Research

JAMA Oncology | Original Investigation

Update of Incidence, Prevalence, Survival, and Initial Treatment

in Patients With Non–Small Cell Lung Cancer in the US
Apar Kishor Ganti, MD; Alyssa B. Klein, MPH; Ion Cotarla, MD, PhD; Brian Seal, RPh, MBA, PhD; Engels Chou, MS

Editorial page 1765

IMPORTANCE Updated estimates of non–small cell lung cancer (NSCLC) in the US are needed. Related article page 1833
OBJECTIVE To calculate the most recent epidemiologic estimates of NSCLC in the US. Supplemental content
DESIGN, SETTING, AND PARTICIPANTS This cross-sectional epidemiological analysis used the
most recently released data from US cancer registries. The population-based US Cancer
Statistics (USCS) database (2010-2017), comprised of the Surveillance, Epidemiology,
and End Results (SEER) program and the National Program of Cancer Registries (NPCR)
(collectively, SEER-NPCR) provided the NSCLC incidence estimate. The SEER-18 database
provided data for incidence, prevalence, survival, and initial treatment by NSCLC stage.
Adults aged 18 years or older diagnosed with NSCLC identified by International Classification
of Diseases for Oncology, Third Edition, morphology codes were included.

MAIN OUTCOMES AND MEASURES Annual age-adjusted NSCLC incidence per 100 000
persons; annual prevalence per 100 000 persons; survival rate; initial treatment. Due to
database release delays, incidence data were available through 2017, and other parameters
through 2016. The analysis was conducted from June 2020 to July 2020.

RESULTS There were 1.28 million new NSCLC cases recorded during 2010 to 2017 in the US
(SEER-NPCR: 53% male; 67% ⱖ 65 years). From 2010 to 2017, NSCLC incidence per 100 000
decreased from 46.4 to 40.9 overall (age <65 years: 15.5 to 13.5; age ⱖ65 years: 259.9 to
230.0); the incidence of stage II, IIIA, and IIIB NSCLC was stable, and stage IV decreased
slightly from 21.7 to 19.6, whereas stage I incidence increased from 10.8 to 13.2. From 2010 to
2016, NSCLC prevalence per 100 000 increased from 175.3 to 198.3 (nationwide projection
of SEER-18); prevalence increased among younger patients (77.5 to 87.9) but decreased
among older patients (825.1 to 812.4). Period survival analysis found that 26.4% of patients
survived 5 years, which is higher than previously reported. The proportion of stage I NSCLC
treated with radiation as single initial treatment rose markedly from 14.7% in 2010
to 25.7% in 2016. Patients with stage IV NSCLC aged 65 years or older were most likely
to be untreated (38.3%).

CONCLUSIONS AND RELEVANCE The findings of this cross-sectional epidemiological analysis

suggest that the increased incidence of stage I NSCLC at diagnosis likely reflected improved
evaluation of incidental nodules. A smaller proportion of patients aged 65 years or older with
stage IV NSCLC were treated. Earlier detection and availability of effective treatments may
underlie increased overall NSCLC prevalence, and higher than previously reported survival.

Author Affiliations: VA Nebraska

Western Iowa Health Care System,
Omaha, Nebraska (Ganti); University
of Nebraska Medical Center, Omaha
(Ganti); AstraZeneca, Gaithersburg,
Maryland (Klein, Cotarla, Seal, Chou).
Corresponding Author: Apar Kishor
Ganti, MD, MS, Division of
Oncology-Hematology, Professor
(Courtesy) of Biochemistry and
Molecular Biology, University of
Nebraska Medical Center, 986840
JAMA Oncol. 2021;7(12):1824-1832. doi:10.1001/jamaoncol.2021.4932 Nebraska Medical Center, Omaha, NE
Published online October 21, 2021. 68198-6840 ([email protected]).

1824 (Reprinted) jamaoncology.com

© 2021 American Medical Association. All rights reserved.

Downloaded from jamanetwork.com by Brenda Rodriguez on 04/16/2024
 Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non–Small Cell Lung Cancer Original Investigation Research

L
ung cancer is the leading cause of cancer-related deaths
in men and women in the US and worldwide.1,2 Non– Key Points
small cell lung cancer (NSCLC) represents approxi-
Question What do the latest US data reveal about non–small cell
mately 84% of all lung cancers, whereas small-cell lung can- lung cancer (NSCLC) epidemiology?
cer (SCLC) represents approximately 13%.1 Historically, NSCLC
Findings In this cross-sectional epidemiological analysis, NSCLC
has had a poor prognosis, particularly in later stages.3 How-
incidence decreased from 2010 to 2017 overall, but rose for
ever, treatment has changed markedly in the past decade with
patients with stage I disease. Prevalence of NSCLC has increased,
wider lung cancer screening, improved radiation techniques, and estimated 5-year survival was 26.4%; a high proportion of
and treatment advances.4,5 These changes have likely re- patients with stage IV disease aged 65 or older years were
sulted in the reported decline in NSCLC mortality.6 Because categorized as not treated.
treatment and prognosis differ by stage, updated epidemio-
Meaning The increased incidence of stage I NSCLC at diagnosis
logical estimates by stage are of interest. likely reflects improved evaluation of incidental nodules;
This cross-sectional epidemiological analysis calculated the availability of more effective treatments may explain increased
most recent estimates of incidence, prevalence, and survival overall prevalence and increased 5-year survival, though patients
in patients with NSCLC, and describes initial treatment over- aged 65 years or older with stage IV NSCLC may be undertreated.
all and by stage in the US.

