The impact of age on survival in stage II colon cancer: a SEER database analysis stratified by chemotherapy status
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Introduction
Colorectal carcinoma ranks as the third most prevalent malignant neoplasm and the second leading cause of cancer-related mortality on a global scale (1,2). The current clinical management and prognostic assessment of colon cancer are predominantly predicated on the TNM (tumor-lymph node-metastasis) classification system. However, the prognostic stratification provided by TNM staging is often deemed imprecise and lacks personalized applicability, yielding suboptimal predictive accuracy (3-5). This limitation is particularly pronounced in the context of stage II colon cancer, which exhibits significant heterogeneity and encompasses a diverse patient population with varying risks of recurrence and metastasis (6,7). Despite being classified as an early-stage disease, stage II colon cancer accounts for approximately 16% of colon cancer-related fatalities. The 5-year overall survival rates for this stage range from 84% for T3N0 to 67% for T4bN0 (8). The administration of chemotherapy for stage II colon cancer remains a contentious issue (9-11). The clinical management of stage II colon cancer is further complicated by the disease’s heterogeneity and the variability in patient responses to therapeutic interventions. Patient age is a pivotal factor influencing treatment decisions and prognostic estimations. The multifaceted influence of age on the prognosis of stage II colon cancer necessitates further investigation to enhance clinical guidance.
Age is a substantial determinant of colon cancer prognosis (12,13). The prognostic implications of age in stage II colon cancer, however, remain a subject of debate. Younger colon cancer patients, typically defined as those under 40 years of age, are often perceived to have a poorer prognosis, attributed to the assumption that tumors in this demographic may exhibit increased aggressiveness, reduced treatment responsiveness, and a heightened propensity for lymph node metastasis and recurrence (14,15). Conversely, elderly patients may present with a higher burden of chronic diseases and comorbidities, which can adversely affect their capacity to tolerate and respond to treatment (13). They may also be more inclined to opt for conservative treatment options due to concerns regarding potential side effects, thereby potentially impacting treatment outcomes (16,17). This dichotomy partly elucidates the observed trend of younger patients being more likely to receive chemotherapy, while older patients are more likely to decline it due to fear of its adverse effects.
A comprehensive analysis of clinical and pathological characteristics, alongside survival outcomes, is imperative to elucidate the impact of age on the prognosis of stage II colon cancer patients. The Surveillance, Epidemiology, and End Results (SEER) program offers an invaluable dataset for such analyses. By leveraging SEER data, it becomes feasible to assess the influence of age on clinicopathological features and survival in this patient cohort. We present this article in accordance with the STROBE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2026-1-0088/rc).
Methods
Patients
This study analyzed data from seventeen U.S. cancer registries, representing a substantial portion of the population (18). Patient selection was based on a diagnosis of stage II colon cancer between 2000 and 2020, consistent with the American Joint Committee on Cancer (AJCC) Staging Manual (7th Edition). We utilized the SEER*Stat software (v8.4.3) for data extraction and management, ensuring process efficiency. The analysis excluded patients with unspecified age or additional malignancies. The institutional review board of the authors’ affiliation granted ethical approval for this study.
To evaluate the prognostic impact of age, patients were stratified into six groups: <40, 40–49, 50–59, 60–69, 70–79, and >80 years, with the <40-year group as the reference. Race was categorized per the SEER recode system as White, Black, American Indian/Alaska Native, and Asian or Pacific Islander. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
Statistical analysis
Clinicopathological characteristics across age groups were analyzed using the Chi-squared test. Overall survival was estimated using the Kaplan-Meier method, and differences in survival distributions were assessed using the log-rank test. Both univariate and multivariate Cox proportional hazards models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality.
To assess the potential interaction between age and chemotherapy status, we included age group, chemotherapy status (yes/no), and their product term (age × chemotherapy) in the Cox regression model. The overall significance of the interaction terms was evaluated using the Wald test. If the overall P value for the interaction was <0.05, age effects were further reported stratified by chemotherapy; otherwise, the interaction was considered non-significant, and the main-effects model was reported.
