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Review
Int J Gynecol Cancer: first published as 10.1136/ijgc-2024-005471 on 10 June 2024. Downloaded from http://ijgc.bmj.com/ on August 31, 2024 at International Gynecologic Cancer Society.
INTERNATIONAL JOURNAL OF
Notable surgical trials in gynecologic
GYNECOLOGICAL CANCER
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oncology: a 10-year overview
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José C Vilches ‍ ‍,1 María Clara Santía,2 Elise Mann Yates ‍ ‍,2 Rene Pareja ‍ ‍,3 Manuel Lozano,1
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ijgc.bmj.com
Pedro T Ramirez ‍ ‍2
1
Department of Obstetrics ABSTRACT with negative sentinel lymph node, it was safe to omit
and Gynecology, Hospital an inguinofemoral lymphadenectomy. GROINSS- V
In the last decade, we have witnessed important
Quironsalud Malaga, Malaga,
Spain advances in novel therapeutics in the management I3 evaluated long- term follow-up of patients who
2
Obstetrics and Gynecology, of gynecologic cancers. These studies have built on underwent sentinel lymph node mapping during the
Houston Methodist Hospital, the findings from preexisting data and have provided GROINS-V study period (2000–2006). A total of 377
Houston, Texas, USA incremental contributions leading to changes that have patients with unifocal squamous cell carcinoma of the
3
Gynecology, Gynecologic not only impacted the accuracy of cancer detection and its vulva (T1, <4 cm) were included (253 with negative
Oncology, Clinica ASTORGA, metastatic components but also led to improvements in
Medellin, and Instituto Nacional
sentinel node and 124 with positive sentinel node).
oncologic outcomes and quality of life. Key landmark trials
de Cancerología, Medellin, In patients with positive sentinel nodes, inguinofem-
have changed the standard of care in cervix, uterine, and
Colombia
ovarian cancer. A number of these have been controversial
oral lymphadenectomy was performed. The median
and have generated significant debate among gynecologic follow-up was 105 months. The 5- and 10 year recur-
Correspondence to oncologists. The main objective of this review was to rence rates for sentinel node-negative patients were
Dr José C Vilches, Department provide an overview on each of these trials as a reference 24.6% and 33.2% (p=0.03), respectively. For patients
of Obstetrics and Gynecology, for immediate and consolidated access to the study aims, with positive sentinel nodes and lymphadenectomy,
Hospital Quironsalud Malaga,
methodology, results, and conclusion. the recurrence rates were 36.4% and 46.4%, respec-
Malaga, 29004, Spain;
Protected by copyright.
jcvilches@sego.es tively (p=0.03). The rate of isolated groin recurrence
was 2.3% for patients with negative sentinel node
INTRODUCTION and 8.0% for patients with positive sentinel node after
Received 5 March 2024 During the last decade, several groundbreaking trials 5 years. Disease-specific 10 year survival was 91%
Accepted 29 May 2024
have redefined the standard of care in patients with for sentinel node-negative patients compared with
Published Online First
10 June 2024 gynecologic malignancies. These trials have not only 65% for sentinel node-positive patients (p=0.0001).
challenged established policies but have also resulted Among the study limitations, the exact location of
in significantly improved outcomes. They have paved each local recurrence was not prospectively recorded
the way for a novel approach to the decision-making and the treatment of local recurrences was at the
process for cancer patients. According to global discretion of the treating gynecologist.
cancer statistics for 2020, gynecological malignancies The authors concluded that the omission of lymph-
accounted for 16.5% of the estimated 8.2 million new adenectomy is safe in patients with unifocal vulvar
cancer cases in women worldwide.1 Over the past 10 squamous cell carcinoma tumors <4 cm without
years, there has been a significant transformation in suspicious inguinofemoral lymph nodes on clin-
this field, notably due to improved surgical techniques ical examination and imaging, in whom a negative
and innovative therapeutic approaches resulting sentinel lymph node was detected.
in major advancements. The main objective of this
review is to provide an overview of each of these
GROINSS-V II (2021)
trials. This was done for each disease site in chron-
GROINSS-V II4 was a prospective multicenter
ological order. A systematic review of key prospec-
phase-II single-
arm trial investigating inguinofem-
tive studies of gynecological surgical oncology over
oral radiotherapy as an alternative to inguinofemoral
the last 10 years was performed. The articles were
lymphadenectomy in patients with vulvar cancer and
selected based on a search in Medline, EMBASE, Web
metastatic sentinel lymph node. The study included
of Science, and the Cochrane Clinical Trials Database
patients with early- stage vulvar cancer (<4 cm)
(Table 1).
without signs of lymph node involvement on imaging
© IGCS and ESGO 2024. No
who had primary surgical treatment (local excision
commercial re-use. See rights with sentinel lymph biopsy). When the sentinel lymph
and permissions. Published by VULVAR CANCER was involved (metastasis of any size), inguinofem-
BMJ. GROINSS-V I (2016) oral radiotherapy was given (50 Gy). Patients were
To cite: Vilches JC, Santía MC, In 2008, the GROINSS-V2 study, a prospective inter- divided into two groups: those with sentinel node
Yates EM, et al. Int J Gynecol national observational study, demonstrated that in micrometastases (≤2 mm) received treatment with
Cancer 2024;34:1273–1282. patients with early-stage squamous cell vulvar cancer inguinofemoral radiotherapy (126 patients), and those
Vilches JC, et al. Int J Gynecol Cancer 2024;34:1273–1282. doi:10.1136/ijgc-2024-005471 1273

Review
Table 1 Summary of articles reviewed
Number of patients and
Trial Aim Stage interventions Results
Vulvar Cancer
GROINSS-V I Evaluate safety of omitting Early stage unifocal 253 negative sentinel node The omission of lymphadenectomy
(2016)3 an inguinofemoral squamous cell 124 positive sentinel node is safe in early-stage unifocal
lymphadenectomy carcinoma of the vulva – lymphadenectomy squamous cell carcinoma of the
(<4 cm) vulva (T1, <4 cm) with negative SLN.