agnosed with NSCLC in prior years (the earliest year was 2000
when SEER-18 was established). Yearly prevalence for 2010 to
Methods 2016 was estimated based on SEER-18 data and projected to a
Databases national level using the National Cancer Institute’s Projected
The United States Cancer Statistics (USCS) database, and the Prevalence (ProjPrev) software.11
Surveillance, Epidemiology, and End Results (SEER-18) data-
base were used. Detailed descriptions are in eAppendix A in Survival
the Supplement. The analysis was conducted from June to Survival time measures the time, in months, from the date
July 2020. of diagnosis to death. Period survival statistics provide an es-
timate of survival by piecing together the most recent condi-
Study Population tional survival estimates from several cohorts, which are then
Our analysis was based on adults aged 18 years or older who used to generate relative estimates of 1-year, 2-year, 3-year,
were diagnosed with NSCLC starting in 2010 (the first year in 4-year, and 5-year survival rates12,13 (eAppendix A in the
which data were categorized by stage [SEER-18]). NSCLC was Supplement).
identified by International Classification of Diseases for Oncol-
ogy, Third Edition (ICD-O-3) morphology codes (eAppendix B Initial Treatment
in the Supplement).7 The analysis included ICD-O-3 malig- First-course treatment (radiation, chemotherapy, and/or sur-
nant histology/behavior and microscopically confirmed cases. gery) was summarized; other treatments (eg, immuno-
Patient information in these databases is completely deiden- therapy) were not included in the database. Data were sum-
tified and publicly available, hence institutional review board marized in terms of no treatment, single treatment, or multiple
approval was not needed per SEER/National Cancer Institute treatments (various combinations of chemotherapy, radia-
regulations.8,9 tion, and/or surgery).

Study End Points and Statistical Analysis Statistical Software

Lung cancer subtype and histologic distribution were de- Data were analyzed with the SEER*Stat statistical software
scribed. All NSCLC end points were reported for the overall (version 8.3.6.1, April 29, 2020), provided by SEER and SAS
population, as well as by age (<65 or ≥65 years), sex, and stage statistical software (version 9.4, SAS Institute).
at diagnosis.

Incidence
Yearly incidence per 100 000 persons was age-adjusted to the
Results
2000 US standard population.10 The total at-risk populations Database Overview Including Lung Cancer by Type
(denominators) were obtained from the USCS and SEER-18 da- In SEER-NPCR 2010 to 2017, there were over 1.5 million new
tabases. If the overall incidence from 2010 to 2017 was consis- lung cancer cases; of these, approximately 1.28 million were
tent between the SEER-NPCR (national level estimate) and NSCLC (51% male; 70% aged ≥65 years). In SEER-18 over the
SEER-18 databases, the SEER-18 incidence data was considered same period, demographic distributions were similar in the
representative and was projected to a national level by stage. NSCLC population (53% male; 68% aged ≥65 years; median
[Q1-Q3] age at diagnosis was 70 [63-77] years). Overall, NSCLC
Prevalence accounted for most cases (82.9% in SEER-NPCR; 83.9% in
A crude estimate of yearly prevalence per 100 000 persons was SEER-18), followed by SCLC (13.9% in SEER-NPCR; 12.9% in
defined as the yearly incidence plus all patients who were di- SEER-18) (Figure 1, A and B).

jamaoncology.com (Reprinted) JAMA Oncology December 2021 Volume 7, Number 12 1825

© 2021 American Medical Association. All rights reserved.

Downloaded from jamanetwork.com by Brenda Rodriguez on 04/16/2024
 Research Original Investigation Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non–Small Cell Lung Cancer

Figure 1. Distribution of Lung Cancer by Histologic Findings and Distribution of NSCLC by Stage, Age, and Year

A Distribution of lung cancer by histologic findings B Distribution of lung cancer by histologic findings
(SEER-NPCR, 2010-2017 overall) (SEER-18, 2010-2017 overall)

Small cell (n = 215 522) Small cell (n = 47 233)

NSCLC, Squamous cell (n = 376 413) NSCLC, Squamous cell (n = 84 928)
NSCLC, Adenocarcinoma (n = 701 768) NSCLC, Adenocarcinoma (n = 176 091)
NSCLC, Large cell (n = 23 686) NSCLC, Large cell (n = 5432)
NSCLC, NOS (n = 179 870) NSCLC, NOS (n = 41 741)
Carcinoma, NOS (n = 44 768) Carcinoma, NOS (n = 10 788)
Sarcomas (n = 2329) Sarcomas (n = 648)
Other specified types (n = 1266) Other specified types (n = 333)

0 10 20 30 40 50 0 10 20 30 40 50
Cases, % Cases, %

C NSCLC stage by histologic findings, overall and by age (SEER-18, 2017) Stage I Stage II Stage IIIA Stage IIIB Stage IV

100

80

60
Cases, %

40

20

0
All ages Aged <65 y Aged ≥65 y All ages Aged <65 y Aged ≥65 y All ages Aged <65 y Aged ≥65 y All ages Aged <65 y Aged ≥65 y
(n = 10 318) (n = 2510) (n = 7808) (n = 22 611) (n = 7108) (n = 15 503) (n = 497) (n = 195) (n = 302) (n = 4293) (n = 1430) (n = 2863)