Results
The association of age with demographic and clinicopathological characteristics in stage II colon cancer
A total of 24,043 individuals diagnosed with stage II colon cancer between 2000 and 2020 were extracted from the SEER database. This cohort included 11,568 (48.1%) males and 12,475 (51.9%) females. Table 1 delineates the demographic, clinicopathological, and therapeutic characteristics of these patients, stratified by age at diagnosis. The age distribution was as follows: <40 years: 658 (2.7%); 40–49 years: 1,784 (7.4%); 50–59 years: 4,145 (17.2%); 60–69 years: 5,542 (23.1%); 70–79 years: 5,714 (23.8%); and ≥80 years: 6,200 (25.8%).
Table 1
| Age at diagnosis | <40 (N=658) | 40–49 (N=1,784) | 50–59 (N=4,145) | 60–69 (N=5,542) | 70–79 (N=5,714) | ≥80 (N=6,200) | P |
|---|---|---|---|---|---|---|---|
| Gender | <0.001 | ||||||
| Female | 306 (46.50) | 831 (46.60) | 1,833 (44.20) | 2,613 (47.10) | 2,957 (51.80) | 3,935 (63.50) | |
| Male | 352 (53.50) | 953 (53.40) | 2,312 (55.80) | 2,929 (52.90) | 2,757 (48.20) | 2,265 (36.50) | |
| Race | <0.001 | ||||||
| White | 490 (74.50) | 1,309 (73.40) | 3,117 (75.20) | 4,296 (77.50) | 4,681 (81.90) | 5,330 (86.00) | |
| Black | 91 (13.80) | 273 (15.30) | 627 (15.10) | 690 (12.50) | 527 (9.20) | 374 (6.00) | |
| Asian or Pacific Islander | 62 (9.40) | 170 (9.50) | 327 (7.90) | 484 (8.70) | 431 (7.50) | 453 (7.30) | |
| American Indian/Alaska Native | 11 (1.70) | 21 (1.20) | 52 (1.30) | 50 (0.90) | 54 (0.90) | 29 (0.50) | |
| Unknown | 4 (0.60) | 11 (0.60) | 22 (0.50) | 22 (0.40) | 21 (0.40) | 14 (0.20) | |
| Grade | <0.001 | ||||||
| I | 73 (11.10) | 155 (8.70) | 355 (8.60) | 458 (8.30) | 423 (7.40) | 405 (6.50) | |
| II | 424 (64.40) | 1,294 (72.50) | 3,037 (73.30) | 4,115 (74.30) | 4,139 (72.40) | 4,235 (68.30) | |
| III | 98 (14.90) | 202 (11.30) | 478 (11.50) | 685 (12.40) | 830 (14.50) | 1,152 (18.60) | |
| IV | 33 (5.00) | 55 (3.10) | 98 (2.40) | 133 (2.40) | 173 (3.00) | 224 (3.60) | |
| Unknown | 30 (4.60) | 78 (4.40) | 177 (4.30) | 151 (2.70) | 149 (2.60) | 184 (3.00) | |
| Chemotherapy | <0.001 | ||||||
| Yes | 275 (41.80) | 668 (37.40) | 1,226 (29.60) | 1,142 (20.60) | 651 (11.40) | 165 (2.70) | |
| No/unknown | 383 (58.20) | 1,116 (62.60) | 2,919 (70.40) | 4,400 (79.40) | 5,063 (88.60) | 6,035 (97.30) | |
| Radiotherapy | <0.001 | ||||||
| Yes | 19 (2.90) | 55 (3.10) | 106 (2.60) | 109 (2.00) | 75 (1.30) | 41 (0.70) | |
| No/unknown | 639 (97.10) | 1,729 (96.90) | 4,039 (97.40) | 5,433 (98.00) | 5,639 (98.70) | 6,159 (99.30) | |
| Surgery | <0.001 | ||||||
| Yes | 653 (99.20) | 1,768 (99.10) | 4,096 (98.80) | 5,467 (98.60) | 5,637 (98.70) | 6,030 (97.30) | |
| No/unknown | 5 (0.80) | 16 (0.90) | 49 (1.20) | 75 (1.40) | 77 (1.30) | 170 (2.70) | |
| T stage | <0.001 | ||||||
| T3 | 502 (76.30) | 1,438 (80.60) | 3,334 (80.40) | 4,576 (82.60) | 4,697 (82.20) | 5,116 (82.50) | |
| T4 | 156 (23.70) | 346 (19.40) | 811 (19.60) | 966 (17.40) | 1,017 (17.80) | 1,084 (17.50) |
Data are presented as number (%). T, tumor.