GROINSS-V II Evaluate if inguinofemoral Early-stage vulvar 126 with micrometastases Inguinofemoral radiotherapy is a
(2021)4 radiotherapy is cancer (<4 cm) and (≤2 mm) inguinofemoral safe alternative in patients with
an alternative to metastatic sentinel radiotherapy sentinel node micrometastases.
inguinofemoral lymph node 105 macrometastases In patients with macrometastasis,
lymphadenectomy (>2 mm) lymphadenectomy is recommended
-lymphadenectomy
Cervical Cancer
LACC (2018)6 Compare disease-free Early-stage cervical 319 minimally invasive Minimally invasive surgery was
survival between minimally cancer (FIGO 2009 IA1 surgery (laparoscopic or associated with lower rate of
invasive and open radical with LVSI to IB1) robotic) disease-free and overall survival
hysterectomy 312 open surgery
UTERUS 11 Evaluate pre-treatment Locally advanced 130 surgical staging No difference in disease-free survival
(2020)10 surgical vs clinical staging cervical cancer (FIGO 125 clinical staging and overall survival between surgical
2009 stage IIB-IVA) and clinical staging (except for FIGO
stage IIB)
CONCERV Evaluate feasibility of cone Early-stage (FIGO 2009 42 conization Conservative surgery was safe and
(2021)11 or simple hysterectomy and stage IA2–IB1) and low- 36 conization followed by feasible in patients with early-stage
lymph node staging risk cervical cancer hysterectomy and low-risk cervical cancer
16 inadvertent simple
hysterectomy
SHAPE (2023)12 Compare disease-free Low-risk cervical 350 to radical No difference in pelvic recurrence–
survival for radical vs cancer (FIGO 2009 hysterectomy free survival, extrapelvic recurrence–
simple hysterectomy stage 1A2 or 1B1 350 to simple free survival, recurrence-free
with lesion ≤2 cm hysterectomy survival, or overall survival for simple
and <10 mm stromal hysterectomy
invasion)
Endometrial Cancer
LACE (2017)13 Compare open vs total Stage I endometrial 353 open hysterectomy Total open abdominal hysterectomy
laparoscopic hysterectomy cancer 407 laparoscopic compared with total laparoscopic
hysterectomy hysterectomy resulted in equivalent
disease-free survival and no
difference in overall survival and
recurrence.
Sentinel Lymph Node Mapping
FIRES (2017)16 Compare sensitivity and Stage I endometrial 340 received injection Sentinel lymph nodes identified
negative predictive value cancer of dye with indocyanine with indocyanine green have a
of sentinel lymph node green, attempted sentinel high degree of diagnostic accuracy
mapping with complete lymph node mapping, and in detecting endometrial cancer
lymphadenectomy in lymphadenectomy. metastases and may safely replace
detecting metastatic 97% had at least one lymphadenectomy
disease mapped sentinel lymph
node
FILM (2018)17 Evaluate if indocyanine Stage I endometrial or 87 blue dye-indocyanine Indocyanine green dye is superior
green is non-inferior to cervical cancer green to isosulfan blue dye in detecting
isosulfan blue dye in 89 indocyanine green–blue sentinel lymph nodes
detecting sentinel lymph dye
nodes.
SHREC (2019)18 Evaluate indocyanine green Stage I-II high-risk 257 pelvic sentinel lymph Pelvic sentinel lymph node algorithm
algorithm for the detection endometrial cancer node biopsy with pelvic with indocyanine green may safely
of pelvic lymph node (FIGO grade 3 lymph node dissection, replace lymphadenectomy in stage
metastases endometrioid histology, and infrarenal para-aortic I-II high-risk endometrial cancer.
non-endometrioid lymph node dissection.
histology, >50%
myometrial tumor
invasion, cervical
stromal invasion
Continued
1274 Vilches JC, et al. Int J Gynecol Cancer 2024;34:1273–1282. doi:10.1136/ijgc-2024-005471

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Table 1 Continued
19
SENTOR (2021) Evaluate sensitivity of the Stage I intermediate- 156 sentinel lymph node Sentinel lymph node biopsy
sentinel lymph node biopsy and high-grade and lymphadenectomy is comparable in diagnostic
algorithm in detecting (FIGO grade 2 or 3 101 (with high-grade) also accuracy and prognostic ability
metastatic disease. endometrioid, serous, para-aortic lymph node to lymphadenectomy in patients
carcinosarcoma, clear dissection with intermediate- and high-grade
cell, undifferentiated or endometrial carcinoma.
dedifferentiated, and
mixed) endometrial
cancer
Ovarian Cancer
NACT vs primary cytoreductive surgery
CHORUS (2015)20 Compare primary Stage III or IV ovarian 276 primary surgery Primary chemotherapy is non-inferior
surgery vs neoadjuvant cancer 274 neoadjuvant to primary surgery in overall survival
chemotherapy with primary chemotherapy and progression-free survival
endpoint of overall survival.
JCOG0602 Compare overall survival Stage III or IV ovarian 149 primary surgery Compared with primary surgery a
(2020)23 between primary cancer 152 neoadjuvant survival noninferiority of neoadjuvant
surgery and neoadjuvant chemotherapy chemotherapy was not confirmed.
chemotherapy
SCORPION Investigate whether Stage IIIC-IV ovarian 84 primary surgery No difference in overall and
(2020)24 neoadjuvant chemotherapy cancer 87 neoadjuvant progression-free survival, with
followed by surgery chemotherapy neoadjuvant chemotherapy and
is superior to primary primary cytoreductive surgery in
debulking surgery and patients with advanced epithelial
chemotherapy in terms of ovarian, fallopian tube or primary
progression-free survival peritoneal cancer (stage IIIC-IV)
OVHIPEC1 Determine whether Stage III epithelial 123 surgery without HIPEC HIPEC with interval cytoreductive
(2018)25 hyperthermic ovarian cancer 122 surgery with HIPEC surgery led to improved recurrence-
intraperitoneal free survival and overall survival
chemotherapy (HIPEC) compared with surgery alone
at interval cytoreductive
surgery after neoadjuvant
chemotherapy improved
recurrence-free survival
and overall survival
LION (2019)31 Assess efficacy of Stage IIB-IV ovarian 323 lymphadenectomy In patients with macroscopically
systematic pelvic and para- cancer 324 non- complete resection and
aortic lymphadenectomy lymphadenectomy clinically negative lymph nodes,
in patients with advanced systematic pelvic and para-
ovarian cancer and intra- aortic lymphadenectomy was
abdominal complete not associated with better overall
debulking survival and progression-free survival
compared with no lymphadenectomy
Secondary cytoreduction
GOG-213 (2019)28 Assess whether secondary Platinum-sensitive 240 secondary Secondary cytoreductive surgery
cytoreduction would recurrent ovarian cytoreduction plus followed by chemotherapy in
increase overall survival cancer with chemotherapy patients with platinum-sensitive,
among women with investigator-determined 245 chemotherapy alone recurrent ovarian cancer did not
platinum sensitive, resectable disease (84% received result in longer overall survival than
recurrent ovarian cancer bevacizumab) chemotherapy alone
SOC-1 (2021)29 Assess the efficacy of Platinum-sensitive 182 secondary Secondary cytoreductive surgery
secondary cytoreduction recurrent ovarian cytoreduction plus follow by chemotherapy improved
plus chemotherapy vs cancer with resectable chemotherapy progression-free survival with
chemotherapy alone disease according to 175 chemotherapy alone acceptable morbidity compared with
iMODEL score and (1% received chemotherapy alone. No statistically
PET-CT bevacizumab) significant difference in overall
survival.