Squamous cell Adenocarcinoma Large cell Not otherwise specified

D Distribution of NSCLC stage by year (SEER-18, 2010-2017)

Stage I Stage II Stage IIIA Stage IIIB Stage IV
50

40

30
Cases, %

20

10

0
2010 2011 2012 2013 2014 2015 2016 2017
(n = 35 821) (n = 35 917) (n = 36 363) (n = 36 553) (n = 36 945) (n = 37 360) (n = 37 663) (n = 37 719)

NOS indicates not otherwise specified; NSCLC, non–small cell lung cancer; SEER-18, Surveillance, Epidemiology, and End Results; NPCR, National Program of Cancer
Registries. A, Distribution of lung cancer by histologic findings (SEER-NPCR, 2010-2017 overall). B, Distribution of lung cancer by histologic findings (SEER-18,
2010-2017 overall). C, NSCLC stage by histologic findings, overall and by age (SEER-18, 2017). D, Distribution of NSCLC stage by year (SEER-18, 2010-2017).

NSCLC Histology and Staging (eAppendix C, eTable 1 in the Supplement). The frequency dis-
Adenocarcinoma was the most common histologic finding tribution of NSCLC stages by histologic analysis at initial di-
(54.7%) followed by squamous cell (29.4%) in the SEER- agnosis (SEER-18, 2017) is shown in Figure 1C; the proportion
NPCR database (57.1% and 27.6%, respectively, in SEER-18) of stage I at diagnosis was higher among older patients, whereas

1826 JAMA Oncology December 2021 Volume 7, Number 12 (Reprinted) jamaoncology.com

© 2021 American Medical Association. All rights reserved.

Downloaded from jamanetwork.com by Brenda Rodriguez on 04/16/2024
 Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non–Small Cell Lung Cancer Original Investigation Research

Figure 2. Annual Incidence of NSCLC (2010-2017) Overall and by Age and Stage

A Overall and by age (SEER-NPCR; SEER-18) B Overall by stage (nationwide projection of SEER-18)
300 50

Stage I Stage IIIB

250
Incidence per 100 000 persons

Incidence per 100 000 persons

40 Stage II Stage IV
Stage IIIA
200
30
All ages, SEER-NPCR Aged <65 y, SEER-18
150 All ages, SEER-18 Aged ≥65 y, SEER-NPCR
Aged <65 y, SEER-NPCR Aged ≥65 y, SEER-18
20
100

10
50

0 0
2010 2011 2012 2013 2014 2015 2016 2017 2010 2011 2012 2013 2014 2015 2016 2017
Year Year

C Aged <65 y and by stage (nationwide projection of SEER-18) D Aged ≥65 y and by stage (nationwide projection of SEER-18)

20 120 Stage I Stage IIIA Stage IV

Stage II Stage IIIB
Stage I Stage IIIB
Stage II Stage IV 100
Incidence per 100 000 persons

Incidence per 100 000 persons

16
Stage IIIA
80
12

60

8
40

4
20

0 0
2010 2011 2012 2013 2014 2015 2016 2017 2010 2011 2012 2013 2014 2015 2016 2017
Year Year

NSCLC indicates non–small cell lung cancer; SEER-18, Surveillance, Epidemiology, and End Results; NPCR, National Program of Cancer Registries. A, NSCLC incidence
overall and by age (SEER-NPCR; SEER-18). B, Overall incidence by stage (nationwide projection of SEER-18). C, Incidence among those younger than 65 years by age
and stage (nationwide projection of SEER-18). D, Incidence among those aged 65 years or older by stage (nationwide projection of SEER-18). Maximum values of
vertical axes vary based on range of data shown. Overall incidence data (ie, not broken out by stage) are from SEER-NPCR and SEER-18. All other data are SEER-18
projected to a national level.

the proportion of stage IV was higher among younger pa- In SEER-18, the incidence of NSCLC decreased from 43.6
tients. From 2010 to 2017 (SEER-18), the proportion of stage I to 37.5 per 100 000 from 2010 to 2017 (Figure 2A) (eAppen-
at diagnosis increased from 24% to 29%, whereas the propor- dix C, eTable 2 in the Supplement). The incidence per 100 000
tion of stage IV decreased from 48% to 44.1% (Figure 1D). decreased from 2010 to 2017 in both age strata: for patients
younger than 65 years, incidence decreased from 13.5 to 11.4;
Incidence of NSCLC (SEER-NPCR and SEER-18) for patients aged 65 years or older, incidence decreased from
In SEER-NPCR, the incidence of NSCLC decreased from 46.4 251.8 to 217.9. Of 39 220 incident cases in 2017, 11 641 (30%)
to 40.9 per 100 000 from 2010 to 2017 (Figure 2A) (eAppen- were younger than 65 years, and 27 579 (70%) were aged 65
dix C, eTable 2 in the Supplement). The incidence was mark- years or older. The incidence was higher for men than for
edly higher among older than younger patients and de- women, and decreased from 2010 to 2017 in both sexes: for
creased from 2010 to 2017 in both age groups: for patients men, the incidence decreased from 52.6 to 42.4 per 100 000;
younger than 65 years, the incidence decreased from 15.5 to for women, the incidence decreased from 36.8 to 33.8. The in-
13.5 per 100 000; for patients aged 65 years or older, the inci- cidence and general patterns of incidence were consistent
dence decreased from 259.9 to 230.0. Of 163 716 incident cases between the SEER-NPCR and SEER-18 databases (eAppendix
of NSCLC in 2017, 50 795 (31%) were younger than 65 years, C, eTable 2 in the Supplement).
and 112 921 (69%) were aged 65 years or older. The incidence
of NSCLC was consistently higher for men than for women, and Incidence of NSCLC by Stage (Nationwide Projection
decreased from 2010 to 2017 in both sexes: for men, the inci- of SEER-18)
dence decreased from 56 to 46.5 per 100 000; for women, From 2010 to 2017, the incidence of stage II, IIIA, and IIIB
the incidence per 100 000 decreased from 39.1 to 36.6. NSCLC was stable, and stage IV decreased slightly from 21.7

jamaoncology.com (Reprinted) JAMA Oncology December 2021 Volume 7, Number 12 1827

© 2021 American Medical Association. All rights reserved.