Marked variations in age-specific incidence rates were observed according to gender and race. Incidence rates increased with age in females but decreased in males. Among racial groups, an increasing trend with age was evident in White patients, contrasting with a declining trend among Black patients.
The administration of chemotherapy demonstrated a pronounced inverse correlation with age. The chemotherapy rate was 41.8% in patients under 40 but only 2.7% in those over 80. Furthermore, the prevalence of grade I tumors declined with age. In contrast, the oldest patients (≥80 years) exhibited the highest frequency of grade II tumors. Rates of surgical intervention and radiotherapy were marginally higher in younger patients. The under-40 age group also had a substantially higher proportion of T4 staging.
Influence of age on prognosis in patients with stage II colon cancer
The analysis indicated a significant inverse relationship between age and overall survival. Patients under 40 had the most favorable prognosis, while those over 80 had the least favorable. The survival curves demonstrate that patients under 40 years of age have the highest survival probability (curve positioned at the top), whereas patients over 80 years of age have the lowest (curve positioned at the bottom, log-rank P<0.001, Figure 1). In a multivariate Cox model adjusted for marital status, sex, and race, the HR for mortality increased progressively with age compared to the under-40 reference group: 1.88 (50–59 years), 2.79 (60–69 years), 4.96 (70–79 years), and 6.46 (≥80 years; 95% CI: 4.35–9.60). Subsequent adjustment for additional covariates, including tumor stage, histologic grade, and treatments, did not attenuate this association (Table 2).
Table 2
| Age at diagnosis (years) | No. of patients | Number of deaths | HR (95% CI)† | HR (95% CI)‡ | HR (95% CI)§ |
|---|---|---|---|---|---|
| <40 | 658 | 71 (10.8) | Reference | Reference | Reference |
| 40–49 | 1,784 | 244 (13.7) | 1.28 (0.98–1.67) | 1.32 (1.01–1.72) | 1.27 (0.98–1.66) |
| 50–59 | 4,145 | 824 (19.9) | 1.88 (1.48–2.40) | 1.96 (1.53–2.50) | 1.87 (1.47–2.39) |
| 60–69 | 5,542 | 1,555 (28.1) | 2.79 (2.19–3.54) | 2.98 (2.34–3.78) | 2.80 (2.21–3.56) |
| 70–79 | 5,714 | 2,567 (44.9) | 4.96 (3.91–6.29) | 5.28 (4.16–6.69) | 4.89 (4.16–6.69) |
| ≥80 | 6,200 | 4,486 (72.4) | 10.2 (8.03–12.9) | 10.9 (8.64–13.87) | 10.95 (8.64–13.9) |
Data are presented as number (%). †, adjusted for race, gender, and marital status. ‡, adjusted for demographic factors (race, gender, marital status) and clinical characteristics (tumor stage, histological grade). §, adjusted for demographic factors (race, gender, marital status), tumor characteristics (stage, histological grade), and treatments received (surgery, chemotherapy, radiotherapy). CI, confidence interval; HR, hazard ratio.
Prognostic disparity by age in stage II colon cancer patients: chemotherapy stratification analysis
We stratified patients with stage II colon cancer by chemotherapy administration to assess the age-dependent prognostic disparity. The Kaplan-Meier curves demonstrate that for patients receiving chemotherapy, the <40 group had the highest survival and the >80 group the lowest (log-rank P<0.001, Figure 2A). The same trend was seen in the no-chemotherapy group (log-rank P<0.001, Figure 2B). After adjusting for sociodemographic, clinicopathological, and treatment variables, mortality risk increased progressively with age in both cohorts. In the chemotherapy group, compared to patients under 40, the HRs were 1.76 (50–59 years), 2.55 (60–69 years), 4.02 (70–79 years), and 6.47 (≥80 years). A similar trend was observed in the non-chemotherapy group, with HRs rising more sharply to 1.98 (50–59 years), 3.05 (60–69 years), 5.44 (70–79 years), and 11.03 (≥80 years). No significant difference was found between the under-40 and 40–49 age groups (Table 3). The interaction test showed that the overall interaction term between age and chemotherapy status was not statistically significant (Wald χ2=7.64, df =5, P=0.18), indicating that the effect of age on survival did not differ significantly across chemotherapy subgroups.
