subtypes reporting
studies used fairly large databases (N = 200–2500), and found that risk higher recurrence rates.58,133-141
of developing more than one BCC is associated with increased
This technique is deemed effective for properly selected, local, low-risk
age.63,120,122-125,127,129,130 On the contrary, an analysis of a very large
BCC with three caveats.58,139 First, C&E should not be used to treat
database (N = 71,924) found a significantly higher risk of subsequent
areas with terminal hair growth such as the scalp, pubic and axillary
NMSC in patients younger than 40 years at the time of their first BCC
regions, or beard area in males due to the risk that a tumor extending
diagnosis.131 In addition, an analysis of 100 metastatic BCC cases
down follicular structures might not be adequately removed. Second, if
found that patients with distant metastases tended to be younger than
the subcutaneous layer is reached during the course of C&E, then
those with only regional metastases.132 Consistent with this idea, the
surgical excision should generally be performed instead. This change in
Rotterdam Study showed that while the risk of developing a second
therapy is necessary as the effectiveness of the C&E technique rests on
BCC increased with age,130 the risk of developing multiple BCC lesions
the ability of the clinician to distinguish between firm, normal dermis,
was highest in patients who were younger than 65 years at the time of
and soft tumor tissue when using a sharp curette. Since subcutaneous
their first BCC diagnosis.128 Taken together, these studies suggest that
adipose is even softer than tumor tissue, the ability of the curette to
young age, in and of itself, is not considered a risk factor for aggressive
distinguish and, therefore, selectively and completely remove tumor
BCC. Nevertheless, there is a small subset of patients who develop
cells diminishes. Third, if C&E has been performed based only on the
BCC at a young age and may have particularly aggressive disease.
appearance of a low-risk tumor, biopsy results of the tissue taken at the
These patients may benefit from regular follow-up.
time of C&E should be reviewed to make sure that there are no
high-risk pathologic features that would require additional therapy. For
tumors on the cheeks, forehead, scalp, neck, and pretibial that are less
than 6 mm in depth and confined to the dermis, C&E may be
considered as an alternative primary treatment option if Mohs
micrographic surgery (Mohs) or resection with peripheral and deep en
face margin assessment (PDEMA), and standard excision are not
feasible due to patient comorbidities.

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-5
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Standard Excision with Postoperative Margin Assessment specific factors. When standard excision with wider surgical margins
Another therapeutic option for BCC is standard surgical excision yields positive margins, Mohs) or other forms of PDEMA or standard re-
followed by postoperative pathologic evaluation of margins. This excision is recommended (if PDEMA is not feasible).
technique has been reported to achieve 5-year recurrence rates of 0.8%
For either local, low-risk or local, high-risk BCC, when standard excision
to 17.4% for BCC, with lower recurrence rates associated with low-risk
is used, tissue rearrangement (eg, flap reconstruction, extensive
tumors and higher recurrence rates associated with high-risk
undermining) should not be undertaken until clear margins are
tumors.133,135,141-144 Studies have reported variable margins required to
identified. Second intention healing, linear repair, or skin graft are
completely excise 95% of all tumor.145-149 These margins have been
acceptable options.
suggested to be 2 to 4 mm for low-risk, well-demarcated tumors smaller
than 2 cm,145-149 whereas margins of 4 to 6 mm,146 and in one study, 8 Mohs Micrographic Surgery and Peripheral and Deep En
mm145 were suggested for high-risk BCC. Given this wide variability, Face Margin Assessment
studies have reported incomplete excision rates after standard excision Mohs is the preferred surgical technique over standard excision for re-
ranging from 3.2% to 61.5% depending on tumor location, histologic excision of local, low-risk BCC after positive margins with standard
subtype, and medical provider’s specialty.150-159 Therefore, excision, as well as the primary surgical technique of choice for local,
postoperative margin assessment and identification of clear margins are high-risk BCC because it allows intraoperative analysis of 100% of the
critical to ensure favorable outcomes with standard excision. excision margin. Mohs is also recommended when standard excision
with wider surgical margins is unable to achieve negative margins in
The clinical margins chosen by the panel for the primary treatment of
local, high-risk BCC. Two meta-analyses published in 1989 associated
local, low-risk BCC are based on the work of Zitelli et al.160 Their
Mohs with 5-year recurrence rates of 1.0% for primary BCC, and 5.6%
analysis indicated that for well-circumscribed BCC lesions smaller than
for recurrent BCC.133,141 In these studies, the recurrence rates for Mohs
2 cm in diameter, excision with 4-mm clinical margins should result in
were lower than those for standard excision (10.1% and 17.4% for
complete removal in more than 95% of cases. The indications for this
primary and recurrent BCC, respectively), and lower than those for any
approach were also expanded to include re-excision of low-risk primary
other treatment modality included in the analysis (C&E, cryotherapy,
BCC if positive margins are obtained after an initial excision with
and RT).133,141 More recent studies on the long-term outcomes (~ 4
postoperative margin assessment. For local, high-risk BCC, standard
years) of Mohs have reported overall recurrence rates of 2.9% to
excision with wider surgical margins is recommended as the primary
3.8%,161,162 specifically 0% to 6.5% for primary and 4% to 20% for
treatment. Due to the wide variability of clinical characteristics that may
recurrent BCCs.92,163-168 The only prospective randomized trial
define a high-risk tumor, it is not feasible to recommend a defined
comparing Mohs to standard excision reported fewer 10-year
margin for standard excision of high-risk BCC. Kean awareness of the
recurrences with Mohs for both primary (2.5% vs. 4.1%; P = .397) and
subclinical extension of BCC is advised when selecting a treatment
recurrent BCC (2.4% vs. 12.1%; P = .015), although the difference was
modality without complete margin assessment for a high-risk tumor.
only statistically significant for recurrent tumors. Importantly, a large
These margins may need to be modified based on tumor- or patient-
proportion of recurrences occurred more than 5 years after

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-6
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
treatment.169-171 Besides lower recurrence rates, Mohs has also been about the value of adjuvant RT following margin-negative surgical
associated with significant tissue sparing compared with standard excision, particularly after Mohs. For local, high-risk BCC that has
excision.172,173 It has been demonstrated that H-zone location, recurrent undergone multiple resections, and further surgery is not feasible, RT is
tumor, aggressive subtype, PNI, and tumor size greater than or equal to recommended as part of multidisciplinary consultation if residual
11 mm are significantly associated with two or more Mohs stages.108,174 disease is present. For specifics about the application of RT, refer to
However, superficial BCC, despite being generally considered less Guidelines section BCC-D Principles of Radiation Therapy.
aggressive, was shown in a Brazilian study to be 9.03 times more likely
to require more than one Mohs stage, likely due to “skip areas” and Two meta-analyses reported 5-year recurrence rates of 8.7% and 9.8%
clinically indistinct borders.175 after RT on primary and recurrent BCC, respectively.133,141
Retrospective analyses of BCC treated with RT have reported 5-year
Excision with PDEMA with permanent section analysis or intraoperative local control, cure, or complete response rates ranging from 93% to
frozen section analysis is an acceptable alternative to Mohs provided it 96%,180-183 and 5-year recurrence rates from 4% to 16%.184-186 Efficacy
includes a complete assessment of all deep and peripheral margins. A of RT was better for BCCs that were less advanced, primary (vs.
5-year recurrence rate of 0.58% has been reported with slow Mohs recurrent), or had smaller diameter or nodular histologic
using formalin-fixed paraffin-embedded sections and delayed closure in subtype.180,181,183-185 A prospective study randomizing 347 patients to
a UK-based prospective study.176 The descriptive term PDEMA receive either surgery (standard excision with free margins ≥2 mm from
underscores the panel’s belief that complete histologic assessment of visible borders) or RT as primary treatment of BCC reported higher
the entire marginal surface is the key to optimal tumor removal. For recurrence rates with RT than surgery (7.5% vs. 0.7%; P = .003),187
more information, refer to the NCCN Guidelines® for Squamous Cell poorer cosmetic outcomes, and more postoperative complications.188
Skin Cancer SCC-G Principles of PDEMA Technique.
A small number of prospective studies have reported high rates of
Radiation Therapy tumor control with specific radiation dose fractionation regimens for
Although surgery is the mainstay of local treatment for BCC, small BCCs.187,189,190 A recent systematic review and meta-analysis also
consideration of function and patient preference and other factors may reported hypo-fractionated RT regimens associated with positive
lead to the choice of RT as primary therapy for both local, low-risk and cosmetic outcomes.191 The NCCN Panel recommends ranges of
local, high-risk BCC.177 The recommendations for RT extend to electron beam dose and fractionation that can be used for definite RT
additional treatment for local, low-risk BCC after positive margins with and postoperative adjuvant RT. Isotope-based brachytherapy can be an
standard excision. RT is also recommended for local, high-risk BCC as effective treatment for certain sites of disease, particularly on the head
additional treatment after positive margins with Mohs or other forms of and neck.192-195 However, there are insufficient long-term efficacy and
PDEMA and adjuvant treatment after negative margins with Mohs or safety data to support the routine use of electronic surface
other forms of PDEMA in case of extensive perineural or large-nerve brachytherapy.196,197
involvement.178 In these patients, local control has been reported to be
50% to 90% with postoperative RT.177,179 There are conflicting data
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-7
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Superficial Therapies terms of disease control.143,221-228 Data from clinical trials reported cure
In patients with superficial BCC, therapies such as topical imiquimod, rates from 60% to 100% by PDT for patients with BCC.224,229-234 Most of
topical 5-fluorouracil (5-FU), photodynamic therapy (PDT), or these studies have focused on the superficial and nodular histologic
cryotherapy may be considered, although cure rates are approximately subtypes, and several have found higher cure rates for superficial
10% lower than for surgical treatment modalities.198-200 These options versus nodular subtypes in both low- and high-risk locations.224,229,234
are also recommended for patients where surgery or RT is Ulceration and thickness are associated with lower response to
contraindicated or impractical. therapy,234 and within the nodular subtype, cure rates are better with
thinner lesions.223 Clinical studies have demonstrated PDT activity
Topical Therapies against “difficult-to-treat” lesions, with 24-month complete response rate
Imiquimod was found to be effective for treating nodular201,202 and of 78%.229,235 Currently, PDT is being used at some NCCN Member
superficial201,203-206 BCC in randomized studies. Two 5-year follow-up Institutions for premalignant or superficial low-risk lesions on any
studies reported overall treatment success rates of 80.4% and 77.9%, location on the body, although response rates may be higher on the
respectively, in patients with superficial BCC treated with face and scalp.236,237
imiquimod.205,207 Recurrence seems to be associated with tumor
thickness.208 A phase III randomized trial in patients with superficial or Cryotherapy
nodular BCC showed that imiquimod provided an 82.5% clinical Cryotherapy has been used for many years as a fast and cost-effective
success rate.209,210 For all of these studies, tumors in the H-zone were means for removal of BCCs. Systematic reviews of historical data in
excluded. Although the clinical success rate was significantly higher primary BCCs have reported recurrence rates for cryotherapy ranging
with surgical excision using a 4-mm margin (97.7%; P < .001), cosmetic from 0% to 13%, and mean recurrence rates from pooled analyses
outcomes by dermatologist assessment were significantly better with ranging between 3% and 4%.133,135,238,239 In prospective trials,
imiquimod (excellent/good at 3-year follow-up: 61% vs. 36%; P < .001). cryotherapy has been shown to result in recurrence rates ranging from
Another topical cream with efficacy against BCC is fluorouracil (5- 5% to 39%.189,240-242 A key limitation of cryotherapy is poorer cosmetic
FU),211,212 which has been shown in a large randomized trial to have a outcomes compared with other treatment options, as demonstrated by
5-year tumor-free survival probability of 70.0%.199,213,214 Other studies prospective randomized trials.241-243
have reported cure rates of up to 90% with this treatment.215-217
Comparisons of Superficial Therapies
Photodynamic Therapy Several randomized studies and meta-analyses have compared
PDT with photosensitizing agents including methyl aminolevulinate superficial therapies for BCC (Table 1). In summary, these studies
(MAL), 5-aminolevulinic acid (ALA), and porfimer sodium is another indicate that in patients with superficial BCC, PDT has similar efficacy
option for superficial BCC.218-220 MAL is no longer produced in the as cryotherapy but much better cosmetic outcomes. Whereas a meta-
United States. Multiple randomized trials and a meta-analysis have analysis of 23 randomized and non-randomized trials found no
shown that rates of excellent or good cosmetic outcomes were higher significant difference in efficacy for PDT versus imiquimod,244 a more
with PDT versus surgery, although surgery was superior to PDT in recent randomized trial showed that treatment success was more likely

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-8
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
with imiquimod.199,214 This study also demonstrate superior imiquimod during treatment administration, imiquimod and 5-FU are more likely to
outcomes compared to 5-FU cream. Exploratory sub-analyses found cause moderate to severe local swelling, erosion, crust formation,
that treatment success rates were significantly higher with imiquimod for itching, and wound infections.213 Both cryotherapy and PDT are
tumors that are large or truncal, while PDT provided significantly better associated with pain during and after treatment, and data from a
outcomes in elderly patients with lesions on the lower extremities.245 randomized trial indicate a trend toward a higher likelihood of pain with
Safety results showed that while PDT causes moderate to severe pain PDT.241

Table 1. Studies Comparing Superficial Therapies in Patients with Superficial BCC


Histologic Tumor Locations
Study Treatments (n) Efficacy Cosmetic Outcome
Subtype
Phase III randomized trial Superficial Trunk, limb, head, neck Cryosurgery (39) 1-year 15% } NS Excellent: 8% } P < .001
Wang 2001241 and nodular ALA-PDT (44) recurrence: 25% 50%

Randomized trial Superficial Trunk, limb, head, neck, Cryotherapy (58) 5-year 20% } NS Excellent: 16% } P = .00078
Basset-Seguin 2008242 face MAL-PDT (60) recurrence: 22% 60%
Meta-analysis Superficial Locations depend on Imiquimod (1088) 1-year 87% } NS
Roozeboom 2012244 individual studies PDT (934) tumor-free 84% NR
survival:
Randomized, single-blind, Superficial
non-inferiority trial
Jansen 2018199
Trunk, limb, head, neck MAL-PDT (202) Treatment
Imiquimod cream (198) Successa:
Fluorouracil cream (201)
63% } P < .001
81%
70 } P =.04
} NS
Good/ 62% All comparisons NS
excellent: 61%
58%
MAL, methyl aminolevulinate; NR, not reported; NS, no statistically significant difference; PDT, photodynamic therapy.
aTreatment success was defined as the product of the percent of patients with clearance at 3 months by the percentage with sustained clearance during the next 9 months.