Downloaded from jamanetwork.com by Brenda Rodriguez on 04/16/2024
 Research Original Investigation Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non–Small Cell Lung Cancer

27.9%). For stage IV patients, the 5-year survival estimate was

Figure 3. Annual Prevalence of NSCLC (2010-2016,
Nationwide Projection of SEER-18) Overall and by Age
5.8% (4.6% for age ≥65 years; 7.5% for age <65 years).

1000 Initial Treatment for NSCLC (SEER-18)

In 2016, approximately 23% of all NSCLC patients were cat-
Aged ≥65 y
Prevalence per 100 000 persons

800 egorized as receiving no treatment, almost half (49.5%) re-

ceived a single modality treatment (ie, surgery, chemo-
600 therapy, or radiation), and 27.7% received multiple treatments
initially; this distribution was similar in all years assessed (eAp-
pendix C, eTable 5 in the Supplement). The remainder of this
400
section will primarily focus on 2016 (most recent year with data
All ages available). Of patients who received no treatment, most were
200
aged 65 years or older (77.5%). Receiving no treatment was
Aged <65 y more common in patients aged 65 years or older vs those
0
2010 2011 2012 2013 2014 2015 2016 younger than 65 years (25.4% vs 16.7%), and in patients with
Year stage IV vs stages I to IIIB NSCLC (33.1% vs 11.8%) (eAppendix
C, eTables 5 and 6 in the Supplement). Treatment patterns in
NSCLC indicates non–small cell lung cancer; SEER-18, Surveillance, the overall population were generally consistent for men and
Epidemiology, and End Results. Prevalence data are from SEER-18 projected
to a national level.
women. A higher proportion of older patients (aged ≥65 years)
received initial treatment with a single modality than those
younger than 65 years (51.3% vs 45.6%); whereas a lower
proportion of older than younger patients received multiple
to 19.6 per 100 000, whereas stage I increased from 10.8 to treatments (23.3% vs 37.7%).
13.2 per 100 000 (Figure 2B) (eAppendix C, eTable 3 in the
Supplement). The absolute increase in stage I incidence was Treatment Trends by Stage
more pronounced among patients aged 65 years or older (60.3 Through years 2010 to 2016, notable shifts in initial treat-
to 64.2 per 100 000 vs 3.32 to 3.72 per 100 000 in the aged <65 ment trends were observed in all NSCLC stages except stage
years cohort) though the relative increases in stage I inci- IV. Generally, the proportions of patients with stages I to IIIA
dence were greater among patients younger than 65 years receiving surgery alone as initial therapy decreased, whereas
(12% vs 6.6% for those aged ≥65 years, Figure 2, C and D; eAp- the proportions with stages I to II receiving radiation alone as
pendix C, eTable 3 in the Supplement). The greatest absolute initial therapy increased; the proportion of patients with stage
and relative reductions in incidence from 2010 to 2017 were IIIB disease receiving radiation alone decreased (eAppendix
observed among patients aged 65 years or older with stage IV C, eTable 6 in the Supplement). Among patients with stage I
NSCLC (108.6 to 85.5 per 100 000, a change of −27%) com- disease, the increase in single treatment radiation from 2010
pared with the younger than 65 years cohort (8.7 to 7.4 per to 2016 was more pronounced in patients aged 65 years or
100 000, a change of −17.6%). older (17.4% to 30.2%) than those younger than 65 years (7.7%
to 12.8%).
Prevalence of NSCLC (Nationwide Projection of SEER-18) The approximate proportions of patients with stage IV
The prevalence of NSCLC increased from 175.3 to 198.3 per disease receiving no treatment, single treatment, and mul-
100 000 persons from 2010 to 2016 (Figure 3) (eAppendix C, tiple treatments were 31% to 33%, 40% to 41%, and 26% to
eTable 4 in the Supplement). This trend was observed in both 28%, respectively, without notable variation through the
men and women over the same time frame; women had a years. A higher proportion of patients with stage IV disease
higher prevalence than men in each year assessed (eg, in 2016: aged 65 years or older received no treatment compared with
185.8 per 100 000 persons for men vs 210.3 per 100 000 those younger than 65 years (38.3% vs 22.8%), whereas a
persons for women). Whereas prevalence from 2010 to 2016 lower proportion received multiple treatment modalities as
generally rose among patients younger than 65 years, it de- their first line of treatment than those younger than 65 years
creased among those aged 65 years or older. The prevalence (20.8% vs 37.3%). The proportions of patients with stage IV
in patients aged 65 years or older was consistently 9 times disease receiving single treatments, and trends in the dis-
higher than that in patients younger than 65 years (eg, in 2016: tribution of single treatments, were comparable between
812.4 vs 87.9 per 100 000 persons) (Figure 3). age groups.
Treatment trends by age and stage in 2016 are summa-
Survival After Diagnosis of NSCLC (SEER-18) rized in Figure 4. The proportion of patients categorized as hav-
Estimates of survival based on SEER-18 are summarized in the ing no treatment increased with increasing stage: 8%, 12.2%,
Table. The 1-year survival for patients with NSCLC was 55.1% 16.8%, 18.5%, and 33.1% of patients in stages I, II, IIIA, IIIB, and
whereas the 5-year survival was 26.4%. Period survival esti- IV, respectively (Figure 4A). Regardless of stage, a greater pro-
mates were lower for men vs women (5-year estimate: 21.9% portion of patients aged 65 years or older received no initial
vs 31.3%), and slightly lower for patients aged 65 years or older treatment compared with those younger than 65 years
vs those younger than 65 years (5-year estimate: 25.5% vs (Figure 4, B and C).