Continued

Review
Table 1 Continued
DESKTOP III Compared overall survival Platinum-sensitive 206 secondary Secondary cytoreductive surgery
(2021)30 in recurrent ovarian cancer recurrent ovarian cytoreduction plus followed by chemotherapy resulted
patients who underwent cancer with resectable chemotherapy in longer overall survival than
surgery and chemotherapy disease according to 201 chemotherapy alone chemotherapy alone, especially in
vs chemotherapy alone AGO score (23.1% received patients with complete resection.
bevacizumab)
AGO, Arbeitsgemeinschaft Gynaekologische Onkologie; FIGO, International Federation of Gynecology and Obstetrics; LVSI, Lymphovascular space
invasion; PET-CT, Positron emission tomography-computed tomography; SLN, Sentinel lymph node.
with sentinel node macrometastases (>2 mm) underwent lymphad- 0.6%) and a higher rate of locoregional recurrence-free survival
enectomy (105 patients). (3 year rate, 94.3% vs 98.3%). The results of this trial cannot be
In patients with sentinel node micrometastases, the ipsilateral generalized to patients with “low-risk” cervical cancer because the
isolated groin recurrence rate at 2 years was 1.6%. The isolated trial was not powered to evaluate the oncologic outcomes of the
groin recurrence rate with sentinel node macrometastases at 2 two surgical approaches in that context. In addition, the study was
years was 22% in those who underwent radiotherapy and 6.9% in not designed to determine if there was a difference between the
those who underwent inguinofemoral lymphadenectomy (p=0.011). laparoscopic and robotic approaches.
Lymphedema was less frequent in the radiotherapy group compared Based on the results of the LACC trial, guidelines in gynecologic
with inguinofemoral lymphadenectomy (11% vs 23% at 12 months, oncology (the European Society of Gynaecological Oncology (ESGO),
p<0.001). Regarding the limitations, no pretreatment quality control European Society for Medical Oncology (ESMO), and the National
was conducted for radiotherapy design and planning, the use of Comprehensive Cancer Network (NCCN)7–9 recommended the open
concurrent chemotherapy for treatment was at the treating physi- abdominal approach for radical hysterectomy.
cian’s discretion, and the protocol was modified during the study to
exceed the recurrence rate in patients with sentinel node-positive UTERUS 11 (2020)
macrometastases. UTERUS 1110 was a prospective international multicenter study
This study concluded that inguinofemoral radiotherapy is a evaluating pre-treatment surgical staging vs clinical staging on
safe alternative in patients with sentinel node micrometastases. disease-free survival in patients with locally advanced cervical
However, in patients with macrometastasis, lymphadenectomy cancer. The secondary endpoint was overall survival. The design
continues to be the recommended treatment. Based on these, the included patients FIGO 2009 stage IIB- IVA, subtypes squa-
European Society of Gynaecological Oncology (ESGO) guidelines mous cell carcinoma, adenocarcinoma, or adenosquamous who
recommend that micrometastasis and isolated tumor cells can be were randomized 1:1 to surgical or clinical staging followed by
treated with postoperative radiotherapy.5 primary platinum-based chemoradiation. All patients underwent
pre-treatment imaging, including abdominal CT and/or abdom-
inal magnetic resonance imaging (MRI). A total of 255 patients
CERVICAL CANCER (surgical arm, n=130; clinical arm, n=125) were randomized. After
LACC (2018) a median follow-up of 90 months, there was no difference between
LACC6 was aphase 3 multicenter noninferiority randomized trial the groups in disease-free survival (p=0.084) and overall survival
designed to assess the rate of disease-free survival at 4.5 years (p=0.071). It should be noted that positron emission tomography-
comparing minimally invasive and open radical hysterectomy computed tomography (PET-CT) was not used routinely in the
among patients with early-stage cervical cancer. The study popu- preoperative workup due to lack of reimbursement, patients with
lation were patients with International Federation of Gynecology stage IB2 (FIGO 2009) could not be included in the protocol and
and Obstetrics (FIGO) 2009 stage IA1 with lymphovascular invasion some patients included in the surgical staging arm showed macro-
to IB1 cervical cancer and a histologic subtype of squamous cell scopic disease in the para-aortic region.
carcinoma, adenocarcinoma, or adenosquamous carcinoma. The authors concluded that in patients with locally advanced
A total of 319 patients were randomized to minimally invasive cervical cancer, there is no difference in disease-free survival and
surgery (laparoscopic or robotic) and 312 patients to open surgery. overall survival between surgical and clinical staging. However,
The rate of disease-free survival at 4.5 years was 86.0% with mini- a post-hoc analysis showed a benefit in disease-free survival for
mally invasive surgery and 96.5% with open surgery, a difference patients with FIGO stage IIB. Currently, PET-CT or chest/abdomen
of −10.6 percentage points (95% confidence interval (CI), −16.4 to computed tomography (if PET-CT is not available) is recommended
−4.7). Minimally invasive surgery was associated with a lower rate to assess nodal and distant disease.7
of disease-free survival than open surgery (3 year rate, 91.2% vs
97.1%; HR for disease recurrence or death from cervical cancer, CONCERV (2021)
3.74; 95% CI, 1.63 to 8.58, p=0.002) and was also associated CONCERV11 was a prospective, single-arm, multicenter study to
with a lower rate of overall survival (3 year rate, 93.8% vs 99.0%), evaluate the feasibility of conservative surgery in patients with
a higher rate of death from cervical cancer (3 year rate, 4.4% vs early-stage (FIGO 2009 stage IA2–IB1), low-risk cervical cancer.

Review
The inclusion criteria were squamous cell (any grade) or adenocar- invasion). Fewer urinary tract complications, better quality of life,
cinoma (grade 1 or 2) histology; tumor size <2 cm; no lymphovas- and sexual-function were observed with simple hysterectomy.
cular space invasion; depth of invasion <10 mm; negative imaging
for metastatic disease; and negative conization margins. Eligible
patients desiring fertility preservation underwent a conization with ENDOMETRIAL CANCER
pelvic lymph node assessment. Those not desiring fertility preser- LACE (2017)
vations underwent simple hysterectomy with lymph node assess- LACE 13 was a was a multinational, phase 3, randomized equiva-
ment. lence trial. Patients with clinical stage I endometrial cancer were
A total of 100 patients were included in the study. The median randomized to undergo open abdominal hysterectomy (with or
follow-up was 36.3 months. The rate of positive lymph nodes was without lymphadenectomy) or total laparoscopic hysterectomy
5%, and the rate of residual disease in the hysterectomy specimen (with or without lymphadenectomy). The primary outcome was
following conization was 2.5%. The 2 year recurrence rate was disease-free survival. Secondary outcomes included disease recur-
3.5% overall; 2.4% (1/42) among patients who had conization, 0% rence, patterns of recurrence, and overall survival. Patients were
(0/36) among patients who had conization followed by hysterec- followed for a median of 4.5 years.