Nicotinamide in Reducing BCC Development


Data from phase II and phase III randomized trials indicated that
treatment of actinic keratoses with nicotinamide reduced the occurrence
of new BCCs, specifically by 20% at 12-month follow-up.246,247 This is
supported by data from another study.248 Other agents that might be
effective for the prevention of BCC in individuals at high risk for
developing NMSCs include celecoxib,249 acitretin,250 capecitabine,251
and tazarotene.252

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-9
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Systemic Therapy size of existing lesions and the number of surgeries needed to remove
For local, high-risk BCC, systemic therapy is recommended after BCC lesions.260-262
positive margin with Mohs or other forms of PDEMA, for residual
Sonidegib is another HHI FDA-approved for the treatment of patients
disease after multiple resections (with Mohs or other forms of PDEMA
with laBCC that has recurred following surgery or RT, or who are not
or standard excision), or as primary treatment if curative RT and/or
candidates for surgery or RT.263 Sonidegib is not FDA approved for
curative surgery is not feasible. The indication for systemic therapy is
mBCC. 42-month follow-up data from the phase II BOLT trial reported
also extended to recurrent BCC after surgery, locally advanced (laBCC)
similar ORRs for the two doses tested among patients with laBCC.264-268
or metastatic BCC (mBCC) where topical therapy, surgery, or RT is
As with vismodegib, nearly all patients experienced at least one AE, and
unlikely to be curative. The systemic therapy options for BCC include
the most common AEs were muscle spasms, dysgeusia, alopecia,
hedgehog pathway inhibitor (HHI) and immunotherapy.
nausea, weight decrease, and fatigue. Elevated creatinine kinase was
Vismodegib is an HHI approved by the U.S. Food and Drug also frequently observed and was one of the most common grade 3–4
Administration (FDA) for the treatment of adults with laBCC or mBCC AEs, along with elevated lipase.
that has recurred following surgery, or those who are not candidates for
A key limitation to HHI therapies is that advanced BCC can develop
surgery or RT.253 39-month follow-up data from the ERIVANCE trial, a
resistance, which limits the duration of response. A small investigator-
multicenter phase II trial enrolling 104 patients reported an objective
initiated trial in patients with vismodegib-resistant advanced BCC
response rate (ORR) of 48.5% in the mBCC group and 60.3% in the
observed no responses during treatment with sonidegib for a median of
laBCC group, with a median duration of response of 14.8 months and
6 weeks (range, 3–58 weeks), and 5 of 9 patients progressed.269
26.2 months for each group, respectively.254-257 Results from other
Results from systematic reviews and meta-analyses on HHI in BCC are
clinical trials testing vismodegib in BCC are summarized in Table 2.
summarized in Table 2.
According to these data, nearly all patients treated with vismodegib
experienced at least one treatment-emergent adverse event (TEAE), Ongoing clinical research is exploring various dosing regimens of
but a significant proportion of these were low grade (grade ≤2).256,258,259 vismodegib and sonidegib in a variety of BCC treatment settings,
Serious AEs (SAEs) occurred in 25% to 32% of patients in these including in the neoadjuvant setting, in patients with multiple BCCs, in
studies. The most common AEs included muscle spasms, alopecia, patients with radiation-induced multiple BCCs of the scalp, as
taste loss, weight loss, decreased appetite, fatigue, nausea, and maintenance therapy after laBCC complete remission.270-275 Notably, in
diarrhea. the neoadjuvant setting, while one trial reported negative results (unmet
predefined complete histologic clearance rate),271 results from two
Vismodegib has also been tested as BCC treatment and prophylaxis in
studies indicated vismodegib may reduce surgical defect area and allow
patients with nevoid BCC syndrome. A randomized phase II study in
for downstaging of the surgical procedure for laBCCs in functionally
patients with nevoid BCC syndrome and at least 10 operable BCC
sensitive locations.270,273 However, all of these studies included small
lesions found that vismodegib significantly reduced incidence of new
BCC lesions compared with placebo, and also significantly reduced the
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-10
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
numbers of patients, and thus their results need to be carefully Cemiplimab-rwlc is an anti-PD-1 immunotherapy FDA-approved for
interpreted. patients with laBCC or mBCC previously treated with an HHI or for
whom an HHI is not appropriate.278 Results from a phase II trial testing
Other HHIs are also being tested in patients with BCC to see if they can cemiplimab-rwlc (N = 84) with a median follow-up of 15 months reported
provide higher rates of response, more durable responses, responses in an ORR of 31% and grade 3-4 TEAEs in 48% of patients. SAEs
less advanced BCC, or responses in BCC resistant to vismodegib. occurred in 35% of patients.279
Results from phase I–II trials with small BCC sample sizes (N < 40)
have shown that itraconazole and saridegib can elicit responses in Due to the rarity of advanced cases, the literature on chemotherapy for
patients with BCC, although not in patients who previously received BCC is limited to case reports.280-286
vismodegib.276,277

Table 2. Hedgehog Pathway Inhibitors in Advanced BCCa


Patients, n Objective Duration of Progression-free Overall Survival,
Study
Txb Response Rated Response, Medianc Survival, Medianc Medianc
Name and References Design laBCC mBCC laBCC mBCC laBCC mBCC laBCC mBCC laBCC mBCC
ERIVANCE – 39-month follow-up Phase II
Vismo 63 33 60% 49% 26.2 14.8 12.9 9.3 NE 33.4
NCT00833417254-257 OL
STEVIE – 12-month follow-up Phase II
Vismo 1077 84 69% 37% 23.0 13.9 23.2 13.1 NR NR
NCT01367665259,287,288 OL
NCT01160250258, e Phase II
Vismo 56 39 46% 31% NR NR NR NR NR NR
OL
RegiSONIC
Obs Vismo 66 – 68% – 5.95 – NE – NR –
NCT01604252289, f
BOLT – 42-month follow-up Phase II Soni 200 mg 66 13 56% 8% 26.1 24.0 22.1 13.1 NR NR
NCT01327053264-268 RDB Soni 800 mg 128 23 46% 17% 23.3 NE 24.9 11.1 NR NR
Systematic
Jacobsen et al290 Vismo 704 65% 34%
review
Systematic Vismo 69% 39%
Xie et al291 1102
review Soni 57% 15%
laBCC, locally advanced BCC; mBCC, metastatic BCC; NE, not reached; NR, not reported; Obs, prospective observational; OL, open-label; RDB, randomized double-blind; Soni, sonidegib; Tx,
treatment; Vismo, vismodegib.
aTrials included patients with advanced BCC that was inappropriate for surgery or RT.
bInhibitors were taken orally once daily. Vismodegib dose was 150 mg.
cTimes are reported in months.
dResponse criteria varied between studies.
eTrial was terminated early due to FDA approval of vismodegib.
fTrial was terminated early by the sponsor due to the high rate of discontinuation of subjects unrelated to patient safety.

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-11
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Follow-up cemiplimab-rwlc (as indicated in the previous section), or clinical trial
Follow-up for BCC should include history and physical examination, enrollment. For distant metastases, multidisciplinary consultation should
including complete skin examination every 6 to 12 months for the first 5 take place to consider one or more of the following options: vismodegib
years, and then at least annually for life. Imaging may be considered if or cemiplimab-rwlc (as indicated in the previous section), RT or surgery
clinical examination is insufficient for following the disease. Imaging for limited metastatic disease, or palliation and best supportive care.
modality and targeted area should be at the discretion of the treating
An estimated 30% to 50% of patients with BCC will develop another
team based on the suspected extent of disease (ie, local, regional,
BCC within 5 years.124,129,292-295 This represents a 10-fold increase in risk
metastatic). Histologic confirmation is often sufficient to diagnose local
compared to the general population.293 Patients with a prior BCC are
recurrence, but imaging can be considered to assess extent of disease.
also at increased risk of developing SCC and cutaneous
As part of follow-up, the patients should be educated on sun protection
melanoma.124,295 A prospective population-based cohort study found
and self-examination. For local recurrence, the primary treatment
that development of a second BCC is most likely during the short-term
pathway for local, high-risk BCC should be followed. For primary and
follow-up period after diagnosis of the first lesion.128 Therefore, close
recurrent nodal metastases, multidisciplinary consultation should take
follow-up of patients with BCC in both the short- and long-term is
place to consider one or more of the following options: surgery, HHI or
critical.

