Older Age Threshold for Oxaliplatin Benefit in Stage II to III Colorectal Cancer

Abstract

Importance: Colorectal cancer is a leading cause of cancer mortality, with increasing incidence in older adults. Oxaliplatin-based adjuvant chemotherapy is standard for stage II to III colorectal cancer, but its benefit in older patients remains unclear.

Objective: To investigate whether there is an optimal age threshold for a survival benefit of adding oxaliplatin to fluoropyrimidine-based adjuvant chemotherapy in older patients with stage II to III colorectal cancer.

Design, setting, and participants: This population-based, retrospective cohort study using data from the Korea Health Insurance Review and Assessment Service included patients who underwent curative resection for stage II to III colorectal cancer and received adjuvant chemotherapy between January 2014 and December 2016. Participants were followed up until date of death or April 30, 2024, whichever occurred earlier.

Exposures: Oxaliplatin-based adjuvant chemotherapy compared with fluoropyrimidine-only chemotherapy.

Main outcomes and measures: The primary outcome was overall survival, analyzed using Cox proportional hazards regression and propensity score matching. Age thresholds from 60 to 80 years were systematically assessed to identify the optimal cutoff for oxaliplatin benefit. The association between chemotherapy discontinuation and oxaliplatin use was evaluated using multivariate regression analysis.

Results: Among a total of 53 147 patients, 8561 (mean [SD] age, 63.2 [11.2] years; 5084 [59.4%] male) were included in this study (stage II: 2913 [34.0%]; stage III: 5648 [65.9%]). Oxaliplatin was not associated with improved survival among patients with stage II disease across all age thresholds (adjusted hazard ratios [AHRs] ranged from 0.71 [95% CI, 0.34-1.50] to 1.09 [95% CI, 0.73-1.64]). In patients with stage III disease, oxaliplatin was associated with significantly improved survival up to age 70 years (AHR, 0.59; 95% CI, 0.46-0.77; P < .001), with a 5-year overall survival rate of 84.8% in the oxaliplatin group and 78.1% in the nonoxaliplatin group (P = .003). In patients older than 70 years, oxaliplatin was not associated with survival (AHR, 0.85; 95% CI, 0.67-1.07; P = .18). Multivariate regression analysis showed that oxaliplatin use was significantly associated with chemotherapy discontinuation in patients older than 70 years with stage III disease (adjusted odds ratio [AOR], 1.55; 95% CI, 1.19-2.03; P = .001), whereas no such association was observed in patients aged 70 years or younger (AOR, 1.22; 95% CI, 0.93-1.62; P = .16).

Conclusions and relevance: In this population-based cohort study, oxaliplatin addition was associated with significantly improved survival among patients with stage III colorectal cancer aged 70 years or younger but not in those older than 70 years. There was no association with improved survival among patients with stage II disease regardless of age. Moreover, in patients older than 70 years with stage III disease, oxaliplatin use was significantly associated with chemotherapy discontinuation.

Figure 1.. Flow Diagram for the Inclusion of the Study Population

Includes patients who underwent curative radical resection for colorectal cancer between 2014 and 2016 from the Korea Health Insurance Review and Assessment Service’s National Quality Assessment program database.

Figure 2.. Adjusted Hazard Ratios (AHRs) for Overall Survival by Use of Oxaliplatin-Combined vs Nonoxaliplatin Adjuvant Chemotherapy, Stratified by Cancer Stage and Age at Diagnosis

Analysis was performed using Cox proportional hazards regression models adjusted for age, sex, body mass index, emergency operation for colorectal cancer, Charlson Comorbidity Index, American Society of Anesthesiologists classification, tumor histology, lymph node count, chemotherapy regimen, and treatment.

Figure 3.. Kaplan-Meier Survival Curves by Age and Oxaliplatin Use in Patients With Stage III Disease

Kaplan-Meier estimates comparing overall survival between oxaliplatin and nonoxaliplatin adjuvant chemotherapy before and after propensity score matching (PSM). P values were derived from log-rank tests.