tomy, and 12.5% (2/16) among patients who had an inadvertent Of 760 randomized patients (353 to open abdominal hysterec-
simple hysterectomy. tomy and 407 to laparoscopic hysterectomy), 679 (89%) completed
It is important to mention that lymph node evaluation and the the trial. The disease-free survival was 81.3% in the open abdom-
choice of surgical approach was based on surgeon preference inal hysterectomy group and 81.6% in the total laparoscopic hyster-
and training. The inclusion criteria were modified during the trial, ectomy group (difference: 0.3% [95% CI, −5.5% to 6.1%], favoring
prompted by three patients who developed recurrent disease, total laparoscopic hysterectomy, p=0.007). There were no statisti-
adding requirements for depth of invasion <10 mm and negative cally significant differences between groups in terms of recurrence
cone margins for high-grade dysplasia. (difference: 0.2% [95% CI, −3.7% to 4.0%]; p=0.93) or overall
This study was the first of three (SHAPE12 and GOG 278 survival (difference: 0.6% [95% CI, −3.0% to 4.2%]; p=0.76).
NCT01649089) showing the feasibility and safety of conservative Some weaknesses of the study were that the randomization was
surgery in patients with early-stage (FIGO 2009 stage IA2–IB1) and performed before the patient was scheduled for surgery. Moreover,
low-risk cervical cancer.
performance of pelvic and aortic retroperitoneal node dissection
was left to the discretion of the surgeons. Otherwise, the study
SHAPE (2023) only included patients with endometrial tumors with endometroid
SAPHE12 was a phase 3, multicenter, noninferiority, randomized histology.
trial comparing radical hysterectomy with simple hysterectomy The authors concluded that total open abdominal hysterectomy
including lymph- node assessment in low- risk cervical cancer. compared with total laparoscopic hysterectomy in stage I endo-
Patients were eligible if they had squamous-cell carcinoma, adeno- metrial cancer resulted in equivalent disease-free survival and no
carcinoma, or adenosquamous carcinoma; FIGO 2009 stage 1A2 difference in overall survival and recurrence. This study supported
or 1B1 with lesion ≤2 cm and limited stromal invasion (<10 mm on those of the previously published landmark study (GOG-LAP2),14
LEEP/cone or <50% on preoperative MRI). The primary outcome confirming the standard being laparoscopic hysterectomy for
was pelvic recurrence rate at 3 years. Secondary outcomes patients with stage I endometrial cancer.15
included pelvic recurrence-free survival, extrapelvic recurrence-
free survival, recurrence-free survival, overall survival, adverse Sentinel lymph node mapping
events, and quality of life.
A total of 700 patients underwent randomization, 350 to radical FIRES (2017)
hysterectomy and 350 to simple hysterectomy. With a median FIRES16 was a multicenter, prospective cohort study comparing the
follow-up of 4.5 years, the incidence of pelvic recurrence at 3 years sensitivity and negative predictive value of sentinel lymph node
was 2.2% in the radical hysterectomy group and 2.5% in the simple mapping with complete lymphadenectomy in detecting metastatic
hysterectomy group (an absolute difference of 0.35 percentage disease for endometrial cancer.
points; 90% CI, −1.62 to 2.32). There was no apparent associa- A total of 385 patients with clinical stage I endometrial cancer
tion between treatment group and pelvic recurrence–free survival, of all histologic subtypes and grades undergoing robotic staging
extrapelvic recurrence–free survival, recurrence- free survival, were included. Of those, 340 patients received injection of dye with
or overall survival. Radical hysterectomy was associated with a indocyanine green, attempted sentinel lymph node mapping, and
significantly higher incidence of urinary incontinence (p=0.003) lymphadenectomy. Of these, 41 (12%) patients had positive nodes.
and urinary retention (p=0.0001). Quality of life scores showed a Nodal metastases were identified in the sentinel lymph nodes of
significant difference between the two groups in favor of simple 35/36 (97%) patients who had at least one mapped sentinel lymph
hysterectomy. The trial was designed before the results of the LACC node, yielding a sensitivity to detect node-positive disease of 97.2%
trial and was not designed to determine the safety of the surgical (95% CI 85 to 100). Twenty-one (60%) of 35 patients with positive
approach (minimally invasive vs open) in this very low-risk popula- sentinel lymph nodes had disease limited to the sentinel lymph
tion. In addition, the surgical approach was chosen by the surgeons. nodes, and 14 (40%) patients had additional positive nodes in their
Based on these findings, simple hysterectomy is not inferior nonsentinel lymph node specimens. Among the 258 patients with
to radical hysterectomy in patients with low-risk cervical cancer negative sentinel lymph nodes, 257 had truly negative nonsentinel
(FIGO 2009 stage 1A2 or 1B1 with lesion ≤2 cm and limited stromal lymph nodes, resulting in a negative predictive value of 99.6%

Review
(95% CI 97.9 to 100). Some limitations of the study were that only lymph node biopsy with pelvic lymph node dissection, and infra-
28% of patients had high-grade histologic subtypes, the study renal para-aortic lymph node dissection.
was unable to determine morbidity or oncological outcomes, and Fifty-four patients (21%) of 257 had pelvic lymph node metas-
performing para-aortic lymphadenectomy was at the discretion of tases, and 52 (20%) were correctly identified by the sentinel lymph
each surgeon. node indocyanine green algorithm. This had a sensitivity to identify
Based on this study, sentinel lymph nodes identified with indocy- pelvic lymph node metastases of 98% (95% CI 89 to 100) and a
anine green have a high degree of diagnostic accuracy in detecting negative predictive value of 99.5% (95% CI 97 to 100). The corre-
endometrial cancer metastases and may safely replace lymph- sponding values for the sentinel lymph node overall algorithm were
adenectomy in the staging of endometrial cancer. Although sentinel 100% (95% CI 92 to 100) and 100% (95% CI 98 to 100). Before
lymph node biopsy did not identify metastases in 3% of patients and after reinjection, the bilateral mapping rate was 82% and 95%,
with node-positive disease, it may expose fewer patients to the respectively. The para-aortic lymph node dissection was performed
morbidity of a complete lymphadenectomy. in 208 (81%) patients, and only two (1%) patients had isolated para-
aortic metastases. No adverse events occurred during the sentinel
FILM (2018) lymph node procedure. It should be noted that only 49% of patients
FILM17 was a international, multicentre, randomized, open-label, had high-grade histologic subtypes and that algorithm should, in
phase 3, non-inferiority study. A total of 180 patients with clinical the author’s opinion, be performed at high-volume centers by high-
stage I endometrial or cervical cancer undergoing surgery were volume surgeons.