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-12
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
References Acad Dermatol 1984;10:1043-1060. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/6736323.
1. Asgari MM, Moffet HH, Ray GT, Quesenberry CP. Trends in basal
cell carcinoma incidence and identification of high-risk subgroups, 9. Nguyen-Nielsen M, Wang L, Pedersen L, et al. The incidence of
1998-2012. JAMA Dermatol 2015;151:976-981. Available at: metastatic basal cell carcinoma (mBCC) in Denmark, 1997-2010. Eur
http://www.ncbi.nlm.nih.gov/pubmed/26039887. J Dermatol 2015;25:463-468. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/26105129.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J
Clin 2016;66:7-30. Available at: 10. Wadhera A, Fazio M, Bricca G, Stanton O. Metastatic basal cell
https://www.ncbi.nlm.nih.gov/pubmed/26742998. carcinoma: a case report and literature review. How accurate is our
incidence data? Dermatol Online J 2006;12:7. Available at:
3. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence
https://www.ncbi.nlm.nih.gov/pubmed/16962022.
estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in
the U.S. population, 2012. JAMA Dermatol 2015;151:1081-1086. 11. Kricker A, Armstrong BK, English DR, Heenan PJ. Does
Available at: http://www.ncbi.nlm.nih.gov/pubmed/25928283. intermittent sun exposure cause basal cell carcinoma? a case-control
study in Western Australia. Int J Cancer 1995;60:489-494. Available
4. Abbas M, Kalia S. Trends in non-melanoma skin cancer (basal cell
at: http://www.ncbi.nlm.nih.gov/pubmed/7829262.
carcinoma and squamous cell carcinoma) in Canada: a descriptive
analysis of available data. J Cutan Med Surg 2016;20:166-175. 12. Kricker A, Armstrong BK, English DR, Heenan PJ. A dose-
Available at: http://www.ncbi.nlm.nih.gov/pubmed/26458408. response curve for sun exposure and basal cell carcinoma. Int J
Cancer 1995;60:482-488. Available at:
5. Rudolph C, Schnoor M, Eisemann N, Katalinic A. Incidence trends
http://www.ncbi.nlm.nih.gov/pubmed/7829261.
of nonmelanoma skin cancer in Germany from 1998 to 2010. J Dtsch
Dermatol Ges 2015;13:788-797. Available at: 13. Zanetti R, Rosso S, Martinez C, et al. Comparison of risk patterns
http://www.ncbi.nlm.nih.gov/pubmed/26213814. in carcinoma and melanoma of the skin in men: a multi-centre case-
case-control study. Br J Cancer 2006;94:743-751. Available at:
6. Muzic JG, Schmitt AR, Wright AC, et al. Incidence and Trends of
http://www.ncbi.nlm.nih.gov/pubmed/16495934.
Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma: A
Population-Based Study in Olmsted County, Minnesota, 2000 to 2010. 14. Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure,
Mayo Clin Proc 2017;92:890-898. Available at: pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal
https://www.ncbi.nlm.nih.gov/pubmed/28522111. cell carcinoma. Arch Dermatol 1995;131:157-163. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/7857111.
7. Christenson LJ, Borrowman TA, Vachon CM, et al. Incidence of
basal cell and squamous cell carcinomas in a population younger than 15. Ramsay HM, Fryer AA, Hawley CM, et al. Factors associated with
40 years. JAMA 2005;294:681-690. Available at: nonmelanoma skin cancer following renal transplantation in
http://www.ncbi.nlm.nih.gov/pubmed/16091570. Queensland, Australia. J Am Acad Dermatol 2003;49:397-406.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/12963901.
8. von Domarus H, Stevens PJ. Metastatic basal cell carcinoma.
Report of five cases and review of 170 cases in the literature. J Am 16. Kaskel P, Lange U, Sander S, et al. Ultraviolet exposure and risk
of melanoma and basal cell carcinoma in Ulm and Dresden, Germany.
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-13
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
J Eur Acad Dermatol Venereol 2015;29:134-142. Available at: 24. Karagas MR, Nelson HH, Zens MS, et al. Squamous cell and
http://www.ncbi.nlm.nih.gov/pubmed/24684198. basal cell carcinoma of the skin in relation to radiation therapy and
potential modification of risk by sun exposure. Epidemiology
17. Khalesi M, Whiteman DC, Tran B, et al. A meta-analysis of 2007;18:776-784. Available at:
pigmentary characteristics, sun sensitivity, freckling and melanocytic https://www.ncbi.nlm.nih.gov/pubmed/17917604.
nevi and risk of basal cell carcinoma of the skin. Cancer Epidemiol
2013;37:534-543. Available at: 25. Watt TC, Inskip PD, Stratton K, et al. Radiation-related risk of
http://www.ncbi.nlm.nih.gov/pubmed/23849507. basal cell carcinoma: a report from the Childhood Cancer Survivor
Study. J Natl Cancer Inst 2012;104:1240-1250. Available at:
18. Walther U, Kron M, Sander S, et al. Risk and protective factors for http://www.ncbi.nlm.nih.gov/pubmed/22835387.
sporadic basal cell carcinoma: results of a two-centre case-control
study in southern Germany. Clinical actinic elastosis may be a 26. Schwartz JL, Kopecky KJ, Mathes RW, et al. Basal cell skin
protective factor. Br J Dermatol 2004;151:170-178. Available at: cancer after total-body irradiation and hematopoietic cell
http://www.ncbi.nlm.nih.gov/pubmed/15270887. transplantation. Radiat Res 2009;171:155-163. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/19267540.
19. Box NF, Duffy DL, Irving RE, et al. Melanocortin-1 receptor
genotype is a risk factor for basal and squamous cell carcinoma. J 27. Karagas MR, McDonald JA, Greenberg ER, et al. Risk of basal cell
Invest Dermatol 2001;116:224-229. Available at: and squamous cell skin cancers after ionizing radiation therapy. For
http://www.ncbi.nlm.nih.gov/pubmed/11179997. The Skin Cancer Prevention Study Group. J Natl Cancer Inst
1996;88:1848-1853. Available at:
20. Lock-Andersen J, Drzewiecki KT, Wulf HC. Eye and hair colour, http://www.ncbi.nlm.nih.gov/pubmed/8961975.
skin type and constitutive skin pigmentation as risk factors for basal
cell carcinoma and cutaneous malignant melanoma. A Danish case- 28. PubMed Overview. Available at:
control study. Acta Derm Venereol 1999;79:74-80. Available at: https://pubmed.ncbi.nlm.nih.gov/about/. Accessed November 15th,
http://www.ncbi.nlm.nih.gov/pubmed/10086866. 2021.

21. Chinem VP, Miot HA. Prevalence of actinic skin lesions in patients 29. Lesiak A, Sobolewska-Sztychny D, Majak P, et al. Relation
with basal cell carcinoma of the head: a case-control study. Rev Assoc between sonic hedgehog pathway gene polymorphisms and basal cell
Med Bras 2012;58:188-196. Available at: carcinoma development in the Polish population. Arch Dermatol Res
http://www.ncbi.nlm.nih.gov/pubmed/22569613. 2016;308:39-47. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/26590974.
22. Wu S, Han J, Li WQ, et al. Basal-cell carcinoma incidence and
associated risk factors in U.S. women and men. Am J Epidemiol 30. Reifenberger J, Wolter M, Weber RG, et al. Missense mutations in
2013;178:890-897. Available at: SMOH in sporadic basal cell carcinomas of the skin and primitive
https://www.ncbi.nlm.nih.gov/pubmed/23828250. neuroectodermal tumors of the central nervous system. Cancer Res
1998;58:1798-1803. Available at:
23. Perkins JL, Liu Y, Mitby PA, et al. Nonmelanoma skin cancer in http://www.ncbi.nlm.nih.gov/pubmed/9581815.
survivors of childhood and adolescent cancer: a report from the
childhood cancer survivor study. J Clin Oncol 2005;23:3733-3741.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/15923570.
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-14
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
31. Xie J, Murone M, Luoh SM, et al. Activating Smoothened 39. Gailani MR, Stahle-Backdahl M, Leffell DJ, et al. The role of the
mutations in sporadic basal-cell carcinoma. Nature 1998;391:90-92. human homologue of Drosophila patched in sporadic basal cell
Available at: http://www.ncbi.nlm.nih.gov/pubmed/9422511. carcinomas. Nat Genet 1996;14:78-81. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/8782823.
32. Gailani MR, Bale SJ, Leffell DJ, et al. Developmental defects in
Gorlin syndrome related to a putative tumor suppressor gene on 40. Zhang H, Ping XL, Lee PK, et al. Role of PTCH and p53 genes in
chromosome 9. Cell 1992;69:111-117. Available at: early-onset basal cell carcinoma. Am J Pathol 2001;158:381-385.
http://www.ncbi.nlm.nih.gov/pubmed/1348213. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11159175.

33. Soufir N, Gerard B, Portela M, et al. PTCH mutations and 41. Ziegler A, Leffell DJ, Kunala S, et al. Mutation hotspots due to
deletions in patients with typical nevoid basal cell carcinoma syndrome sunlight in the p53 gene of nonmelanoma skin cancers. Proc Natl
and in patients with a suspected genetic predisposition to basal cell Acad Sci U S A 1993;90:4216-4220. Available at:
carcinoma: a French study. Br J Cancer 2006;95:548-553. Available http://www.ncbi.nlm.nih.gov/pubmed/8483937.
at: http://www.ncbi.nlm.nih.gov/pubmed/16909134.
42. Oluwasanmi JO, Williams AO, Alli AF. Superficial cancer in
34. Ling G, Ahmadian A, Persson A, et al. PATCHED and p53 gene Nigeria. Br J Cancer 1969;23:714-728. Available at:
alterations in sporadic and hereditary basal cell cancer. Oncogene http://www.ncbi.nlm.nih.gov/pubmed/5367332.
2001;20:7770-7778. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/11753655. 43. Yakubu A, Mabogunje OA. Skin cancer in Zaria, Nigeria. Trop
Doct 1995;25 Suppl 1:63-67. Available at:
35. Heitzer E, Lassacher A, Quehenberger F, et al. UV fingerprints http://www.ncbi.nlm.nih.gov/pubmed/7879275.
predominate in the PTCH mutation spectra of basal cell carcinomas
independent of clinical phenotype. J Invest Dermatol 2007;127:2872- 44. Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum.
2881. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17597822. Cutaneous, ocular, and neurologic abnormalities in 830 published
cases. Arch Dermatol 1987;123:241-250. Available at:
36. Danaee H, Karagas MR, Kelsey KT, et al. Allelic loss at Drosophila http://www.ncbi.nlm.nih.gov/pubmed/3545087.
patched gene is highly prevalent in Basal and squamous cell
carcinomas of the skin. J Invest Dermatol 2006;126:1152-1158. 45. Bradford PT, Goldstein AM, Tamura D, et al. Cancer and
Available at: http://www.ncbi.nlm.nih.gov/pubmed/16484983. neurologic degeneration in xeroderma pigmentosum: long term follow-
up characterises the role of DNA repair. J Med Genet 2011;48:168-
37. Reifenberger J, Wolter M, Knobbe CB, et al. Somatic mutations in 176. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21097776.
the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell
carcinomas. Br J Dermatol 2005;152:43-51. Available at: 46. Kraemer KH, Lee MM, Andrews AD, Lambert WC. The role of
http://www.ncbi.nlm.nih.gov/pubmed/15656799. sunlight and DNA repair in melanoma and nonmelanoma skin cancer.
The xeroderma pigmentosum paradigm. Arch Dermatol
38. Kim MY, Park HJ, Baek SC, et al. Mutations of the p53 and PTCH 1994;130:1018-1021. Available at:
gene in basal cell carcinomas: UV mutation signature and strand bias. http://www.ncbi.nlm.nih.gov/pubmed/8053698.
J Dermatol Sci 2002;29:1-9. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/12007715. 47. Kraemer KH, Lee MM, Scotto J. DNA repair protects against
cutaneous and internal neoplasia: evidence from xeroderma
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-15
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
pigmentosum. Carcinogenesis 1984;5:511-514. Available at: surgery. Head Neck 2011;33:469-475. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/6705149. http://www.ncbi.nlm.nih.gov/pubmed/20645285.

48. Couve-Privat S, Le Bret M, Traiffort E, et al. Functional analysis of 55. Williams LS, Mancuso AA, Mendenhall WM. Perineural spread of
novel sonic hedgehog gene mutations identified in basal cell cutaneous squamous and basal cell carcinoma: CT and MR detection
carcinomas from xeroderma pigmentosum patients. Cancer Res and its impact on patient management and prognosis. Int J Radiat
2004;64:3559-3565. Available at: Oncol Biol Phys 2001;49:1061-1069. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/15150112. http://www.ncbi.nlm.nih.gov/pubmed/11240248.

49. Couve-Privat S, Bouadjar B, Avril MF, et al. Significantly high 56. Boeta-Angeles L, Bennett RG. Features associated with
levels of ultraviolet-specific mutations in the smoothened gene in basal recurrence (basal cell carcinoma). In: Miller SJ, Maloney ME, eds.
cell carcinomas from DNA repair-deficient xeroderma pigmentosum Cutaneous Oncology Pathophysiology, diagnosis, and management.
patients. Cancer Res 2002;62:7186-7189. Available at: Malden, MA: Blackwell Science; 1998:646-656.
http://www.ncbi.nlm.nih.gov/pubmed/12499255.
57. Silverman MK, Kopf AW, Bart RS, et al. Recurrence rates of
50. Miller KL, Karagas MR, Kraft P, et al. XPA, haplotypes, and risk of treated basal cell carcinomas. Part 3: Surgical excision. J Dermatol
basal and squamous cell carcinoma. Carcinogenesis 2006;27:1670- Surg Oncol 1992;18:471-476. Available at:
1675. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16513681. http://www.ncbi.nlm.nih.gov/pubmed/1592998.

51. Chen J, Ruczinski I, Jorgensen TJ, et al. Nonmelanoma skin 58. Silverman MK, Kopf AW, Grin CM, et al. Recurrence rates of
cancer and risk for subsequent malignancy. J Natl Cancer Inst treated basal cell carcinomas. Part 2: Curettage-electrodesiccation. J
2008;100:1215-1222. Available at: Dermatol Surg Oncol 1991;17:720-726. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/18728282. http://www.ncbi.nlm.nih.gov/pubmed/1820764.