1828 JAMA Oncology December 2021 Volume 7, Number 12 (Reprinted) jamaoncology.com

© 2021 American Medical Association. All rights reserved.

Downloaded from jamanetwork.com by Brenda Rodriguez on 04/16/2024
 Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non–Small Cell Lung Cancer Original Investigation Research

Table. Period Survival (SEER-18)

Period survival rate, %

Characteristic 1-year 2-year 3-year 4-year 5-year
Overall 55.1 41.0 33.8 29.5 26.4
Age, y
<65 57.7 42.7 35.2 30.8 27.9
≥65 53.7 40.1 33.1 28.8 25.5
Men 50.4 35.6 28.6 24.6 21.9
Women 60.3 46.9 39.5 34.8 31.3
Stage
I 92.8 85.2 78.2 73.1 68.4
II 78.7 64.3 55.3 49.2 45.1
IIIA 66.5 47.3 37.2 30.6 26.2
IIIB 54.3 34.3 25.4 20.5 17.3
IV 31.3 16.6 10.6 7.5 5.8
Age <65 y
Stage
I 94.6 88.9 83.2 78.7 74.9
II 86.7 73.5 64.9 59.0 55.3
IIIA 73.5 54.4 43.7 37.0 32.0
IIIB 59.2 37.8 28.9 23.5 20.4
IV 36.5 20.2 13.1 9.6 7.5
Age ≥65 y
Stage
I 92.0 83.6 76.0 70.6 65.3
II 75.1 60.2 50.9 44.7 40.0
IIIA 62.8 43.4 33.7 27.1 22.9
IIIB 51.0 31.9 23.0 18.2 15.1
Abbreviation: SEER, Surveillance,
IV 28.0 14.3 9.0 6.2 4.6
Epidemiology, and End Results.

This interpretation is supported by comparing changes in

Discussion incidence for each stage among patients aged 65 years or older
with the percentage of Medicare Part B patients receiving
Overall, in this study, the incidence of NSCLC decreased slightly low-dose CT scans for lung cancer screening (HCPCS code
from 2010 to 2017; however, when examined by stage, the in- G0297). Figure 2B shows that the incidence of stage I NSCLC
cidence of patients initially diagnosed with stage IV disease in this population was relatively flat until 2015, at which point
decreased, whereas that of stage I NSCLC increased. The in- it began to increase. The first column of eAppendix C and
cidence of stages II to III was relatively stable. One possible ex- eTable 7 in the Supplement provides detail behind Figure 2B,
planation for the increase in patients diagnosed with stage I showing the year-to-year percentage changes in stage I NSCLC
NSCLC may be the increase in screening after publication of incidence from 2010 to 2017 (calculated using the results in
the National Lung Screening Trial (NSLT) in 2011 and US eTable 3 in the Supplement). Columns 2 to 4 of eTable 7 in the
Preventive Services Task Force in 2013.14,15 Although the CMS Supplement are the number of Medicare Part B patients re-
National Coverage Decision was implemented in 2015, it is ceiving low-dose CT scans for lung cancer screening, the total
possible that awareness of the benefits of lung cancer screen- number of Medicare Part B patients, and the percent receiv-
ing after the publication of the NLST results in 2011 may have ing low-dose CT scans for lung cancer screening. There were
led to better follow-up of patients identified as having inci- no CT scans from 2010 to 2014 since funding for them started
dental pulmonary nodules and therefore diagnosed with lung in 2015.16 Year-on-year stage I incidence increased by 1.99%,
cancer at an earlier stage. However, our data, though support- 2.03%, and 3.03% from 2015 to 2017, coincident with in-
ive, cannot completely attribute the stage shift to better creases in the percent of Medicare Part B patients receiving
follow-up of patients with these incidental pulmonary find- CT scans.
ings, given the overall limited uptake of lung cancer screen- The incidence of NSCLC decreased across sex and age
ing to date. Among patients aged 65 years or older, an in- subgroups. These findings are consistent with a prior SEER-
crease in stage I NSCLC accompanied by a decrease in stage based comprehensive overview17 of lung cancer over the past
IV NSCLC at diagnosis is most likely associated with in- 4 decades, which reported decreases in lung cancer inci-
creased screening in this age group, and should be used to pro- dence among both men and women in the past decade, and
mote the establishment of lung cancer screening programs. largely attributed these trends to tobacco control programs.

jamaoncology.com (Reprinted) JAMA Oncology December 2021 Volume 7, Number 12 1829

© 2021 American Medical Association. All rights reserved.