randomized 1:1 to lymphatic mapping with isosulfan blue dye (visu- The authors concluded that pelvic sentinel lymph node algo-
alized by white light) followed by indocyanine green (visualized by rithm may safely replace lymphadenectomy in stage I-II high-risk
near-infrared imaging) or indocyanine green followed by isosulfan endometrial cancer without the need for para-aortic dissection. The
blue dye, of whom 176 patients received the intervention and were pelvic sentinel lymph node algorithm is supported by a lower rate
evaluable. In total, 169 (96%) of 176 patients had uterine cancer, of isolated para-aortic metastases (1%).
and seven (4%) had cervical cancer. The primary endpoint was the
efficacy of intraoperative indocyanine green with near-infrared fluo- SENTOR (2021)
rescence imaging vs that of blue dye in identifying lymph nodes. SENTOR19 was a prospective, multicenter cohort study to eval-
In total, 471 (97%) of 485 lymph nodes were identified with the uate the sensitivity of the sentinel lymph node biopsy algorithm in
green dye and 226 (47%) with the blue dye (difference 50%, 95% CI patients with intermediate- and high-grade (FIGO stage I, grade 2 or
39 to 62; p<0.0001). The rate of detection of at least one sentinel 3 endometrioid, serous, carcinosarcoma, clear cell, undifferentiated
node showed a difference of 22% (95% CI 17 to 32; p<0.0001), and or dedifferentiated, and mixed) endometrial cancer. Only 28% in the
the rate of bilateral sentinel nodes detection showed a difference FIRES16 trial and 49% in the SHREC18 trial had high-grade histologic
of 49% (41–57; p<0.0001) in favor of green dye. Only 16 (9%) of subtypes. The primary endpoint was the sensitivity of the sentinel
176 patients had metastatic disease in 21 sentinel nodes; 13 (62%) lymph node biopsy algorithm in detecting metastatic disease.
detected both blue and green, and eight (38%) only with green. Patients received a standard algorithm for sentinel lymph node
No allergic reactions or adverse events were attributable to either and then underwent the reference standard of lymphadenectomy;
isosulfan blue dye or indocyanine green. Among the weaknesses grade 2 endometrioid endometrial cancer required bilateral pelvic
of the study were the inability to determine sensitivity, negative lymph node dissection, and high-grade endometrial cancer required
predictive value, and oncologic outcomes for lymphatic mapping bilateral pelvic lymph node dissection and para-aortic lymph node
and sentinel node biopsy. dissection. Patients with grade 2 endometrioid endometrial cancer
The authors concluded that indocyanine green is superior to underwent para-aortic lymph node dissection only when a sentinel
isosulfan blue dye in detecting sentinel lymph nodes. The use of lymph node mapped to the para-aortic region or when the surgeon
indocyanine green dye and isosulfan blue together was unneces- deemed it necessary.
sary because adding isosulfan blue dye to indocyanine green was Sentinel lymph node detection rates were 97.4% per patient
not shown to identify more nodes beyond those identified with (95% CI, 93.6% to 99.3%), 87.5% per hemipelvis (95% CI, 83.3%
indocyanine green alone. Based on these findings, the US Food to 91.0%), and 77.6% bilaterally (95% CI, 70.2% to 83.8%). Of 27
and Drug Administration (FDA) approved the use of green dye in patients (17%) with nodal metastases, 26 patients were correctly
lymphatic mapping in gynecologic oncology. identified by the sentinel lymph node biopsy algorithm, yielding a
sensitivity of 96% (95% CI, 81% to 100%), a false-negative rate
SHREC (2019) of 4% (95% CI, 0% to 19%), and a negative predictive value of
SHREC18 was a prospective non- randomized trial evaluating 99% (95% CI, 96% to 100%). Only one patient (0.6%) was misclas-
the diagnostic accuracy of a surgically and anatomically defined sified by the sentinel lymph node biopsy algorithm. Fourteen
sentinel lymph node indocyanine green algorithm and overall patients with node-positive disease (52%) had metastatic disease
sentinel lymph node algorithm for the detection of pelvic lymph in sentinel lymph nodes only, and seven cases (26%) were found
node metastases in women with high-risk endometrial cancer. A outside lymphadenectomy boundaries or required immunohisto-
total of 257 patients with stage I-II high-risk endometrial cancer chemistry for diagnosis. These patients would not have been iden-
(FIGO grade 3 endometrioid histology, non-endometrioid histology, tified by pelvic lymph node dissection and para-aortic lymph node
>50% myometrial tumor invasion, cervical stromal invasion or, until dissection alone. The estimates of diagnostic accuracy may not be
February 14, 2017, a non-diploid cytometry) were assessed for generalizable to less experienced surgeons and centers, to sentinel
eligibility. Patients underwent robotic hysterectomy, pelvic sentinel lymph node biopsy with different types of tracers, or to patients

Review
in whom pelvic lymph node dissection or para-aortic lymph node histological confirmation, and the sample size was smaller than in
dissection may not be feasible. previous studies. Complete resection was achieved in only 12% of
The study concluded that sentinel lymph node biopsy is compa- patients in the primary surgery group and in 64% of patients in the
rable in diagnostic accuracy and prognostic ability to lymphadenec- neoadjuvant group.
tomy in patients with intermediate- and high-grade endometrial This study is the third (EORTC 5597121 and CHORUS20 to assess
carcinoma. the role of neoadjuvant therapy for stage III/IV ovarian, tubal, and
peritoneal cancers. The study authors did not confirm the noninfe-
riority of neoadjuvant chemotherapy and suggested that it may not
OVARIAN CANCER always be a substitute for primary debulking surgery.
Neoadjuvant therapy vs primary cytoreductive surgery
SCORPION (2020)
CHORUS (2015) SCORPION24 was a open-label, randomized phase III trial designed
CHORUS20 was a phase 3, non-inferiority, randomized, controlled to investigate whether neoadjuvant chemotherapy followed by
trial comparing primary chemotherapy followed by delayed surgery interval debulking surgery was superior to primary debulking
vs surgical debulking followed by chemotherapy in patients with surgery in terms of perioperative complications and progression-
suspected stage III or IV ovarian cancer. The primary outcome free survival in advanced epithelial ovarian, fallopian tube, or
measure was overall survival. Inclusion criteria were patients with primary peritoneal cancer. The study included patients with FIGO
clinical or imaging evidence of a pelvic mass with extrapelvic stage IIIC-IV with high tumor load assessed by a standardized lapa-
disease compatible with FIGO 1988 stage III or IV ovarian, fallopian roscopic predictive index, (ECOG) performance status 0–2, and
tube, or primary peritoneal cancer who were candidates for surgery chemotherapy naïve.
and chemotherapy. Of the 550 eligible patients, 276 were assigned A total of 171 patients were randomly 1:1 assigned to primary
to primary surgery and 274 to primary chemotherapy. debulking surgery (n=84) vs neoadjuvant chemotherapy, followed
Median overall survival was 22.6 months in the primary surgery by interval debulking surgery and adjuvant chemotherapy (n=87).