52. Clements S, Khachemoune A. Upstaging of basal cell and 59. Dubin N, Kopf AW. Multivariate risk score for recurrence of
squamous cell carcinomas during definitive surgery: a review of cutaneous basal cell carcinomas. Arch Dermatol 1983;119:373-377.
predictive preoperative clinical and histologic features. Arch Dermatol Available at: http://www.ncbi.nlm.nih.gov/pubmed/6847215.
Res 2021;313:319-325. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/33108525. 60. Bogelund FS, Philipsen PA, Gniadecki R. Factors affecting the
recurrence rate of basal cell carcinoma. Acta Derm Venereol
53. Singh B, Dorelles A, Konnikov N, Nguyen BM. Detection of High- 2007;87:330-334. Available at:
Risk Histologic Features and Tumor Upstaging of Nonmelanoma Skin http://www.ncbi.nlm.nih.gov/pubmed/17598036.
Cancers on Debulk Analysis: A Quantitative Systematic Review.
Dermatol Surg 2017;43:1003-1011. Available at: 61. Rigel DS, Robins P, Friedman RJ. Predicting recurrence of basal-
https://www.ncbi.nlm.nih.gov/pubmed/28654579. cell carcinomas treated by microscopically controlled excision: a
recurrence index score. J Dermatol Surg Oncol 1981;7:807-810.
54. Gandhi MR, Panizza B, Kennedy D. Detecting and defining the Available at: http://www.ncbi.nlm.nih.gov/pubmed/7298981.
anatomic extent of large nerve perineural spread of malignancy:
comparing "targeted" MRI with the histologic findings following

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-16
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
62. Spiller WF, Spiller RF. Treatment of basal cell epithelioma by 70. Codazzi D, Van Der Velden J, Carminati M, et al. Positive
curettage and electrodesiccation. J Am Acad Dermatol 1984;11:808- compared with negative margins in a single-centre retrospective study
814. Available at: http://www.ncbi.nlm.nih.gov/pubmed/6512037. on 3957 consecutive excisions of basal cell carcinomas. Associated
risk factors and preferred surgical management. J Plast Surg Hand
63. van Iersel CA, van de Velden HV, Kusters CD, et al. Prognostic Surg 2014;48:38-43. Available at:
factors for a subsequent basal cell carcinoma: implications for follow- http://www.ncbi.nlm.nih.gov/pubmed/23731130.
up. Br J Dermatol 2005;153:1078-1080. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/16225637. 71. Krynitz B, Olsson H, Lundh Rozell B, et al. Risk of basal cell
carcinoma in Swedish organ transplant recipients: a population-based
64. Petrovich Z, Kuisk H, Langholz B, et al. Treatment results and study. Br J Dermatol 2016;174:95-103. Available at:
patterns of failure in 646 patients with carcinoma of the eyelids, pinna, http://www.ncbi.nlm.nih.gov/pubmed/26333521.
and nose. Am J Surg 1987;154:447-450. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/3661851. 72. Mackintosh LJ, Geddes CC, Herd RM. Skin tumours in the West of
Scotland renal transplant population. Br J Dermatol 2013;168:1047-
65. Silverman MK, Kopf AW, Grin CM, et al. Recurrence rates of 1053. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23137036.
treated basal cell carcinomas. Part 1: Overview. J Dermatol Surg
Oncol 1991;17:713-718. Available at: 73. Bernat Garcia J, Morales Suarez-Varela M, Vilata JJ, et al. Risk
http://www.ncbi.nlm.nih.gov/pubmed/1890243. factors for non-melanoma skin cancer in kidney transplant patients in
a Spanish population in the Mediterranean region. Acta Derm
66. Connolly AH, Baker DR, Coldiron BM, et al. Venereol 2013;93:422-427. Available at:
AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for mohs http://www.ncbi.nlm.nih.gov/pubmed/23303600.
micrographic surgery: a report of the American Academy of
Dermatology, American College of Mohs Surgery, American Society 74. Karczewski M, Stronka M, Karczewski J, Wiktorowicz K. Skin
for Dermatologic Surgery Association, and the American Society for cancer following kidney transplantation: a single-center experience.
Mohs Surgery. Dermatol Surg 2012;38:1582-1603. Available at: Transplant Proc 2011;43:3760-3761. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/22958088. http://www.ncbi.nlm.nih.gov/pubmed/22172842.

67. Dixon AY, Lee SH, McGregor DH. Histologic features predictive of 75. Bordea C, Wojnarowska F, Millard PR, et al. Skin cancers in renal-
basal cell carcinoma recurrence: results of a multivariate analysis. J transplant recipients occur more frequently than previously recognized
Cutan Pathol 1993;20:137-142. Available at: in a temperate climate. Transplantation 2004;77:574-579. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/8320358. http://www.ncbi.nlm.nih.gov/pubmed/15084938.

68. Jacobs GH, Rippey JJ, Altini M. Prediction of aggressive behavior 76. DePry JL, Vyas R, Lazarus HM, et al. Cutaneous malignant
in basal cell carcinoma. Cancer 1982;49:533-537. Available at: neoplasms in hematopoietic cell transplant recipients: a systematic
http://www.ncbi.nlm.nih.gov/pubmed/7059912. review. JAMA Dermatol 2015;151:775-782. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/25902409.
69. de Rosa G, Vetrani A, Zeppa P, et al. Comparative morphometric
analysis of aggressive and ordinary basal cell carcinoma of the skin. 77. Stern RS, Liebman EJ, Vakeva L. Oral psoralen and ultraviolet-A
Cancer 1990;65:544-549. Available at: light (PUVA) treatment of psoriasis and persistent risk of
http://www.ncbi.nlm.nih.gov/pubmed/2297645. nonmelanoma skin cancer. PUVA Follow-up Study. J Natl Cancer Inst
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-17
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
1998;90:1278-1284. Available at: 85. Fortina AB, Piaserico S, Caforio AL, et al. Immunosuppressive
http://www.ncbi.nlm.nih.gov/pubmed/9731734. level and other risk factors for basal cell carcinoma and squamous cell
carcinoma in heart transplant recipients. Arch Dermatol
78. Archier E, Devaux S, Castela E, et al. Carcinogenic risks of 2004;140:1079-1085. Available at:
psoralen UV-A therapy and narrowband UV-B therapy in chronic http://www.ncbi.nlm.nih.gov/pubmed/15381547.
plaque psoriasis: a systematic literature review. J Eur Acad Dermatol
Venereol 2012;26 Suppl 3:22-31. Available at: 86. Kanitakis J, Alhaj-Ibrahim L, Euvrard S, Claudy A. Basal cell
http://www.ncbi.nlm.nih.gov/pubmed/22512677. carcinomas developing in solid organ transplant recipients:
clinicopathologic study of 176 cases. Arch Dermatol 2003;139:1133-
79. Park GH, Chang SE, Won CH, et al. Incidence of primary skin 1137. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12975154.
cancer after organ transplantation: An 18-year single-center
experience in Korea. J Am Acad Dermatol 2014;70:465-472. Available 87. Harwood CA, Proby CM, McGregor JM, et al. Clinicopathologic
at: http://www.ncbi.nlm.nih.gov/pubmed/24342756. features of skin cancer in organ transplant recipients: a retrospective
case-control series. J Am Acad Dermatol 2006;54:290-300. Available
80. Jensen AO, Svaerke C, Farkas D, et al. Skin cancer risk among at: http://www.ncbi.nlm.nih.gov/pubmed/16443060.
solid organ recipients: a nationwide cohort study in Denmark. Acta
Derm Venereol 2010;90:474-479. Available at: 88. Lott DG, Manz R, Koch C, Lorenz RR. Aggressive behavior of
http://www.ncbi.nlm.nih.gov/pubmed/20814621. nonmelanotic skin cancers in solid organ transplant recipients.
Transplantation 2010;90:683-687. Available at:
81. Hartevelt MM, Bavinck JN, Kootte AM, et al. Incidence of skin http://www.ncbi.nlm.nih.gov/pubmed/20808266.
cancer after renal transplantation in The Netherlands. Transplantation
1990;49:506-509. Available at: 89. Martin H, Strong E, Spiro RH. Radiation-induced skin cancer of the
http://www.ncbi.nlm.nih.gov/pubmed/2316011. head and neck. Cancer 1970;25:61-71. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/4312028.
82. Harwood CA, Mesher D, McGregor JM, et al. A surveillance model
for skin cancer in organ transplant recipients: a 22-year prospective 90. Lichter MD, Karagas MR, Mott LA, et al. Therapeutic ionizing
study in an ethnically diverse population. Am J Transplant radiation and the incidence of basal cell carcinoma and squamous cell
2013;13:119-129. Available at: carcinoma. The New Hampshire Skin Cancer Study Group. Arch
http://www.ncbi.nlm.nih.gov/pubmed/23072567. Dermatol 2000;136:1007-1011. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/10926736.
83. Brewer JD, Colegio OR, Phillips PK, et al. Incidence of and risk
factors for skin cancer after heart transplant. Arch Dermatol 91. Dixon AY, Lee SH, McGregor DH. Factors predictive of recurrence
2009;145:1391-1396. Available at: of basal cell carcinoma. Am J Dermatopathol 1989;11:222-232.
http://www.ncbi.nlm.nih.gov/pubmed/20026847. Available at: http://www.ncbi.nlm.nih.gov/pubmed/2729527.

84. Rashtak S, Dierkhising RA, Kremers WK, et al. Incidence and risk 92. Smeets NW, Kuijpers DI, Nelemans P, et al. Mohs' micrographic
factors for skin cancer following lung transplantation. J Am Acad surgery for treatment of basal cell carcinoma of the face--results of a
Dermatol 2015;72:92-98. Available at: retrospective study and review of the literature. Br J Dermatol
https://www.ncbi.nlm.nih.gov/pubmed/25440431. 2004;151:141-147. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/15270883.
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-18
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
93. Cigna E, Tarallo M, Maruccia M, et al. Basal cell carcinoma: 10 101. Wermker K, Roknic N, Goessling K, et al. Basosquamous
years of experience. J Skin Cancer 2011;2011:476362. Available at: carcinoma of the head and neck: clinical and histologic characteristics
http://www.ncbi.nlm.nih.gov/pubmed/21151696. and their impact on disease progression. Neoplasia 2015;17:301-305.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/25810014.
94. Szewczyk MP, Pazdrowski J, Danczak-Pazdrowska A, et al.
Analysis of selected recurrence risk factors after treatment of head 102. Hassanein AM, Proper SA, Depcik-Smith ND, Flowers FP.
and neck basal cell carcinoma. Postepy Dermatol Alergol Peritumoral fibrosis in basal cell and squamous cell carcinoma
2014;31:146-151. Available at: mimicking perineural invasion: potential pitfall in Mohs micrographic
http://www.ncbi.nlm.nih.gov/pubmed/25097485. surgery. Dermatol Surg 2005;31:1101-1106. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/16164857.
95. Bartos V, Pokorny D, Zacharova O, et al. Recurrent basal cell
carcinoma: a clinicopathological study and evaluation of 103. Lin C, Tripcony L, Keller J, et al. Perineural infiltration of
histomorphological findings in primary and recurrent lesions. Acta cutaneous squamous cell carcinoma and basal cell carcinoma without
Dermatovenerol Alp Pannonica Adriat 2011;20:67-75. Available at: clinical features. Int J Radiat Oncol Biol Phys 2012;82:334-340.
http://www.ncbi.nlm.nih.gov/pubmed/21993704. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21093171.

96. Sartore L, Lancerotto L, Salmaso M, et al. Facial basal cell 104. Garcia-Serra A, Hinerman RW, Mendenhall WM, et al.
carcinoma: analysis of recurrence and follow-up strategies. Oncol Rep Carcinoma of the skin with perineural invasion. Head Neck
2011;26:1423-1429. Available at: 2003;25:1027-1033. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/21922143. http://www.ncbi.nlm.nih.gov/pubmed/14648861.