Downloaded from jamanetwork.com by Brenda Rodriguez on 04/16/2024
 Research Original Investigation Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non–Small Cell Lung Cancer

Figure 4. Distribution of Initial Treatment by NSCLC Stage (SEER-18, 2016)

A Treatment distribution of all ages by stage

80 No treatment Single treatment, radiation

Single treatment, surgery Chemotherapy and radiation
Single treatment, chemotherapy Multiple treatments (other)

60
Cases, %

40

20

0
Stage I Stage II Stage IIIA Stage IIIB Stage IV
(n = 10 306) (n = 3238) (n = 4806) (n = 2115) (n = 16 890)

B Treatment distribution of those aged <65 y by stage

80

60
Cases, %

40

20

0
Stage I Stage II Stage IIIA Stage IIIB Stage IV
(n = 2665) (n = 885) (n = 1474) (n = 761) (n = 5753)

C Treatment distribution of those aged ≥65 y by stage

80

60
Cases, %

40
NSCLC indicates non–small cell lung
cancer; SEER-18, Surveillance,
Epidemiology, and End Results.
20
A, for all ages; B, for those younger
than 65 years; and C, those aged 65
years or older. Multiple treatments
(other) indicates various
0
Stage I Stage II Stage IIIA Stage IIIB Stage IV combinations of chemotherapy,
(n = 7641) (n = 2353) (n = 3332) (n = 1354) (n = 11 137) radiation, and/or surgery (excluding
chemotherapy + radiation).

The decrease in NSCLC incidence among women was smaller The 5-year period survival estimate for the NSCLC popu-
than that in men; this is consistent with a North American lation was 26.4%—higher than previously published period es-
Association of Central Cancer Registries (NAACCR)-based timates of 23.3% (2014)19 and 24.6% (2015).20 This increase is
report18 in which lung cancer incidence decreased in both men consistent with a trend of increasing 5-year survival in a SEER-
and women from 1995–2015, but the magnitude of decrease based analysis of lung cancer, and can be explained by im-
was greater in men. provements in treatment and/or earlier treatment associated

1830 JAMA Oncology December 2021 Volume 7, Number 12 (Reprinted) jamaoncology.com

© 2021 American Medical Association. All rights reserved.

Downloaded from jamanetwork.com by Brenda Rodriguez on 04/16/2024
 Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non–Small Cell Lung Cancer Original Investigation Research

with earlier diagnosis, though the possibility of lead time bias ment modalities based on age, and treatments should not be
(longer recorded survival postcancer diagnosis resulting excluded simply based on age26; thus, this relative undertreat-
from earlier detection of cancer) cannot be completely ment of older adults needs further investigation. Reasons for
excluded.17,21,22 The 5-year survival estimate was lowest for pa- not treating older patients may include comorbid conditions
tients with stage IV NSCLC, especially among those aged 65 that preclude aggressive therapy, reluctance of older patients
years or older (4.6%), but still higher than previously reported.3 to receive treatments, and therapeutic nihilism on the part
Period survival estimates were lower for men than women, of the practitioner.27 Of note, immunotherapy for NSCLC
and only slightly lower for older than for younger patients. was not available as a first-line option prior to November 2016,
In contrast to the overall decline in incidence, but consis- and thus would not affect the most recently released registry
tent with the improvement in survival, the overall preva- data that form the basis of our report. Future estimates
lence of NSCLC increased from 2010 to 2016, suggesting that may reflect the improved survival seen in clinical trials with
patients are generally living longer after diagnosis. Whereas immunotherapy agents.
NSCLC prevalence increased among younger patients, it de-
creased among those aged 65 years or older. The overall preva- Limitations
lence trend was driven by the majority of the US population Limitations of this analysis include its retrospective nature and
being younger (ie, the US population [denominator] was mostly use of registries that do not necessarily classify treatments as
aged <65 years), although older patients represented ap- clinicians do. Also, due to natural lag in cancer registry data
proximately two-thirds of NSCLC patients (ie, NSCLC cases collection/release, certain data in the SEER-18 registry were
[numerator] were mostly aged ≥65 years; eAppendix C, eTable 4 only available through 2016. Another potential limitation is that
in the Supplement). the SEER-18 database does not include a nationwide sample.
Although surgery remains the predominant initial treat- These limitations notwithstanding, the SEER-NPCR data-
ment for stage I NSCLC, there has been a rise in the use of ra- base offered the advantage of directly providing nationally
diation over the past decade. This is likely due to increasing representative incidence data. After establishing consistency
data on the efficacy of stereotactic body radiation in early- between SEER-NPCR and SEER-18 in terms of NSCLC inci-
stage NSCLC.23,24 Despite availability of more effective treat- dence, we projected the more detailed prevalence and inci-
ments for NSCLC, a substantial proportion of patients (ap- dence information with staging data available in SEER-18 to a
proximately 23% in 2016) may be undertreated. This potentially national level. Thus, our report provides an important and com-
undertreated proportion was higher among patients aged 65 prehensive update of epidemiologic information for NSCLC.
years or older vs those younger than 65 years (25.4% vs 16.7%)
and could be a factor underlying the decreased NSCLC preva-
lence in the older subgroup. Patients with stage IV NSCLC aged
65 years or older had the highest proportion with no treatment.
Conclusions
Although concerning, these findings are not surprising, as pre- In this study, the incidence of NSCLC decreased from 2010 to
vious studies in early-stage disease have shown that older in- 2017, and across age and sex subgroups. A rise in the inci-
dividuals are not offered adjuvant chemotherapy after surgi- dence of stage I NSCLC at diagnosis likely reflects increased
cal resection, even though the magnitude of benefit with such screening in the past decade. Increased overall prevalence of
treatment was the same as in younger adults.25 However, these NSCLC and higher 5-year survival than reported previously may
data should be interpreted with caution since the SEER-18 da- be associated with earlier detection of NSCLC and introduc-
tabase only includes first-course radiation, chemotherapy, and tion of more effective treatments. Despite availability of ef-
surgery but not other treatments (eg, immunotherapy). Thus, fective treatments, patients aged 65 years or older with stage
some of the patients categorized as having no treatment may IV NSCLC have the lowest 5-year survival, which may be at least
have received other treatments not included in the database. partly due to undertreatment. The reasons for this should be
However, the guidelines do not differentiate between treat- studied further.