Table 3
| Age at diagnosis (years) | No. of patients | Number of deaths | HR (95% CI)† |
|---|---|---|---|
| With chemotherapy | |||
| <40 | 318 | 50 (15.7) | Reference |
| 40–49 | 795 | 143 (18.0) | 1.34 (0.91–1.98) |
| 50–59 | 1,546 | 365 (23.6) | 1.76 (1.23–2.53) |
| 60–69 | 1,692 | 541 (32.0) | 2.55 (1.79–3.65) |
| 70–79 | 1,045 | 507 (48.5) | 4.02 (2.81–5.77) |
| ≥80 | 273 | 203 (74.4) | 6.47 (4.37–9.59) |
| Without chemotherapy | |||
| <40 | 447 | 53 (11.9) | Reference |
| 40–49 | 1,370 | 204 (14.9) | 1.24 (0.86–1.79) |
| 50–59 | 3,816 | 836 (21.9) | 1.98 (1.42–2.77) |
| 60–69 | 6,469 | 2,039 (31.5) | 3.05 (2.20–4.23) |
| 70–79 | 8,340 | 4,101 (49.2) | 5.44 (3.93–7.53) |
| ≥80 | 10,125 | 7,457 (73.6) | 11.0 (7.98–15.3) |
Data are presented as number (%). †, adjusted for demographic factors (race, gender, marital status), clinical characteristics (tumor stage, histological grade), and therapeutic interventions (surgery, chemotherapy, radiotherapy). CI, confidence interval; HR, hazard ratio.
Association of age with prognosis in stage II colon cancer: tumor stage stratification analysis
In a stratified analysis of T3 and T4 stage II colon cancer, we found that age was strongly associated with prognosis. The Kaplan-Meier curves demonstrate that among patients with T3 stage, the <40 group had the highest survival and the >80 group the lowest (log-rank P<0.001, Figure 3A). The same trend was observed in the T4 group (log-rank P<0.001, Figure 3B). Among patients with T3 tumors, mortality risk increased progressively with age after adjusting for sociodemographic, clinicopathological, and therapeutic factors. Compared to the reference group (<40 years), the HRs were 1.46 (40–49 years), 2.19 (50–59 years), 3.30 (60–69 years), 6.33 (70–79 years), and 13.51 (≥80 years, Table 4).
Table 4
| Age at diagnosis (years) | No. of patients | number of deaths | HR (95% CI)† | HR (95% CI)‡ | HR (95% CI)§ |
|---|---|---|---|---|---|
| T3 | |||||
| <40 | 501 | 39 (7.78) | Reference | Reference | Reference |
| 40–49 | 1,438 | 161 (11.2) | 1.48 (1.04–2.11) | 1.49 (1.05–2.12) | 1.46 (1.03–2.08) |
| 50–59 | 3,334 | 556 (16.8) | 2.22 (1.60–3.08) | 2.23 (1.60–3.09) | 2.19 (1.57–3.04) |
| 60–69 | 4,571 | 1,115 (24.4) | 3.37 (2.44–4.65) | 3.39 (2.45–4.69) | 3.30 (2.39–4.57) |
| 70–79 | 4,693 | 1,962 (41.8) | 6.48 (4.70–8.94) | 6.52 (4.73–8.99) | 6.33 (4.59–8.73) |
| ≥80 | 5,108 | 3,596 (70.3) | 13.99 (10.16–19.27) | 14.05 (10.20–19.35) | 13.51 (9.79–18.63) |
| T4 | |||||
| <40 | 156 | 32 (20.5) | Reference | Reference | Reference |
| 40–49 | 346 | 83 (24.0) | 1.15 (0.76–1.73) | 1.13 (0.75–1.70) | 1.10 (0.73–1.65) |
| 50–59 | 809 | 268 (33.1) | 1.67 (1.16–2.41) | 1.66 (1.15–2.40) | 1.53 (1.06–2.21) |
| 60–69 | 965 | 440 (45.6) | 2.54 (1.77–3.63) | 2.56 (1.79–3.66) | 2.30 (1.60–3.29) |
| 70–79 | 1,016 | 605 (59.5) | 3.61 (2.53–5.16) | 3.61 (2.53–5.15) | 3.00 (2.10–4.30) |
| ≥80 | 1,083 | 890 (82.2) | 6.59 (4.62–9.40) | 6.51 (4.56–9.28) | 4.90 (3.42–7.01) |
Data are presented as number (%). †, adjusted for race, gender, and marital status. ‡, adjusted for demographic factors (race, gender, marital status) and clinical characteristics (tumor stage, histological grade). §, adjusted for demographic factors (race, gender, marital status), tumor characteristics (stage, histological grade), and treatments received (surgery, chemotherapy, radiotherapy). CI, confidence interval; HR, hazard ratio; T, tumor.