97. Sloane JP. The value of typing basal cell carcinomas in predicting 105. Lin C, Tripcony L, Keller J, et al. Cutaneous carcinoma of the
recurrence after surgical excision. Br J Dermatol 1977;96:127-132. head and neck with clinical features of perineural infiltration treated
Available at: http://www.ncbi.nlm.nih.gov/pubmed/843446. with radiotherapy. Clin Oncol (R Coll Radiol) 2013;25:362-367.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/23489870.
98. Costantino D, Lowe L, Brown DL. Basosquamous carcinoma-an
under-recognized, high-risk cutaneous neoplasm: case study and 106. Leibovitch I, Huilgol SC, Selva D, et al. Basal cell carcinoma
review of the literature. J Plast Reconstr Aesthet Surg 2006;59:424- treated with Mohs surgery in Australia III. Perineural invasion. J Am
428. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16756261. Acad Dermatol 2005;53:458-463. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/16112353.
99. Martin RC, 2nd, Edwards MJ, Cawte TG, et al. Basosquamous
carcinoma: analysis of prognostic factors influencing recurrence. 107. Jackson JE, Dickie GJ, Wiltshire KL, et al. Radiotherapy for
Cancer 2000;88:1365-1369. Available at: perineural invasion in cutaneous head and neck carcinomas: toward a
http://www.ncbi.nlm.nih.gov/pubmed/10717618. risk-adapted treatment approach. Head Neck 2009;31:604-610.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/19132719.
100. Garcia C, Poletti E, Crowson AN. Basosquamous carcinoma. J
Am Acad Dermatol 2009;60:137-143. Available at: 108. Ratner D, Lowe L, Johnson TM, Fader DJ. Perineural spread of
http://www.ncbi.nlm.nih.gov/pubmed/19103364. basal cell carcinomas treated with Mohs micrographic surgery. Cancer
2000;88:1605-1613. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/10738219.
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-19
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
109. Brown CI, Perry AE. Incidence of perineural invasion in subtype. Br J Dermatol 2002;147:41-47. Available at:
histologically aggressive types of basal cell carcinoma. Am J http://www.ncbi.nlm.nih.gov/pubmed/12100183.
Dermatopathol 2000;22:123-125. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/10770431. 117. Raasch BA, Buettner PG, Garbe C. Basal cell carcinoma:
histological classification and body-site distribution. Br J Dermatol
110. Galloway TJ, Morris CG, Mancuso AA, et al. Impact of 2006;155:401-407. Available at:
radiographic findings on prognosis for skin carcinoma with clinical http://www.ncbi.nlm.nih.gov/pubmed/16882181.
perineural invasion. Cancer 2005;103:1254-1257. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/15693020. 118. Dinehart SM, Dodge R, Stanley WE, et al. Basal cell carcinoma
treated with Mohs surgery. A comparison of 54 younger patients with
111. Balamucki CJ, DeJesus R, Galloway TJ, et al. Impact of 1050 older patients. J Dermatol Surg Oncol 1992;18:560-566.
radiographic findings on for prognosis skin cancer with perineural Available at: http://www.ncbi.nlm.nih.gov/pubmed/1624629.
invasion. Am J Clin Oncol 2015;38:248-251. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/23648439. 119. Milroy CJ, Horlock N, Wilson GD, Sanders R. Aggressive basal
cell carcinoma in young patients: fact or fiction? Br J Plast Surg
112. Cernea CR, Ferraz AR, de Castro IV, et al. Perineural invasion in 2000;53:393-396. Available at:
aggressive skin carcinomas of the head and neck. Potentially http://www.ncbi.nlm.nih.gov/pubmed/10876275.
dangerous but frequently overlooked. ORL J Otorhinolaryngol Relat
Spec 2009;71:21-26. Available at: 120. Roudier-Pujol C, Auperin A, Nguyen T, et al. Basal cell
http://www.ncbi.nlm.nih.gov/pubmed/18946230. carcinoma in young adults: not more aggressive than in older patients.
Dermatology 1999;199:119-123. Available at:
113. Leffell DJ, Headington JT, Wong DS, Swanson NA. Aggressive- http://www.ncbi.nlm.nih.gov/pubmed/10559576.
growth basal cell carcinoma in young adults. Arch Dermatol
1991;127:1663-1667. Available at: 121. Lear JT, Smith AG, Bowers B, et al. Truncal tumor site is
http://www.ncbi.nlm.nih.gov/pubmed/1952969. associated with high risk of multiple basal cell carcinoma and is
influenced by glutathione S-transferase, GSTT1, and cytochrome
114. McCormack CJ, Kelly JW, Dorevitch AP. Differences in age and P450, CYP1A1 genotypes, and their interaction. J Invest Dermatol
body site distribution of the histological subtypes of basal cell 1997;108:519-522. Available at:
carcinoma. A possible indicator of differing causes. Arch Dermatol http://www.ncbi.nlm.nih.gov/pubmed/9077484.
1997;133:593-596. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/9158412. 122. Ramachandran S, Fryer AA, Lovatt T, et al. The rate of increase
in the numbers of primary sporadic basal cell carcinomas during follow
115. Bastiaens MT, Hoefnagel JJ, Bruijn JA, et al. Differences in age, up is associated with age at first presentation. Carcinogenesis
site distribution, and sex between nodular and superficial basal cell 2002;23:2051-2054. Available at:
carcinoma indicate different types of tumors. J Invest Dermatol http://www.ncbi.nlm.nih.gov/pubmed/12507928.
1998;110:880-884. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/9620293. 123. Cheretis C, Angelidou E, Dietrich F, et al. Prognostic value of
computer-assisted morphological and morphometrical analysis for
116. Scrivener Y, Grosshans E, Cribier B. Variations of basal cell detecting the recurrence tendency of basal cell carcinoma. Med Sci
carcinomas according to gender, age, location and histopathological
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-20
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Monit 2008;14:MT13-19. Available at: 131. Milan T, Pukkala E, Verkasalo PK, et al. Subsequent primary
http://www.ncbi.nlm.nih.gov/pubmed/18443558. cancers after basal-cell carcinoma: A nationwide study in Finland from
1953 to 1995. Int J Cancer 2000;87:283-288. Available at:
124. Karagas MR, Stukel TA, Greenberg ER, et al. Risk of subsequent http://www.ncbi.nlm.nih.gov/pubmed/10861488.
basal cell carcinoma and squamous cell carcinoma of the skin among
patients with prior skin cancer. Skin Cancer Prevention Study Group. 132. McCusker M, Basset-Seguin N, Dummer R, et al. Metastatic
JAMA 1992;267:3305-3310. Available at: basal cell carcinoma: prognosis dependent on anatomic site and
http://www.ncbi.nlm.nih.gov/pubmed/1597912. spread of disease. Eur J Cancer 2014;50:774-783. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/24412051.
125. Lovatt TJ, Lear JT, Bastrilles J, et al. Associations between
ultraviolet radiation, basal cell carcinoma site and histology, host 133. Rowe DE, Carroll RJ, Day CL, Jr. Long-term recurrence rates in
characteristics, and rate of development of further tumors. J Am Acad previously untreated (primary) basal cell carcinoma: implications for
Dermatol 2005;52:468-473. Available at: patient follow-up. J Dermatol Surg Oncol 1989;15:315-328. Available
http://www.ncbi.nlm.nih.gov/pubmed/15761425. at: http://www.ncbi.nlm.nih.gov/pubmed/2646336.

126. Levi F, Randimbison L, Maspoli M, et al. High incidence of 134. Barlow JO, Zalla MJ, Kyle A, et al. Treatment of basal cell
second basal cell skin cancers. Int J Cancer 2006;119:1505-1507. carcinoma with curettage alone. J Am Acad Dermatol 2006;54:1039-
Available at: http://www.ncbi.nlm.nih.gov/pubmed/16642479. 1045. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16713459.

127. Richmond-Sinclair NM, Pandeya N, Williams GM, et al. Clinical 135. Thissen MR, Neumann MH, Schouten LJ. A systematic review of
signs of photodamage are associated with basal cell carcinoma treatment modalities for primary basal cell carcinomas. Arch Dermatol
multiplicity and site: a 16-year longitudinal study. Int J Cancer 1999;135:1177-1183. Available at:
2010;127:2622-2629. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10522664.
http://www.ncbi.nlm.nih.gov/pubmed/20196068.
136. Chren MM, Torres JS, Stuart SE, et al. Recurrence after
128. Kiiski V, de Vries E, Flohil SC, et al. Risk factors for single and treatment of nonmelanoma skin cancer: a prospective cohort study.
multiple basal cell carcinomas. Arch Dermatol 2010;146:848-855. Arch Dermatol 2011;147:540-546. Available at:
Available at: http://www.ncbi.nlm.nih.gov/pubmed/20713815. https://www.ncbi.nlm.nih.gov/pubmed/21576572.

129. Flohil SC, Koljenovic S, de Haas ER, et al. Cumulative risks and 137. Julian C, Bowers PW, Pritchard C. A comparative study of the
rates of subsequent basal cell carcinomas in the Netherlands. Br J effects of disposable and Volkmann spoon curettes in the treatment of
Dermatol 2011;165:874-881. Available at: basal cell carcinoma. Br J Dermatol 2009;161:1407-1409. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/21711333. http://www.ncbi.nlm.nih.gov/pubmed/19681879.

130. Verkouteren JA, Smedinga H, Steyerberg EW, et al. Predicting 138. Blixt E, Nelsen D, Stratman E. Recurrence rates of aggressive
the risk of a second basal cell carcinoma. J Invest Dermatol histologic types of basal cell carcinoma after treatment with
2015;135:2649-2656. Available at: electrodesiccation and curettage alone. Dermatol Surg 2013;39:719-
http://www.ncbi.nlm.nih.gov/pubmed/26121210. 725. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23379543.

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-21
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
139. Rodriguez-Vigil T, Vazquez-Lopez F, Perez-Oliva N. Recurrence 147. Bisson MA, Dunkin CS, Suvarna SK, Griffiths RW. Do plastic
rates of primary basal cell carcinoma in facial risk areas treated with surgeons resect basal cell carcinomas too widely? A prospective study
curettage and electrodesiccation. J Am Acad Dermatol 2007;56:91-95. comparing surgical and histological margins. Br J Plast Surg
Available at: http://www.ncbi.nlm.nih.gov/pubmed/17190625. 2002;55:293-297. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/12160534.
140. Kopf AW, Bart RS, Schrager D, et al. Curettage-
electrodesiccation treatment of basal cell carcinomas. Arch Dermatol 148. Gulleth Y, Goldberg N, Silverman RP, Gastman BR. What is the
1977;113:439-443. Available at: best surgical margin for a Basal cell carcinoma: a meta-analysis of the
http://www.ncbi.nlm.nih.gov/pubmed/848972. literature. Plast Reconstr Surg 2010;126:1222-1231. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/20885244.
141. Rowe DE, Carroll RJ, Day CL, Jr. Mohs surgery is the treatment
of choice for recurrent (previously treated) basal cell carcinoma. J 149. Thomas DJ, King AR, Peat BG. Excision margins for
Dermatol Surg Oncol 1989;15:424-431. Available at: nonmelanotic skin cancer. Plast Reconstr Surg 2003;112:57-63.
http://www.ncbi.nlm.nih.gov/pubmed/2925988. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12832877.

142. Kuijpers DI, Thissen MR, Berretty PJ, et al. Surgical excision 150. Su SY, Giorlando F, Ek EW, Dieu T. Incomplete excision of basal
versus curettage plus cryosurgery in the treatment of basal cell cell carcinoma: a prospective trial. Plast Reconstr Surg
carcinoma. Dermatol Surg 2007;33:579-587. Available at: 2007;120:1240-1248. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/17451581. https://www.ncbi.nlm.nih.gov/pubmed/17898596.

143. Rhodes LE, de Rie MA, Leifsdottir R, et al. Five-year follow-up of 151. Farhi D, Dupin N, Palangie A, et al. Incomplete excision of basal
a randomized, prospective trial of topical methyl aminolevulinate cell carcinoma: rate and associated factors among 362 consecutive
photodynamic therapy vs surgery for nodular basal cell carcinoma. cases. Dermatol Surg 2007;33:1207-1214. Available at:
Arch Dermatol 2007;143:1131-1136. Available at: https://www.ncbi.nlm.nih.gov/pubmed/17903153.
http://www.ncbi.nlm.nih.gov/pubmed/17875873.
152. Kappelin J, Nielsen K, Nilsson F, et al. Surgical treatment of
144. Wetzig T, Woitek M, Eichhorn K, et al. Surgical excision of basal basal cell carcinoma: a case series on factors influencing the risk of an
cell carcinoma with complete margin control: outcome at 5-year follow- incomplete primary excision. J Eur Acad Dermatol Venereol
up. Dermatology 2010;220:363-369. Available at: 2020;34:2518-2525. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/20484877. https://www.ncbi.nlm.nih.gov/pubmed/32124503.

145. Schell AE, Russell MA, Park SS. Suggested excisional margins 153. Dieu T, Macleod AM. Incomplete excision of basal cell
for cutaneous malignant lesions based on Mohs micrographic surgery. carcinomas: a retrospective audit. ANZ J Surg 2002;72:219-221.
JAMA Facial Plast Surg 2013;15:337-343. Available at: Available at: https://www.ncbi.nlm.nih.gov/pubmed/12071456.
https://www.ncbi.nlm.nih.gov/pubmed/23744451.
154. Ramdas K, van Lee C, Beck S, et al. Differences in Rate of
146. Quazi SJ, Aslam N, Saleem H, et al. Surgical Margin of Excision Complete Excision of Basal Cell Carcinoma by Dermatologists, Plastic
in Basal Cell Carcinoma: A Systematic Review of Literature. Cureus Surgeons and General Practitioners: A Large Cross-Sectional Study.
2020;12:e9211. Available at: Dermatology 2018;234:86-91. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/32821563. https://www.ncbi.nlm.nih.gov/pubmed/30086541.
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-22
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
155. Sexton M, Jones DB, Maloney ME. Histologic pattern analysis of 163. Wennberg AM, Larko O, Stenquist B. Five-year results of Mohs'
basal cell carcinoma. Study of a series of 1039 consecutive micrographic surgery for aggressive facial basal cell carcinoma in
neoplasms. J Am Acad Dermatol 1990;23:1118-1126. Available at: Sweden. Acta Derm Venereol 1999;79:370-372. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/2273112. http://www.ncbi.nlm.nih.gov/pubmed/10494714.

156. Sherry KR, Reid LA, Wilmshurst AD. A five year review of basal 164. Veronese F, Farinelli P, Zavattaro E, et al. Basal cell carcinoma
cell carcinoma excisions. J Plast Reconstr Aesthet Surg of the head region: therapeutical results of 350 lesions treated with
2010;63:1485-1489. Available at: Mohs micrographic surgery. J Eur Acad Dermatol Venereol
https://www.ncbi.nlm.nih.gov/pubmed/19837017. 2012;26:838-843. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/21707774.
157. Griffiths RW, Suvarna SK, Stone J. Basal cell carcinoma
histological clearance margins: an analysis of 1539 conventionally 165. Litwin AS, Rytina E, Ha T, et al. Management of periocular basal
excised tumours. Wider still and deeper? J Plast Reconstr Aesthet cell carcinoma by Mohs micrographic surgery. J Dermatolog Treat
Surg 2007;60:41-47. Available at: 2013;24:232-234. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/17126265. https://www.ncbi.nlm.nih.gov/pubmed/22551161.

158. Masud D, Moustaki M, Staruch R, Dheansa B. Basal cell 166. Sin CW, Barua A, Cook A. Recurrence rates of periocular basal
carcinomata: Risk factors for incomplete excision and results of re- cell carcinoma following Mohs micrographic surgery: a retrospective
excision. J Plast Reconstr Aesthet Surg 2016;69:652-656. Available study. Int J Dermatol 2016;55:1044-1047. Available at:
at: http://www.ncbi.nlm.nih.gov/pubmed/26948998. https://www.ncbi.nlm.nih.gov/pubmed/27152747.