ARTICLE INFORMATION Administrative,technical,ormaterialsupport:Klein,Seal. Role of the Funder/Sponsor: AstraZeneca

Accepted for Publication: July 20, 2021. Supervision: Ganti, Klein, Cotarla, Seal. contributed to the design and conduct of the study;
Conflict of Interest Disclosures: Dr Ganti is a collection, management, analysis, and
Published Online: October 21, 2021. interpretation of the data; preparation, review, and
doi:10.1001/jamaoncol.2021.4932 consultant for AstraZeneca, Genentech, and
Flagship Biosciences, has served on advisory approval of the manuscript; and the decision to
Author Contributions: Drs Ganti and Seal had full boards for AstraZeneca, Blueprint Medicines, Jazz submit the manuscript for publication.
access to all of the data in the study and take Pharmaceuticals, Cardinal Health, Mirati Data Sharing Statement: Data underlying the
responsibility for the integrity of the data and the Therapeutics, and G1 Therapeutics, and receives findings described in this article may be obtained in
accuracy of the data analysis. research support from Takeda and Oncoceutics. accordance with AstraZeneca’s data sharing policy
Concept and design: Ganti, Cotarla, Seal, Chou. Ms Klein, Dr Seal, and Ms Chou are former described at: https://astrazenecagrouptrials.
Acquisition, analysis, or interpretation of data: Klein, employees of AstraZeneca and were employees of pharmacm.com/ST/Submission/Disclosure.
Cotarla, Seal, Chou. and shareholders in AstraZeneca at the time of the
Drafting of the manuscript: Ganti, Klein, Seal, Chou. Additional Contributions: We thank Lance
study. Dr Cotarla is an employee of and shareholder Brannman, PhD, for his contributions to initiating
Critical revision of the manuscript for important in AstraZeneca.
intellectual content: All authors. the study and interpreting the data. Medical writing
Statistical analysis: Chou. Funding/Support: This study was funded by support was provided by Kulvinder Singh, PharmD,
Obtained funding: Seal. AstraZeneca. of KK Singh, LLC (Branchburg, New Jersey) and

jamaoncology.com (Reprinted) JAMA Oncology December 2021 Volume 7, Number 12 1831

© 2021 American Medical Association. All rights reserved.

Downloaded from jamanetwork.com by Brenda Rodriguez on 04/16/2024
 Research Original Investigation Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non–Small Cell Lung Cancer