group vs 24.1 months in primary chemotherapy. The HR for death Complete resection rates (R0) were 47.6% in the surgery arm vs
was 0.87 in favor of primary chemotherapy (with the upper bound 77.0% in the neoadjuvant arm (p=0.001). In total, 53 major post-
of the one-sided 90% CI 0.98 [95% CI 0.72 to 1.05]). Progression- operative complications were registered, 25.9% in the surgery
free survival was similarly in favor of the primary chemotherapy arm vs 7.6% in the neoadjuvant arm (p=0.0001). With an overall
group, with medians of 12.0 months vs 10.7 months for the primary median follow-up of 59 months, the median progression-free and
surgery group. The HR for progression-free survival was 0.91 (95% overall survival were 15 and 41 months for patients assigned to
CI 0.76 to 1.09). The primary surgery group had more grade 3 or primary debulking surgery, compared with 14 and 43 months for
4 adverse events than the primary chemotherapy group (60 [24%] patients assigned to neoadjuvant chemotherapy, respectively (HR
vs 30 [14%], p=0.007). Additionally, there were more postopera- 1.05, 95% CI 0.77 to 1.44, p=0.73; HR 1.12, 95% CI 0.76 to 1.65,
tive deaths in the primary surgery group within 28 days than in p=0.56). It should be noted that the sample size was smaller than
the primary chemotherapy group (14/255 patients [6%] vs 1/219 in previous studies, BRCA status was not recorded, some patients
patients [<1%], p=0.001). It is important to mention that 59% of received treatment with bevacizumab once the trial started, and
patients had suboptimal primary surgery, moreover, the rate of some patients received four cycles of neoadjuvant chemotherapy.
complete resection was low in both groups. This is the fourth study (EORTC 55971,21 CHORUS,20 and
This study was the second prospective trial (after EORTC 5597121 JCOG060223 to assess this topic and the third (EORTC 5597121 and
to investigate the timing of surgery in the first-line treatment of CHORUS20 to show no difference in overall and progression-free
advanced ovarian cancer. These two trials confirmed that in patients survival, with neoadjuvant chemotherapy and primary cytoreduc-
with stage III or IV ovarian cancer, primary chemotherapy is non- tive surgery in patients with advanced epithelial ovarian, fallopian
inferior to primary surgery, and surgical morbidity and mortality tube or primary peritoneal cancer (stage IIIC-IV).
were significantly reduced.22
Hyperthermic intraperitoneal chemotherapy (HIPEC)
JCOG0602 (2020)
JCOG60223 was a open-label phase III noninferiority randomized OVHIPEC1 (2018)
trial designed to compare primary debulking surgery and neoadju- OVHIPEC125 was a multicenter, open-label, phase 3 trial to deter-
vant chemotherapy in patients with stage III/IV ovarian, tubal, and mine whether hyperthermic intraperitoneal chemotherapy (HIPEC)
peritoneal cancers with overall survival as the primary objective. at interval cytoreductive surgery after neoadjuvant chemotherapy
A total of 301 patients were randomized, with 149 undergoing improved recurrence-free survival and overall survival in patients
primary debulking surgery and 152 receiving neoadjuvant chemo- with stage III epithelial ovarian cancer. Disease recurrence or death
therapy. The median overall survival was 49.0 months in primary occurred in 110 of 123 patients (89%) who underwent cytore-
debulking surgery and 44.3 months in neoadjuvant chemotherapy ductive surgery without HIPEC (surgery group) and in 99 of 122
(HR of neoadjuvant chemotherapy compared with primary surgery patients (81%) who underwent cytoreductive surgery with HIPEC
was 1.05 [95% CI 0.84 to 1.33], p=0.24). The median progression- (surgery-plus-HIPEC group) (HR for disease recurrence or death,
free survival was 15.1 months in the primary debulking surgery 0.66 [95% CI 0.50 to 0.87] p=0.003). Adverse events (grade 3 or 4)
and 16.4 in the neoadjuvant chemotherapy (HR: 0.96 [95% CI 0.75 were similar in the two groups (25% in the surgery group and 27%
to 1.23]). Among the study limitations, the protocol did not require in the surgery-plus-HIPEC group, p=0.76). No differences were

Review
found between the two groups in health-related quality of life. The overall survival (chemotherapy objective) and that secondary
trial did not take into account certain factors such as BRCA status, surgical cytoreduction in platinum-sensitive, surgically amenable
FIGO tumor sub-stage III, response, or histological tumor type. The patients improved overall survival (surgical objective).
rates of progression-free survival and overall survival with HIPEC The study included patients with recurrent ovarian cancer who
were similar to the rates among patients with interval debulking had received one previous therapy, had a platinum-free interval of
without HIPEC. 6 months or more, had investigator-determined resectable disease
In patients with stage III epithelial ovarian cancer, HIPEC with to undergo secondary surgical cytoreduction, and then received
interval cytoreductive surgery led to greater recurrence- free platinum-based chemotherapy or received platinum-based chemo-
survival and overall survival compared with surgery alone, without therapy alone. Adjuvant chemotherapy (paclitaxel-carboplatin or
increased incidence of side effects. The NCCN guidelines suggest gemcitabine-carboplatin) and use of bevacizumab were at the
that HIPEC can be considered during interval surgery on patients discretion of the investigator.
with stage III disease after neoadjuvant chemotherapy. However, at A total of 485 patients were included. Of these, 240 patients
the ESGO-ESMO-ESP consensus conference, experts failed to reach were randomized to secondary cytoreduction before chemotherapy
a consensus, highlighting the current divergence of opinions.26 27 and 245 to chemotherapy alone. The median follow-up was 48.1
months. The median overall survival was 50.6 months for surgery
Lymph node and 64.7 months for no surgery (HR death for surgery vs no surgery
was 1.29 [95% CI 0.97 to 1.72] p=0.08). Adjustments for platinum-
LION (2019)
free interval and chemotherapy choice did not alter the effect. The
LION26 was a randomized controlled trial investigating systematic
HR for disease progression or death (surgery vs no surgery) was
lymphadenectomy in patients with primary ovarian cancer (FIGO
0.82 (95% CI, 0.66 to 1.01: median progression-free survival, 18.9
stage IIB through IV) who underwent complete macroscopic resec-
months and 16.2 months, respectively).
tion and had normal lymph nodes both before and during surgery.