159. Malik V, Goh KS, Leong S, et al. Risk and outcome analysis of 167. Leibovitch I, Huilgol SC, Selva D, et al. Basal cell carcinoma
1832 consecutively excised basal cell carcinomas in a tertiary referral treated with Mohs surgery in Australia II. Outcome at 5-year follow-up.
plastic surgery unit. J Plast Reconstr Aesthet Surg 2010;63:2057- J Am Acad Dermatol 2005;53:452-457. Available at:
2063. Available at: https://www.ncbi.nlm.nih.gov/pubmed/20226750. http://www.ncbi.nlm.nih.gov/pubmed/16112352.

160. Wolf DJ, Zitelli JA. Surgical margins for basal cell carcinoma. 168. Malhotra R, Huilgol SC, Huynh NT, Selva D. The Australian Mohs
Arch Dermatol 1987;123:340-344. Available at: database, part II: periocular basal cell carcinoma outcome at 5-year
http://www.ncbi.nlm.nih.gov/pubmed/3813602. follow-up. Ophthalmology 2004;111:631-636. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/15051193.
161. Weesie F, Naus NC, Vasilic D, et al. Recurrence of periocular
basal cell carcinoma and squamous cell carcinoma after Mohs 169. Mosterd K, Krekels GA, Nieman FH, et al. Surgical excision
micrographic surgery: a retrospective cohort study. Br J Dermatol versus Mohs' micrographic surgery for primary and recurrent basal-cell
2019;180:1176-1182. Available at: carcinoma of the face: a prospective randomised controlled trial with
https://www.ncbi.nlm.nih.gov/pubmed/30536656. 5-years' follow-up. Lancet Oncol 2008;9:1149-1156. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/19010733.
162. Drucker AM, Adam GP, Rofeberg V, et al. Treatments of Primary
Basal Cell Carcinoma of the Skin: A Systematic Review and Network 170. van Loo E, Mosterd K, Krekels GA, et al. Surgical excision versus
Meta-analysis. Ann Intern Med 2018;169:456-466. Available at: Mohs' micrographic surgery for basal cell carcinoma of the face: A
https://www.ncbi.nlm.nih.gov/pubmed/30242379. randomised clinical trial with 10 year follow-up. Eur J Cancer
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-23
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
2014;50:3011-3020. Available at: neck. Laryngoscope 2009;119:1994-1999. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/25262378. http://www.ncbi.nlm.nih.gov/pubmed/19688856.

171. Smeets NW, Krekels GA, Ostertag JU, et al. Surgical excision vs 178. Mendenhall WM, Ferlito A, Takes RP, et al. Cutaneous head and
Mohs' micrographic surgery for basal-cell carcinoma of the face: neck basal and squamous cell carcinomas with perineural invasion.
randomised controlled trial. Lancet 2004;364:1766-1772. Available at: Oral Oncol 2012;48:918-922. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/15541449. http://www.ncbi.nlm.nih.gov/pubmed/22425152.

172. Muller FM, Dawe RS, Moseley H, Fleming CJ. Randomized 179. Han A, Ratner D. What is the role of adjuvant radiotherapy in the
comparison of Mohs micrographic surgery and surgical excision for treatment of cutaneous squamous cell carcinoma with perineural
small nodular basal cell carcinoma: tissue-sparing outcome. Dermatol invasion? Cancer 2007;109:1053-1059. Available at:
Surg 2009;35:1349-1354. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17279578.
https://www.ncbi.nlm.nih.gov/pubmed/19500127.
180. Wilder RB, Kittelson JM, Shimm DS. Basal cell carcinoma treated
173. Gniadecki R, Glud M, Mortensen K, et al. Favourable results of with radiation therapy. Cancer 1991;68:2134-2137. Available at:
Mohs micrographic surgery for basal cell carcinoma. Dan Med J http://www.ncbi.nlm.nih.gov/pubmed/1913451.
2015;62:A5171. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/26621396. 181. Wilder RB, Shimm DS, Kittelson JM, et al. Recurrent basal cell
carcinoma treated with radiation therapy. Arch Dermatol
174. Flohil SC, van Dorst AM, Nijsten T, et al. Mohs micrographic 1991;127:1668-1672. Available at:
surgery for basal cell carcinomas: appropriateness of 'Rotterdam' http://www.ncbi.nlm.nih.gov/pubmed/1952970.
criteria and predictive factors for three or more stages. J Eur Acad
Dermatol Venereol 2013;27:1228-1235. Available at: 182. Childers BJ, Goldwyn RM, Ramos D, et al. Long-term results of
http://www.ncbi.nlm.nih.gov/pubmed/23039378. irradiation for basal cell carcinoma of the skin of the nose. Plast
Reconstr Surg 1994;93:1169-1173. Available at:
175. Takata Pontes L, Fantelli Stelini R, Cintra ML, et al. The http://www.ncbi.nlm.nih.gov/pubmed/8171136.
importance of superficial basal cell carcinoma in a retrospective study
of 139 patients who underwent Mohs micrographic surgery in a 183. Hernandez-Machin B, Borrego L, Gil-Garcia M, Hernandez BH.
Brazilian university hospital. Clinics (Sao Paulo) 2015;70:721-725. Office-based radiation therapy for cutaneous carcinoma: evaluation of
Available at: https://www.ncbi.nlm.nih.gov/pubmed/26602517. 710 treatments. Int J Dermatol 2007;46:453-459. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/17472670.
176. Morris DS, Elzaridi E, Clarke L, et al. Periocular basal cell
carcinoma: 5-year outcome following Slow Mohs surgery with formalin- 184. Silverman MK, Kopf AW, Gladstein AH, et al. Recurrence rates of
fixed paraffin-embedded sections and delayed closure. Br J treated basal cell carcinomas. Part 4: X-ray therapy. J Dermatol Surg
Ophthalmol 2009;93:474-476. Available at: Oncol 1992;18:549-554. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/19060015. http://www.ncbi.nlm.nih.gov/pubmed/1624628.

177. Mendenhall WM, Amdur RJ, Hinerman RW, et al. Radiotherapy 185. Zagrodnik B, Kempf W, Seifert B, et al. Superficial radiotherapy
for cutaneous squamous and basal cell carcinomas of the head and for patients with basal cell carcinoma: recurrence rates, histologic

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-24
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
subtypes, and expression of p53 and Bcl-2. Cancer 2003;98:2708- 193. Cipriani C, Desantis M, Dahlhoff G, et al. Personalized irradiation
2714. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14669293. therapy for NMSC by rhenium-188 skin cancer therapy: a long-term
retrospective study. J Dermatolog Treat 2020:1-7. Available at:
186. Cognetta AB, Howard BM, Heaton HP, et al. Superficial x-ray in https://www.ncbi.nlm.nih.gov/pubmed/32648530.
the treatment of basal and squamous cell carcinomas: a viable option
in select patients. J Am Acad Dermatol 2012;67:1235-1241. Available 194. Sedda AF, Rossi G, Cipriani C, et al. Dermatological high-dose-
at: http://www.ncbi.nlm.nih.gov/pubmed/22818756. rate brachytherapy for the treatment of basal and squamous cell
carcinoma. Clin Exp Dermatol 2008;33:745-749. Available at:
187. Avril MF, Auperin A, Margulis A, et al. Basal cell carcinoma of the http://www.ncbi.nlm.nih.gov/pubmed/18681873.
face: surgery or radiotherapy? Results of a randomized study. Br J
Cancer 1997;76:100-106. Available at: 195. Guibert M, David I, Vergez S, et al. Brachytherapy in lip
http://www.ncbi.nlm.nih.gov/pubmed/9218740. carcinoma: long-term results. Int J Radiat Oncol Biol Phys
2011;81:e839-843. Available at:
188. Petit JY, Avril MF, Margulis A, et al. Evaluation of cosmetic https://www.ncbi.nlm.nih.gov/pubmed/21163589.
results of a randomized trial comparing surgery and radiotherapy in
the treatment of basal cell carcinoma of the face. Plast Reconstr Surg 196. Ballester-Sanchez R, Pons-Llanas O, Candela-Juan C, et al. Two
2000;105:2544-2551. Available at: years results of electronic brachytherapy for basal cell carcinoma. J
http://www.ncbi.nlm.nih.gov/pubmed/10845311. Contemp Brachytherapy 2017;9:251-255. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/28725249.
189. Hall VL, Leppard BJ, McGill J, et al. Treatment of basal-cell
carcinoma: comparison of radiotherapy and cryotherapy. Clin Radiol 197. Bhatnagar A, Loper A. The initial experience of electronic
1986;37:33-34. Available at: brachytherapy for the treatment of non-melanoma skin cancer. Radiat
http://www.ncbi.nlm.nih.gov/pubmed/3514075. Oncol 2010;5:87. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/20875139.
190. Garcia-Martin E, Gil-Arribas LM, Idoipe M, et al. Comparison of
imiquimod 5% cream versus radiotherapy as treatment for eyelid basal 198. Braathen LR, Szeimies RM, Basset-Seguin N, et al. Guidelines
cell carcinoma. Br J Ophthalmol 2011;95:1393-1396. Available at: on the use of photodynamic therapy for nonmelanoma skin cancer: an
https://www.ncbi.nlm.nih.gov/pubmed/21242584. international consensus. International Society for Photodynamic
Therapy in Dermatology, 2005. J Am Acad Dermatol 2007;56:125-143.
191. Zaorsky NG, Lee CT, Zhang E, et al. Hypofractionated radiation Available at: http://www.ncbi.nlm.nih.gov/pubmed/17190630.
therapy for basal and squamous cell skin cancer: A meta-analysis.
Radiother Oncol 2017;125:13-20. Available at: 199. Jansen MHE, Mosterd K, Arits A, et al. Five-Year Results of a
https://www.ncbi.nlm.nih.gov/pubmed/28843727. Randomized Controlled Trial Comparing Effectiveness of
Photodynamic Therapy, Topical Imiquimod, and Topical 5-Fluorouracil
192. Ashby MA, Pacella JA, de Groot R, Ainslie J. Use of a radon in Patients with Superficial Basal Cell Carcinoma. J Invest Dermatol
mould technique for skin cancer: results from the Peter MacCallum 2018;138:527-533. Available at:
Cancer Institute (1975-1984). Br J Radiol 1989;62:608-612. Available https://www.ncbi.nlm.nih.gov/pubmed/29045820.
at: https://www.ncbi.nlm.nih.gov/pubmed/2758248.
200. Drew BA, Karia PS, Mora AN, et al. Treatment Patterns,
Outcomes, and Patient Satisfaction of Primary Epidermally Limited
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-25
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Nonmelanoma Skin Cancer. Dermatol Surg 2017;43:1423-1430. cream: conclusion of a 5-year long-term follow-up study in Europe. Eur
Available at: https://www.ncbi.nlm.nih.gov/pubmed/28661992. J Dermatol 2008;18:677-682. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/18955210.
201. Peris K, Campione E, Micantonio T, et al. Imiquimod treatment of
superficial and nodular basal cell carcinoma: 12-week open-label trial. 208. McKay KM, Sambrano BL, Fox PS, et al. Thickness of superficial
Dermatol Surg 2005;31:318-323. Available at: basal cell carcinoma (sBCC) predicts imiquimod efficacy: a proposal
https://www.ncbi.nlm.nih.gov/pubmed/15841634. for a thickness-based definition of sBCC. Br J Dermatol 2013;169:549-
554. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23627639.
202. Eigentler TK, Kamin A, Weide BM, et al. A phase III, randomized,
open label study to evaluate the safety and efficacy of imiquimod 5% 209. Bath-Hextall F, Ozolins M, Armstrong SJ, et al. Surgical excision
cream applied thrice weekly for 8 and 12 weeks in the treatment of versus imiquimod 5% cream for nodular and superficial basal-cell
low-risk nodular basal cell carcinoma. J Am Acad Dermatol carcinoma (SINS): a multicentre, non-inferiority, randomised controlled
2007;57:616-621. Available at: trial. Lancet Oncol 2014;15:96-105. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/17610993. http://www.ncbi.nlm.nih.gov/pubmed/24332516.

203. Geisse J, Caro I, Lindholm J, et al. Imiquimod 5% cream for the 210. Williams HC, Bath-Hextall F, Ozolins M, et al. Surgery Versus 5%
treatment of superficial basal cell carcinoma: results from two phase Imiquimod for Nodular and Superficial Basal Cell Carcinoma: 5-Year
III, randomized, vehicle-controlled studies. J Am Acad Dermatol Results of the SINS Randomized Controlled Trial. J Invest Dermatol
2004;50:722-733. Available at: 2017;137:614-619. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/15097956. https://www.ncbi.nlm.nih.gov/pubmed/27932240.