medical editing support was provided by Susanne cdc.gov/cancer/uscs/public-use/pdf/uscs-public- 18. Jemal A, Miller KD, Ma J, et al. Higher lung
Gilbert, MA, of Ashfield MedComms (New York, use-database-fact-sheet-508.pdf cancer incidence in young women than young men
New York). Both were in accordance with Good 9. National Cancer Institute SEER-Medicare linked in the United States. N Engl J Med. 2018;378(21):
Publication Practice (GPP3) guidelines and were database—IRB approval & HIPAA regulations. 1999-2009. doi:10.1056/NEJMoa1715907
funded by AstraZeneca. Accessed Sept 30, 2021. https://healthcaredelivery. 19. Noone AM, Howlader N, Krapcho M, et al, eds.
cancer.gov/seermedicare/privacy/hipaa.html SEER Cancer Statistics Review, 1975–2015, National
REFERENCES Cancer Institute. Bethesda, MD. Based on
10. National Cancer Institute. Surveillance,
1. American Cancer Society. Facts & Figures 2019. Epidemiology, and End Results Program. Standard November 2017 SEER data submission, posted to
Accessed June 13, 2020. https://www.cancer.org/ Population – 19 Age Groups. Accessed July 18, the SEER web site, April 2018. Accessed September
content/dam/cancer-org/research/cancer-facts- 2020. https://seer.cancer.gov/stdpopulations/ 21, 2021. https://seer.cancer.gov/csr/1975_2015/
and-statistics/annual-cancer-facts-and-figures/ stdpop.19ages.html 20. Howlader N, Noone AM, Krapcho M, et al SEER
2019/cancer-facts-and-figures-2019.pdf Cancer Statistics Review, 1975–2016, National
11. National Cancer Institute. Surveillance Research
2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Program. Projected Prevalence (ProjPrev) software. Cancer Institute. Bethesda, MD. Based on
Torre LA, Jemal A. Global cancer statistics 2018: Accessed June 21, 2021. https://surveillance.cancer. November 2018 SEER data submission, posted to
GLOBOCAN estimates of incidence and mortality gov/projprev/ the SEER web site, April 2019. Accessed September
worldwide for 36 cancers in 185 countries. CA 21, 2021. https://seer.cancer.gov/csr/1975_2016/
Cancer J Clin. 2018;68(6):394-424. doi:10.3322/ 12. Brenner H, Hakulinen T. Advanced detection of
time trends in long-term cancer patient survival: 21. Finks JF, Osborne NH, Birkmeyer JD. Trends in
caac.21492 hospital volume and operative mortality for
experience from 50 years of cancer registration in
3. Cetin K, Ettinger DS, Hei YJ, O’Malley CD. Finland. Am J Epidemiol. 2002;156(6):566-577. high-risk surgery. N Engl J Med. 2011;364(22):
Survival by histologic subtype in stage IV nonsmall doi:10.1093/aje/kwf071 2128-2137. doi:10.1056/NEJMsa1010705
cell lung cancer based on data from the 22. Andersson TM-L, Rutherford MJ, Humphreys K.
Surveillance, Epidemiology and End Results 13. National Cancer Institute. Division of Cancer
Control and Population Sciences. Surveillance Assessment of lead-time bias in estimates of
Program. Clin Epidemiol. 2011;3:139-148. doi:10. relative survival for breast cancer. Cancer Epidemiol.
2147/CLEP.S17191 Research Program. Accessed June 21, 2021. https://
surveillance.cancer.gov/survival/cohort.html 2017;46:50-56. doi:10.1016/j.canep.2016.12.004
4. Diwanji TP, Mohindra P, Vyfhuis M, et al. 23. Timmerman RD, Paulus R, Pass HI, et al.
Advances in radiotherapy techniques and delivery 14. Aberle DR, Adams AM, Berg CD, et al; National
Lung Screening Trial Research Team. Reduced Stereotactic body radiation therapy for operable
for non-small cell lung cancer: benefits of early-stage lung cancer: findings from the NRG
intensity-modulated radiation therapy, proton lung-cancer mortality with low-dose computed
tomographic screening. N Engl J Med. 2011;365(5): Oncology RTOG 0618 Trial. JAMA Oncol. 2018;4(9):
therapy, and stereotactic body radiation therapy. 1263-1266. doi:10.1001/jamaoncol.2018.1251
Transl Lung Cancer Res. 2017;6(2):131-147. doi:10. 395-409. doi:10.1056/NEJMoa1102873
21037/tlcr.2017.04.04 15. Screening for Lung Cancer. U.S. Preventive 24. Abel S, Hasan S, Horne ZD, Colonias A,
Services Task Force Final Recommendation. Wegner RE. Stereotactic body radiation therapy in
5. Jones GS, Baldwin DR. Recent advances in the early-stage NSCLC: historical review, contemporary
management of lung cancer. Clin Med (Lond). 2018; December, 2013. Accessed September 21, 2021.
www.uspreventiveservicestaskforce.org/home/ evidence and future implications. Lung Cancer
18(suppl 2):s41-s46. doi:10.7861/clinmedicine.18-2-s41 Manag. 2019;8(1):LMT09. doi:10.2217/lmt-2018-0013
getfilebytoken/KsRfT_uSd7J6WeXmbvbkav
6. Howlader N, Forjaz G, Mooradian MJ, et al. 25. Ganti AK, Williams CD, Gajra A, Kelley MJ. Effect
The effect of advances in lung-cancer treatment on 16. Centers for Medicare and Medicaid Services.
Medicare Coverage of Screening for Lung Cancer of age on the efficacy of adjuvant chemotherapy for
population mortality. N Engl J Med. 2020;383(7): resected non-small cell lung cancer. Cancer. 2015;
640-649. doi:10.1056/NEJMoa1916623 with Low Dose Computed Tomography (LDCT).
MLN Matters Number: MM9246. October 15, 2015. 121(15):2578-2585. doi:10.1002/cncr.29360
7. Fritz A, Percy C, Jack A, et al, eds. International Accessed September 21, 2021. www. 26. Ganti AK, deShazo M, Weir AB III, Hurria A.
Classification of Diseases for Oncology. 3rd edition. lungcancerscreeningguide.org/wp-content/ Treatment of non-small cell lung cancer in the older
Geneva, Switzerland: World Health Organization; uploads/2018/10/MLM- patient. J Natl Compr Canc Netw. 2012;10(2):230-239.
2000. Accessed September 25, 2020. https://apps. MattersMedicareCoverageof-Screening.-pdf.pdf doi:10.6004/jnccn.2012.0021
who.int/iris/bitstream/handle/10665/96612/
9789241548496_eng.pdf;jsessionid= 17. Lu T, Yang X, Huang Y, et al. Trends in the 27. Blanco R, Maestu I, de la Torre MG, Cassinello A,
9F6F5CB6C762D10A185888244FDA8B18? incidence, treatment, and survival of patients with Nuñez I. A review of the management of elderly
sequence=1 lung cancer in the last four decades. Cancer Manag patients with non-small-cell lung cancer. Ann Oncol.
Res. 2019;11:943-953. doi:10.2147/CMAR.S187317 2015;26(3):451-463. doi:10.1093/annonc/mdu268
8. NPCR and SEER – US Cancer statistics public use
database. Accessed June 8, 2020. https://www.

1832 JAMA Oncology December 2021 Volume 7, Number 12 (Reprinted) jamaoncology.com

© 2021 American Medical Association. All rights reserved.

Downloaded from jamanetwork.com by Brenda Rodriguez on 04/16/2024