Discussion
This study provides new insights into the prognosis of young patients with colon cancer. It is intriguing that despite presenting with more advanced T stages and higher histologic grades, younger patients with stage II disease showed longer overall survival, a finding that merits further exploration.
The prognostic implications for younger individuals diagnosed with colon cancer remain controversial. It has been proposed that these patients may experience a less favorable prognosis (19,20). However, this study demonstrated a persistent association between younger age and longer overall survival in patients with stage II colon cancer, which remained significant after adjustment for key clinicopathologic variables and treatment modalities, irrespective of chemotherapy administration.
First, our results align with previous research by demonstrating that patients younger than 40 years present with a higher prevalence of T4 stage and high-grade (III/IV) tumors, suggesting that youth is associated with adverse clinicopathologic features. Earlier studies extend these observations, noting that younger colon cancer patients are often diagnosed with more advanced disease, larger tumors, and poorer differentiation (19-21). Our study further highlights this paradox: despite a higher incidence of adverse prognostic factors in patients under 40, the risk of death increased with advancing age. Notably, no statistically significant difference in mortality risk was observed between the under-40 and 40–49 age groups.
The higher chemotherapy rate observed in younger patients (41.8% in those under 40 vs. 2.7% in those over 80) may contribute to their survival advantage, likely reflecting a more aggressive treatment approach guided by their better perceived tolerance. However, the persistence of the survival trend across both chemotherapy and non-chemotherapy subgroups indicates that this advantage is not solely attributable to treatment intensity. Instead, it suggests the potential influence of intrinsic factors, such as distinct tumor biology, genetic background, or lifestyle, which may underpin the more favorable prognosis in younger patients despite their adverse clinicopathologic profile.
Tomoki Abe et al. (22) discovered that patients under 40 years old with colorectal cancer have a similar prognosis to older patients. However, the study only included 980 patients and categorized them solely based on age (under 40 and over 40). It is important to note that there is significant heterogeneity within the group of patients over 40. Xie et al. (20) find that youth increased the risk of lymph node metastasis in patients with early-stage colon cancer. Rodriguez et al. (21) discovered that younger cancer patients exhibit greater invasiveness and more advanced disease than older patients, but their survival outcomes have improved.
This study has several inherent limitations that should be considered. Its retrospective design, the potential for unmeasured confounding, and the lack of detailed baseline and treatment data in the SEER database may affect the interpretation of our findings. The absence of specific chemotherapeutic regimens and surgical details precludes a nuanced analysis of how treatment intensity influences survival. To overcome these constraints, future prospective studies with comprehensive data collection on lifestyle, comorbidities, and treatment specifics are warranted. Furthermore, integrating molecular and genetic profiling could elucidate the underlying biological mechanisms driving the age-related survival disparities observed in this study. We also acknowledge that our analysis only adjusted for T stage and histological grade, while other key high-risk factors (e.g., lymphovascular invasion, perineural invasion, bowel obstruction) were not assessed. Although we included only N0 patients in this study, the impact of the number of examined lymph nodes was not investigated. Inadequate lymph node harvest could potentially affect accurate staging, and this is therefore a limitation of our study. Finally, no sensitivity or robustness analyses (e.g., propensity score matching or inverse probability of treatment weighting) were performed in our study. The absence of such analyses may affect the assessment of the stability of our findings.
In summary, our findings suggest that younger age may be associated with improved survival in stage II colon cancer patients, but this finding requires further validation in future studies with larger cohorts and more comprehensive adjustments. This critical insight necessitates a more personalized management approach for young patients and directs future research toward elucidating the distinct molecular drivers and tumor biology that may confer this survival advantage.
Conclusions
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2026-1-0088/rc
Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2026-1-0088/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2026-1-0088/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was approved by the Ethics Committee of The First Affiliated Hospital of Gannan Medical University.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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