204. Schulze HJ, Cribier B, Requena L, et al. Imiquimod 5% cream for 211. Metterle L, Nelson C, Patel N. Intralesional 5-fluorouracil (FU) as
the treatment of superficial basal cell carcinoma: results from a a treatment for nonmelanoma skin cancer (NMSC): A review. J Am
randomized vehicle-controlled phase III study in Europe. Br J Acad Dermatol 2016;74:552-557. Available at:
Dermatol 2005;152:939-947. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26577512.
http://www.ncbi.nlm.nih.gov/pubmed/15888150.
212. Neale H, Michelon M, Jacob S, et al. Topical 5% 5-fluorouracil
205. Quirk C, Gebauer K, De'Ambrosis B, et al. Sustained clearance versus procedural modalities for squamous cell carcinoma in situ and
of superficial basal cell carcinomas treated with imiquimod cream 5%: superficial basal cell carcinoma: A retrospective cohort analysis. J Am
results of a prospective 5-year study. Cutis 2010;85:318-324. Acad Dermatol 2021. Available at:
Available at: http://www.ncbi.nlm.nih.gov/pubmed/20666194. https://www.ncbi.nlm.nih.gov/pubmed/34478783.

206. Marks R, Gebauer K, Shumack S, et al. Imiquimod 5% cream in 213. Arits AH, Mosterd K, Essers BA, et al. Photodynamic therapy
the treatment of superficial basal cell carcinoma: results of a versus topical imiquimod versus topical fluorouracil for treatment of
multicenter 6-week dose-response trial. J Am Acad Dermatol superficial basal-cell carcinoma: a single blind, non-inferiority,
2001;44:807-813. Available at: randomised controlled trial. Lancet Oncol 2013;14:647-654. Available
https://www.ncbi.nlm.nih.gov/pubmed/11312429. at: http://www.ncbi.nlm.nih.gov/pubmed/23683751.

207. Gollnick H, Barona CG, Frank RG, et al. Recurrence rate of 214. Roozeboom MH, Arits A, Mosterd K, et al. Three-Year Follow-Up
superficial basal cell carcinoma following treatment with imiquimod 5% Results of Photodynamic Therapy vs. Imiquimod vs. Fluorouracil for
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-26
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Treatment of Superficial Basal Cell Carcinoma: A Single-Blind, Dermatol 2007;157:401-403. Available at:
Noninferiority, Randomized Controlled Trial. J Invest Dermatol http://www.ncbi.nlm.nih.gov/pubmed/17573890.
2016;136:1568-1574. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/27113429. 222. Szeimies RM, Ibbotson S, Murrell DF, et al. A clinical study
comparing methyl aminolevulinate photodynamic therapy and surgery
215. Gross K, Kircik L, Kricorian G. 5% 5-Fluorouracil cream for the in small superficial basal cell carcinoma (8-20 mm), with a 12-month
treatment of small superficial Basal cell carcinoma: efficacy, follow-up. J Eur Acad Dermatol Venereol 2008;22:1302-1311.
tolerability, cosmetic outcome, and patient satisfaction. Dermatol Surg Available at: http://www.ncbi.nlm.nih.gov/pubmed/18624836.
2007;33:433-439; discussion 440. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/17430377. 223. Roozeboom MH, Aardoom MA, Nelemans PJ, et al. Fractionated
5-aminolevulinic acid photodynamic therapy after partial debulking
216. Reymann F. Treatment of basal cell carcinoma of the skin with 5- versus surgical excision for nodular basal cell carcinoma: a
fluorouracil ointment. A 10-year follow-up study. Dermatologica randomized controlled trial with at least 5-year follow-up. J Am Acad
1979;158:368-372. Available at: Dermatol 2013;69:280-287. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/437226. http://www.ncbi.nlm.nih.gov/pubmed/23566914.

217. Love WE, Bernhard JD, Bordeaux JS. Topical imiquimod or 224. Cosgarea R, Susan M, Crisan M, Senila S. Photodynamic
fluorouracil therapy for basal and squamous cell carcinoma: a therapy using topical 5-aminolaevulinic acid vs. surgery for basal cell
systematic review. Arch Dermatol 2009;145:1431-1438. Available at: carcinoma. J Eur Acad Dermatol Venereol 2013;27:980-984. Available
https://www.ncbi.nlm.nih.gov/pubmed/20026854. at: http://www.ncbi.nlm.nih.gov/pubmed/22738399.

218. Kuijpers DI, Thissen MR, Thissen CA, Neumann MH. Similar 225. Wang H, Xu Y, Shi J, et al. Photodynamic therapy in the
effectiveness of methyl aminolevulinate and 5-aminolevulinate in treatment of basal cell carcinoma: a systematic review and meta-
topical photodynamic therapy for nodular basal cell carcinoma. J analysis. Photodermatol Photoimmunol Photomed 2015;31:44-53.
Drugs Dermatol 2006;5:642-645. Available at: Available at: http://www.ncbi.nlm.nih.gov/pubmed/25377432.
http://www.ncbi.nlm.nih.gov/pubmed/16865869.
226. Rhodes LE, de Rie M, Enstrom Y, et al. Photodynamic therapy
219. Savoia P, Deboli T, Previgliano A, Broganelli P. Usefulness of using topical methyl aminolevulinate vs surgery for nodular basal cell
photodynamic therapy as a possible therapeutic alternative in the carcinoma: results of a multicenter randomized prospective trial. Arch
treatment of basal cell carcinoma. Int J Mol Sci 2015;16:23300-23317. Dermatol 2004;140:17-23. Available at:
Available at: http://www.ncbi.nlm.nih.gov/pubmed/26426005. http://www.ncbi.nlm.nih.gov/pubmed/14732655.

220. Oseroff AR, Blumenson LR, Wilson BD, et al. A dose ranging 227. Collier NJ, Haylett AK, Wong TH, et al. Conventional and
study of photodynamic therapy with porfimer sodium (Photofrin) for combination topical photodynamic therapy for basal cell carcinoma:
treatment of basal cell carcinoma. Lasers Surg Med 2006;38:417-426. systematic review and meta-analysis. Br J Dermatol 2018;179:1277-
Available at: https://www.ncbi.nlm.nih.gov/pubmed/16788928. 1296. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29889302.

221. Berroeta L, Clark C, Dawe RS, et al. A randomized study of 228. Zou Y, Zhao Y, Yu J, et al. Photodynamic therapy versus surgical
minimal curettage followed by topical photodynamic therapy compared excision to basal cell carcinoma: meta-analysis. J Cosmet Dermatol
with surgical excision for low-risk nodular basal cell carcinoma. Br J
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-27
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
2016;15:374-382. Available at: 236. Sotiriou E, Apalla Z, Maliamani F, et al. Intraindividual, right-left
https://www.ncbi.nlm.nih.gov/pubmed/27363535. comparison of topical 5-aminolevulinic acid photodynamic therapy vs.
5% imiquimod cream for actinic keratoses on the upper extremities. J
229. Horn M, Wolf P, Wulf HC, et al. Topical methyl aminolaevulinate Eur Acad Dermatol Venereol 2009;23:1061-1065. Available at:
photodynamic therapy in patients with basal cell carcinoma prone to http://www.ncbi.nlm.nih.gov/pubmed/19470041.
complications and poor cosmetic outcome with conventional
treatment. Br J Dermatol 2003;149:1242-1249. Available at: 237. Morton CA, McKenna KE, Rhodes LE. Guidelines for topical
http://www.ncbi.nlm.nih.gov/pubmed/14674903. photodynamic therapy: update. Br J Dermatol 2008;159:1245-1266.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/18945319.
230. Christensen E, Mork C, Skogvoll E. High and sustained efficacy
after two sessions of topical 5-aminolaevulinic acid photodynamic 238. Kokoszka A, Scheinfeld N. Evidence-based review of the use of
therapy for basal cell carcinoma: a prospective, clinical and cryosurgery in treatment of basal cell carcinoma. Dermatol Surg
histological 10-year follow-up study. Br J Dermatol 2012;166:1342- 2003;29:566-571. Available at:
1348. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22309486. http://www.ncbi.nlm.nih.gov/pubmed/12786697.

231. Zeitouni NC, Shieh S, Oseroff AR. Laser and photodynamic 239. Kuflik EG, Gage AA. The five-year cure rate achieved by
therapy in the management of cutaneous malignancies. Clin Dermatol cryosurgery for skin cancer. J Am Acad Dermatol 1991;24:1002-1004.
2001;19:328-338. Available at: Available at: http://www.ncbi.nlm.nih.gov/pubmed/1820761.
http://www.ncbi.nlm.nih.gov/pubmed/11479045.
240. Mallon E, Dawber R. Cryosurgery in the treatment of basal cell
232. Osiecka B, Jurczyszyn K, Ziolkowski P. The application of carcinoma. Assessment of one and two freeze-thaw cycle schedules.
Levulan-based photodynamic therapy with imiquimod in the treatment Dermatol Surg 1996;22:854-858. Available at:
of recurrent basal cell carcinoma. Med Sci Monit 2012;18:PI5-9. http://www.ncbi.nlm.nih.gov/pubmed/9246168.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/22293891.
241. Wang I, Bendsoe N, Klinteberg CA, et al. Photodynamic therapy
233. Mosterd K, Thissen MR, Nelemans P, et al. Fractionated 5- vs. cryosurgery of basal cell carcinomas: results of a phase III clinical
aminolaevulinic acid-photodynamic therapy vs. surgical excision in the trial. Br J Dermatol 2001;144:832-840. Available at:
treatment of nodular basal cell carcinoma: results of a randomized http://www.ncbi.nlm.nih.gov/pubmed/11298545.
controlled trial. Br J Dermatol 2008;159:864-870. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/18717680. 242. Basset-Seguin N, Ibbotson SH, Emtestam L, et al. Topical methyl
aminolaevulinate photodynamic therapy versus cryotherapy for
234. Fantini F, Greco A, Del Giovane C, et al. Photodynamic therapy superficial basal cell carcinoma: a 5 year randomized trial. Eur J
for basal cell carcinoma: clinical and pathological determinants of Dermatol 2008;18:547-553. Available at:
response. J Eur Acad Dermatol Venereol 2011;25:896-901. Available http://www.ncbi.nlm.nih.gov/pubmed/18693158.
at: http://www.ncbi.nlm.nih.gov/pubmed/21054566.
243. Thissen MR, Nieman FH, Ideler AH, et al. Cosmetic results of
235. Vinciullo C, Elliott T, Francis D, et al. Photodynamic therapy with cryosurgery versus surgical excision for primary uncomplicated basal
topical methyl aminolaevulinate for 'difficult-to-treat' basal cell cell carcinomas of the head and neck. Dermatol Surg 2000;26:759-
carcinoma. Br J Dermatol 2005;152:765-772. Available at: 764. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10940063.
http://www.ncbi.nlm.nih.gov/pubmed/15840111.
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-28
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
244. Roozeboom MH, Arits AH, Nelemans PJ, Kelleners-Smeets NW. Squamous Cell Carcinoma, and Basal Cell Carcinoma: A Systematic
Overall treatment success after treatment of primary superficial basal Review. JAMA Dermatol 2020;156:1117-1124. Available at:
cell carcinoma: a systematic review and meta-analysis of randomized https://www.ncbi.nlm.nih.gov/pubmed/32639538.
and nonrandomized trials. Br J Dermatol 2012;167:733-756. Available
at: http://www.ncbi.nlm.nih.gov/pubmed/22612571. 252. Tang JY, Chiou AS, Mackay-Wiggan JM, et al. Tazarotene:
randomized, double-blind, vehicle-controlled, and open-label
245. Roozeboom MH, Nelemans PJ, Mosterd K, et al. Photodynamic concurrent trials for basal cell carcinoma prevention and therapy in
therapy vs. topical imiquimod for treatment of superficial basal cell patients with basal cell nevus syndrome. Cancer Prev Res (Phila)
carcinoma: a subgroup analysis within a noninferiority randomized 2014;7:292-299. Available at:
controlled trial. Br J Dermatol 2015;172:739-745. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24441673.
http://www.ncbi.nlm.nih.gov/pubmed/25066012.
253. Prescribing information: Vismodegib capsule for oral use. 2019.
246. Chen AC, Martin AJ, Choy B, et al. A Phase 3 Randomized Trial Available at:
of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203388s0
2015;373:1618-1626. Available at: 14lbl.pdf. Accessed June 26, 2019.
http://www.ncbi.nlm.nih.gov/pubmed/26488693.
254. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of
247. Chen AC, Martin AJ, Dalziell RA, et al. A Phase 2 Randomised vismodegib in advanced basal-cell carcinoma. N Engl J Med
Controlled Trial of Nicotinamide for Skin Cancer Chemoprevention in 2012;366:2171-2179. Available at:
Renal Transplant Recipients. Br J Dermatol 2016. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22670903.
https://pubmed.ncbi.nlm.nih.gov/27061568/.
255. Sekulic A, Migden MR, Basset-Seguin N, et al. Long-term safety
248. Surjana D, Halliday GM, Martin AJ, et al. Oral nicotinamide and efficacy of vismodegib in patients with advanced basal cell
reduces actinic keratoses in phase II double-blinded randomized carcinoma: final update of the pivotal ERIVANCE BCC study. BMC
controlled trials. J Invest Dermatol 2012;132:1497-1500. Available at: Cancer 2017;17:332. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/22297641. https://www.ncbi.nlm.nih.gov/pubmed/28511673.