It should be noted that the study had no defined patient eligi-
The primary outcome was overall survival.
bility criteria for surgery, there was a lack of data on the extent
Patients were randomized to either lymphadenectomy (pelvic
of residual disease after primary debulking surgery and it remains
and para-aortic) or no lymphadenectomy. A total of 627 patients
unclear how many patients from the non-surgical group crossed
were included, 323 in the lymphadenectomy group and 324 in the
over and received surgery later.
non-lymphadenectomy group. The median overall survival was
The authors concluded that secondary cytoreductive surgery
69.2 months in the no-lymphadenectomy group and 65.5 months
followed by chemotherapy in patients with platinum- sensitive,
in the lymphadenectomy group (HR for death in the lymphadenec-
recurrent ovarian cancer did not result in longer overall survival
tomy group, 1.06 [95% CI 0.83 to 1.34; p=0.65]), and median
than chemotherapy alone.
progression-free survival was 25.5 months in both groups (HR for
progression or death in the lymphadenectomy group, 1.11 [95% CI,
SOC-1 (2021)
0.92 to 1.34] p=0.29). Postoperative complications occurred more
SOC-1 29 was a multicentre, open-label, randomized, controlled,
frequently in the lymphadenectomy group. Repeat laparotomy was
phase 3 trial to assess the efficacy of secondary cytoreduction plus
12.4% in the lymphadenectomy group compared with 6.5% in the
chemotherapy vs chemotherapy alone in patients with platinum-
non-lymphadenectomy group (p=0.01), while mortality within 60
sensitive relapsed ovarian cancer. The primary endpoints were
days was 3.1% vs 0.9% (p=0.049), respectively.
progression-free survival and overall survival. Patients aged 18
Some limitations of this study need to be considered: the low
years and older with a platinum-free interval of at least 6 months
average number of patients per center, a selection bias as only
and potentially resectable disease according to the international
patients with preserved performance status and radiologically
model (iMODEL) score and PET- CT imaging were eligible. An
negative lymph nodes were included and lack of information on
iMODEL score of 4.7 or lower predicted a potentially complete
prognostic factors in advanced ovarian cancer. Finally, the definition
resection. In total, 357 patients were recruited and randomly
of a clinically negative lymph node was imprecise, as there may
assigned to the surgery group (182) or the no-surgery group (175).
not always be a clear size difference between metastatic and non-
The median follow-up was 36.0 months.
metastatic nodes.
Median progression-free survival was 17.4 months (95% CI 15.0
The authors concluded that in patients with macroscopically
to 19.8) in the surgery group and 11.9 months (10.0–13.8) in the
complete resection of advanced ovarian cancer and clinically nega-
no-surgery group (HR 0.58 [95% CI 0.45 to 0.74] p<0.0001). A
tive lymph nodes, systematic pelvic and para-aortic lymphadenec-
prespecified interim overall survival analysis showed no statistically
tomy is not associated with better outcomes compared with no
significant difference between both groups. Median overall survival
lymphadenectomy and was associated with a higher incidence of
was 58.1 months (95% CI not estimable) in the surgery group and
postoperative complications.
53.9 months (42.2–65.5) in the no-surgery group (HR 0.82 [95% CI
Secondary cytoreduction 0.57 to 1.19]). It is important to mention that only 1% of patients
received bevacizumab and 37% of patients in the no-surgery group
GOG-213 (2019) crossed over to surgery at subsequent relapse.
GOG-21328 was an open-label, phase 3, multicenter, international, Secondary cytoreduction followed by chemotherapy improved
randomized clinical trial designed to assess two clinically relevant progression-free survival with acceptable morbidity compared with
hypotheses: that bevacizumab added to paclitaxel and carboplatin chemotherapy alone for patients with platinum-sensitive, relapsed
chemotherapy followed by maintenance bevacizumab improved ovarian cancer selected using iMODEL scores and PET-CT imaging.

Review
DESKTOP III (2021) Patient consent for publication Not applicable.
Desktop III30 was a multicenter prospectively randomized trial to Ethics approval Not applicable.
assess the role of secondary cytoreductive surgery in patients Provenance and peer review Not commissioned; externally peer reviewed.
with recurrent ovarian cancer. The primary outcome was overall
ORCID iDs
survival. The inclusion criteria were patients with relapsed histo- José C Vilches http://orcid.org/0000-0003-0460-9457
logically diagnosed, clinically defined as a lesion that is palpable Elise Mann Yates http://orcid.org/0009-0002-4933-0986
or visible on ultrasonographic imaging, or relapsed disease radio- Rene Pareja http://orcid.org/0000-0003-0093-0438
logically diagnosed at least 6 months after the previous course of Pedro T Ramirez http://orcid.org/0000-0002-6370-8052
initial platinum-based chemotherapy (platinum-sensitive disease)
and a positive Arbeitsgemeinschaft Gynaekologische Onkologie
(AGO) score. REFERENCES
In total, 407 participants were randomly assigned to either 1 Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020:
GLOBOCAN estimates of incidence and mortality worldwide for 36
chemotherapy alone (n=201) or cytoreductive surgery and chemo- cancers in 185 countries. CA Cancer J Clin 2021;71:209–49.
therapy (n=206). Of those who underwent surgery, 75.5% achieved 2 Van der Zee AGJ, Oonk MH, De Hullu JA, et al. Sentinel node
a complete resection. Median overall survival was 53.7 months for dissection is safe in the treatment of early-stage vulvar cancer. J Clin
Oncol 2008;26:884–9.
the surgery group and 46.0 months for the no-surgery group (HR 3 Te Grootenhuis NC, van der Zee AGJ, van Doorn HC, et al. Sentinel
for death, 0.75 [95% CI, 0.59 to 0.96] p=0.02). However, among nodes in vulvar cancer: long-term follow-up of the Groningen
international study on sentinel nodes in vulvar cancer (GROINSS-V)
the patients assigned to the surgery group, those who achieved a I. Gynecol Oncol 2016;140:8–14.
complete resection had a median overall survival of 61.9 months. 4 Oonk MHM, Slomovitz B, Baldwin PJW, et al. Radiotherapy versus
Quality of life measures through 1 year of follow-up did not differ Inguinofemoral lymphadenectomy as treatment for vulvar cancer
patients with micrometastases in the sentinel node: results of
between the two groups. Among the study limitations only 23.1% GROINSS-V II. J Clin Oncol 2021;39:3623–32.
of patients received bevacizumab, there were different distributions 5 Oonk MHM, Planchamp F, Baldwin P, et al. European society
of gynecological oncology guidelines for the management of
of histological subtypes in both arms, the percentage of complete patients with vulvar cancer - update 2023. Int J Gynecol Cancer
cytoreduction was higher than that published in other studies and 2023;33:1023–43.
6 Ramirez PT, Frumovitz M, Pareja R, et al. Minimally invasive versus
the survival benefit was only observed in those patients in whom abdominal radical hysterectomy for cervical cancer. N Engl J Med
R0 was achieved. 2018;379:1895–904.
The authors concluded that in patients with recurrent ovarian 7 Cibula D, Raspollini MR, Planchamp F, et al. ESGO/ESTRO/ESP
guidelines for the management of patients with cervical cancer –
cancer, secondary cytoreductive surgery followed by chemotherapy update 2023. Int J Gynecol Cancer 2023;33:649–66.
resulted in longer overall survival than chemotherapy, especially in 8 Marth C, Landoni F, Mahner S, et al. Cervical cancer: ESMO clinical
practice guidelines for diagnosis, treatment and follow-up. Ann
those patients in whom complete resection surgery was achieved. Oncol 2017;28:iv72–83.