249. Elmets CA, Viner JL, Pentland AP, et al. Chemoprevention of 256. Sekulic A, Migden MR, Lewis K, et al. Pivotal ERIVANCE basal
nonmelanoma skin cancer with celecoxib: a randomized, double-blind, cell carcinoma (BCC) study: 12-month update of efficacy and safety of
placebo-controlled trial. J Natl Cancer Inst 2010;102:1835-1844. vismodegib in advanced BCC. J Am Acad Dermatol 2015;72:1021-
Available at: https://www.ncbi.nlm.nih.gov/pubmed/21115882. 1026.e1028. Available at: https://pubmed.ncbi.nlm.nih.gov/25981002/.

250. Kadakia KC, Barton DL, Loprinzi CL, et al. Randomized 257. Dreno B, Basset-Seguin N, Caro I, et al. Clinical benefit
controlled trial of acitretin versus placebo in patients at high-risk for assessment of vismodegib therapy in patients with advanced basal
basal cell or squamous cell carcinoma of the skin (North Central cell carcinoma. Oncologist 2014;19:790-796. Available at:
Cancer Treatment Group Study 969251). Cancer 2012;118:2128- http://www.ncbi.nlm.nih.gov/pubmed/25001266.
2137. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21882176.
258. Chang AL, Solomon JA, Hainsworth JD, et al. Expanded access
251. Schauder DM, Kim J, Nijhawan RI. Evaluation of the Use of study of patients with advanced basal cell carcinoma treated with the
Capecitabine for the Treatment and Prevention of Actinic Keratoses, Hedgehog pathway inhibitor, vismodegib. J Am Acad Dermatol
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-29
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
2014;70:60-69. Available at: Dermatol Ther (Heidelb) 2021. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/24189279. https://www.ncbi.nlm.nih.gov/pubmed/34669179.

259. Basset-Seguin N, Hauschild A, Grob JJ, et al. Vismodegib in 266. Lear JT, Migden MR, Lewis KD, et al. Long-term efficacy and
patients with advanced basal cell carcinoma (STEVIE): a pre-planned safety of sonidegib in patients with locally advanced and metastatic
interim analysis of an international, open-label trial. Lancet Oncol basal cell carcinoma: 30-month analysis of the randomized phase 2
2015;16:729-736. Available at: BOLT study. J Eur Acad Dermatol Venereol 2018;32:372-381.
http://www.ncbi.nlm.nih.gov/pubmed/25981813. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28846163.

260. Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al. Inhibiting the 267. Dummer R, Guminksi A, Gutzmer R, et al. Long-term efficacy and
hedgehog pathway in patients with the basal-cell nevus syndrome. N safety of sonidegib in patients with advanced basal cell carcinoma: 42-
Engl J Med 2012;366:2180-2188. Available at: month analysis of the phase II randomized, double-blind BOLT study.
http://www.ncbi.nlm.nih.gov/pubmed/22670904. Br J Dermatol 2020;182:1369-1378. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/31545507.
261. Tang JY, Ally MS, Chanana AM, et al. Inhibition of the hedgehog
pathway in patients with basal-cell nevus syndrome: final results from 268. Dummer R, Lear JT, Guminski A, et al. Efficacy of sonidegib in
the multicentre, randomised, double-blind, placebo-controlled, phase 2 histologic subtypes of advanced basal cell carcinoma: Results from
trial. Lancet Oncol 2016;17:1720-1731. Available at: the final analysis of the randomized phase 2 Basal Cell Carcinoma
https://www.ncbi.nlm.nih.gov/pubmed/27838224. Outcomes With LDE225 Treatment (BOLT) trial at 42 months. J Am
Acad Dermatol 2021;84:1162-1164. Available at:
262. Ally MS, Tang JY, Joseph T, et al. The use of vismodegib to https://www.ncbi.nlm.nih.gov/pubmed/33358380.
shrink keratocystic odontogenic tumors in patients with basal cell
nevus syndrome. JAMA Dermatol 2014;150:542-545. Available at: 269. Danial C, Sarin KY, Oro AE, Chang AL. An investigator-initiated
https://www.ncbi.nlm.nih.gov/pubmed/24623282. open-label trial of sonidegib in advanced basal cell carcinoma patients
resistant to vismodegib. Clin Cancer Res 2016;22:1325-1329.
263. Prescribing information: Sonidegib capsules, for oral use. 2019. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26546616.
Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/205266s0 270. Ally MS, Aasi S, Wysong A, et al. An investigator-initiated open-
06lbl.pdf. Accessed june 26, 2019. label clinical trial of vismodegib as a neoadjuvant to surgery for high-
risk basal cell carcinoma. J Am Acad Dermatol 2014;71:904-911.e901.
264. Migden MR, Guminski A, Gutzmer R, et al. Treatment with two Available at: http://www.ncbi.nlm.nih.gov/pubmed/24929884.
different doses of sonidegib in patients with locally advanced or
metastatic basal cell carcinoma (BOLT): a multicentre, randomised, 271. Sofen H, Gross KG, Goldberg LH, et al. A phase II, multicenter,
double-blind phase 2 trial. Lancet Oncol 2015;16:716-728. Available open-label, 3-cohort trial evaluating the efficacy and safety of
at: http://www.ncbi.nlm.nih.gov/pubmed/25981810. vismodegib in operable basal cell carcinoma. J Am Acad Dermatol
2015;73:99-105.e101. Available at:
265. Lewis K, Dummer R, Farberg AS, et al. Effects of Sonidegib http://www.ncbi.nlm.nih.gov/pubmed/25913533.
Following Dose Reduction and Treatment Interruption in Patients with
Advanced Basal Cell Carcinoma During 42-Month BOLT Trial. 272. Tauber G, Pavlovsky L, Fenig E, Hodak E. Vismodegib for
radiation-induced multiple basal cell carcinomas (BCCs) of the scalp. J
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-30
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
Am Acad Dermatol 2015;73:799-801. Available at: 2021;22:848-857. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/26320385. https://www.ncbi.nlm.nih.gov/pubmed/34000246.

273. Bertrand N, Guerreschi P, Basset-Seguin N, et al. Vismodegib in 280. Carneiro BA, Watkin WG, Mehta UK, Brockstein BE. Metastatic
neoadjuvant treatment of locally advanced basal cell carcinoma: First basal cell carcinoma: complete response to chemotherapy and
results of a multicenter, open-label, phase 2 trial (VISMONEO study): associated pure red cell aplasia. Cancer Invest 2006;24:396-400.
Neoadjuvant Vismodegib in Locally Advanced Basal Cell Carcinoma. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16777692.
EClinicalMedicine 2021;35:100844. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/33997740. 281. Jefford M, Kiffer JD, Somers G, et al. Metastatic basal cell
carcinoma: rapid symptomatic response to cisplatin and paclitaxel.
274. Dreno B, Kunstfeld R, Hauschild A, et al. Two intermittent ANZ J Surg 2004;74:704-705. Available at:
vismodegib dosing regimens in patients with multiple basal-cell http://www.ncbi.nlm.nih.gov/pubmed/15315581.
carcinomas (MIKIE): a randomised, regimen-controlled, double-blind,
phase 2 trial. Lancet Oncol 2017;18:404-412. Available at: 282. Ganti AK, Kessinger A. Systemic therapy for disseminated basal
https://www.ncbi.nlm.nih.gov/pubmed/28188086. cell carcinoma: an uncommon manifestation of a common cancer.
Cancer Treat Rev 2011;37:440-443. Available at:
275. Scalvenzi M, Cappello M, Costa C, et al. Low-Dose Vismodegib http://www.ncbi.nlm.nih.gov/pubmed/21216106.
as Maintenance Therapy After Locally Advanced Basal Cell
Carcinoma Complete Remission: High Efficacy with Minimal Toxicity. 283. Wysong A, Aasi SZ, Tang JY. Update on metastatic basal cell
Dermatol Ther (Heidelb) 2020;10:465-468. Available at: carcinoma: a summary of published cases from 1981 through 2011.
https://www.ncbi.nlm.nih.gov/pubmed/32240528. JAMA Dermatol 2013;149:615-616. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/23677097.
276. Jimeno A, Weiss GJ, Miller WH, Jr., et al. Phase I study of the
Hedgehog pathway inhibitor IPI-926 in adult patients with solid tumors. 284. Pfeiffer P, Hansen O, Rose C. Systemic cytotoxic therapy of
Clin Cancer Res 2013;19:2766-2774. Available at: basal cell carcinoma. A review of the literature. Eur J Cancer
http://www.ncbi.nlm.nih.gov/pubmed/23575478. 1990;26:73-77. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/2138485.
277. Kim DJ, Kim J, Spaunhurst K, et al. Open-label, exploratory
phase II trial of oral itraconazole for the treatment of basal cell 285. Moeholt K, Aagaard H, Pfeiffer P, Hansen O. Platinum-based
carcinoma. J Clin Oncol 2014;32:745-751. Available at: cytotoxic therapy in basal cell carcinoma--a review of the literature.
http://www.ncbi.nlm.nih.gov/pubmed/24493717. Acta Oncol 1996;35:677-682. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/8938213.
278. Prescribing information: cemiplimab-rwlc injection, for
intravenous use. 2019. Available at: 286. Guthrie TH, Jr., Porubsky ES, Luxenberg MN, et al. Cisplatin-
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761097s0 based chemotherapy in advanced basal and squamous cell
02lbl.pdf. Accessed June 26, 2019. carcinomas of the skin: results in 28 patients including 13 patients
receiving multimodality therapy. J Clin Oncol 1990;8:342-346.
279. Stratigos AJ, Sekulic A, Peris K, et al. Cemiplimab in locally Available at: http://www.ncbi.nlm.nih.gov/pubmed/2405109.
advanced basal cell carcinoma after hedgehog inhibitor therapy: an
open-label, multi-centre, single-arm, phase 2 trial. Lancet Oncol
Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-31
Printed by LEONARDO MACEDO on 6/30/2023 7:39:40 PM. For personal use only. Not approved for distribution. Copyright © 2023 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2023


Basal Cell Skin Cancer
287. Basset-Seguin N, Hauschild A, Kunstfeld R, et al. Vismodegib in 294. Ramachandran S, Rajaratnam R, Smith AG, et al. Patients with
patients with advanced basal cell carcinoma: Primary analysis of both basal and squamous cell carcinomas are at a lower risk of further
STEVIE, an international, open-label trial. Eur J Cancer 2017;86:334- basal cell carcinomas than patients with only a basal cell carcinoma. J
348. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29073584. Am Acad Dermatol 2009;61:247-251. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/19481292.
288. Bossi P, Peris K, Calzavara-Pinton P, et al. Cohort analysis of
safety and efficacy of vismodegib in Italian patients from the Phase II, 295. Flohil SC, van der Leest RJ, Arends LR, et al. Risk of subsequent
multicenter STEVIE study. Future Oncol 2020;16:1091-1100. Available cutaneous malignancy in patients with prior keratinocyte carcinoma: a
at: https://www.ncbi.nlm.nih.gov/pubmed/32374193. systematic review and meta-analysis. Eur J Cancer 2013;49:2365-
2375. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23608733.
289. Lacouture ME, Tang JY, Rogers GS, et al. The RegiSONIC
disease registry: Preliminary effectiveness and safety in the first 66
newly diagnosed locally advanced basal cell carcinoma (BCC)
patients treated with vismodegib. ASCO Meeting Abstracts
2015;33:9023. Available at:
http://meeting.ascopubs.org/cgi/content/abstract/33/15_suppl/9023.

290. Jacobsen AA, Aldahan AS, Hughes OB, et al. Hedgehog


Pathway Inhibitor Therapy for Locally Advanced and Metastatic Basal
Cell Carcinoma: A Systematic Review and Pooled Analysis of
Interventional Studies. JAMA Dermatol 2016;152:816-824. Available
at: http://www.ncbi.nlm.nih.gov/pubmed/27096888.

291. Xie P, Lefrancois P. Efficacy, safety, and comparison of sonic


hedgehog inhibitors in basal cell carcinomas: A systematic review and
meta-analysis. J Am Acad Dermatol 2018;79:1089-1100 e1017.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/30003981.

292. Robinson JK. Follow-up and prevention (basal cell carcinoma).


In: Miller SJ, Maloney ME, eds. Cutaneous Oncology Pathophysiology,
diagnosis, and management. Malden, MA: Blackwell Science;
1998:695-698.

293. Marcil I, Stern RS. Risk of developing a subsequent


nonmelanoma skin cancer in patients with a history of nonmelanoma
skin cancer: a critical review of the literature and meta-analysis. Arch
Dermatol 2000;136:1524-1530. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/11115165.

Version 1.2023 © 2023 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-32

You might also like