9 Abu-Rustum NR, Yashar CM, Arend R, et al. NCCN clinical practice
guidelines in oncology: cervical cancer. Version 1. 2024.
10 Marnitz S, Tsunoda AT, Martus P, et al. Surgical versus clinical
staging prior to primary chemoradiation in patients with cervical
CONCLUSION cancer FIGO stages IIB-IVA: oncologic results of a prospective
randomized International multicenter (Uterus-11) Intergroup study.
Over the past 10 years we have witnessed significant advances in Int J Gynecol Cancer 2020;30:1855–61.
the treatment of vulvar, cervical, endometrial, and ovarian tumors. 11 Schmeler KM, Pareja R, Lopez Blanco A, et al. ConCerv: a
The emergence of techniques such as sentinel lymph node sampling, prospective trial of conservative surgery for low-risk early-stage
cervical cancer. Int J Gynecol Cancer 2021;31:1317–25.
the decreased emphasis on radicality in the treatment of cervical 12 Plante M, Kwon JS, Ferguson S, et al. Simple versus radical
cancer, and the incorporation of neoadjuvant therapy for ovarian hysterectomy in women with low-risk cervical cancer. N Engl J Med
2024;390:819–29.
cancer are evidence of this shift. Our ultimate objective remains to 13 Janda M, Gebski V, Davies LC, et al. Effect of total laparoscopic
offer patients the best possible outcomes in terms of survival and hysterectomy vs total abdominal hysterectomy on disease-
disease-free survival with the lowest possible morbidity. Our field is free survival among women with stage I endometrial cancer: a
randomized clinical trial. JAMA 2017;317:1224–33.
moving toward less radical procedures with improved perioperative 14 Walker JL, Piedmonte MR, Spirtos NM, et al. Recurrence and
outcomes. Similarly, it is essential for future prospects, that treat- survival after random assignment to laparoscopy versus laparotomy
for comprehensive surgical staging of uterine cancer: gynecologic
ments are tailored to patients' characteristics, fertility preferences oncology group LAP2 study. J Clin Oncol 2012;30:695–700.
and resources. Future advances in imaging technologies, including 15 Concin N, Matias-Guiu X, Vergote I, et al. ESGO/ESTRO/ESP
guidelines for the management of patients with endometrial
3D models and artificial intelligence, will likely expand our capabil- carcinoma. Int J Gynecol Cancer 2021;31:12–39.
ities toward more targeted surgical options. 16 Rossi EC, Kowalski LD, Scalici J, et al. A comparison of sentinel
lymph node biopsy to lymphadenectomy for endometrial cancer
X María Clara Santía @claritasantia, Rene Pareja @RParejaGineOnco and Pedro T staging (FIRES trial): a multicentre, prospective, cohort study. Lancet
Oncol 2017;18:384–92.
Ramirez @pedroramirezMD 17 Frumovitz M, Plante M, Lee PS, et al. Near-infrared fluorescence
Contributors JCV: conceptualization, investigation, writing original draft, writing for detection of sentinel lymph nodes in women with cervical and
review and editing. MCS: investigation, writing original draft, writing review and uterine cancers (FILM): a randomised, phase 3, multicentre, non-
editing. EMY: investigation, review and editing. RP: investigation, writing review inferiority trial. Lancet Oncol 2018;19:1394–403.
18 Persson J, Salehi S, Bollino M, et al. Pelvic sentinel lymph node
and editing. ML: investigation, writing review and editing. PTR: conceptualization, detection in high-risk endometrial cancer (SHREC-Trial)-The final
investigation, writing review and editing, project administration, project supervision. step towards a paradigm shift in surgical staging. Eur J Cancer
Funding The authors have not declared a specific grant for this research from any 2019;116:77–85.
funding agency in the public, commercial or not-for-profit sectors. 19 Cusimano MC, Vicus D, Pulman K, et al. Assessment of sentinel
lymph node biopsy vs lymphadenectomy for intermediate- and high-
Competing interests None declared. grade endometrial cancer staging. JAMA Surg 2021;156:157–64.

Review
20 Kehoe S, Hook J, Nankivell M, et al. Primary chemotherapy versus 26 Armstrong DK, Alvarez RD, Backes FJ, et al. NCCN clinical practice
primary surgery for newly diagnosed advanced ovarian cancer guidelines in oncology: ovarian cancer, including Fallopian tube
(CHORUS): an open-label, randomised, controlled, non-inferiority cancer and primary peritoneal cancer. Version 2. 2023.
trial. Lancet 2015;386:249–57. 27 Ledermann JA, Matias-Guiu X, Amant F, et al. ESGO–ESMO–ESP
21 Vergote I, Tropé CG, Amant F, et al. Neoadjuvant chemotherapy consensus conference recommendations on ovarian cancer:
or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med
pathology and molecular biology and early, advanced and recurrent
2010;363:943–53.
22 Colombo N, Sessa C, du Bois A, et al. ESMO-ESGO consensus disease. Ann Oncol 2024;35:248–66.
conference recommendations on ovarian cancer: pathology and 28 Coleman RL, Spirtos NM, Enserro D, et al. Secondary surgical
molecular biology, early and advanced stages, borderline tumours cytoreduction for recurrent ovarian cancer. N Engl J Med
and recurrent disease. Ann Oncol 2019;30:672–705. 2019;381:1929–39.
23 Onda T, Satoh T, Ogawa G, et al. Comparison of survival between 29 Shi T, Zhu J, Feng Y, et al. Secondary cytoreduction followed by
primary debulking surgery and neoadjuvant chemotherapy for stage chemotherapy versus chemotherapy alone in platinum-sensitive
III/IV ovarian, Tubal and peritoneal cancers in phase III randomised Relapsed ovarian cancer (SOC-1): a multicentre, open-label,
trial. Eur J Cancer 2020;130:114–25. randomised, phase 3 trial. Lancet Oncol 2021;22:439–49.
24 Fagotti A, Ferrandina MG, Vizzielli G, et al. Randomized trial of
30 Harter P, Sehouli J, Vergote I, et al. Randomized trial of
primary debulking surgery versus neoadjuvant chemotherapy for
cytoreductive surgery for relapsed ovarian cancer. N Engl J Med
advanced epithelial ovarian cancer (SCORPION-NCT01461850). Int
J Gynecol Cancer 2020;30:1657–64. 2021;385:2123–31.
25 van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic 31 Harter P, Sehouli J, Lorusso D, et al. A randomized trial of
intraperitoneal chemotherapy in ovarian cancer. N Engl J Med lymphadenectomy in patients with advanced ovarian neoplasms.
2018;378:230–40. N Engl J Med 2019;380:822–32.

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