Risk of second primary malignancies after adjuvant chemotherapy for colon cancer

Advances in adjuvant chemotherapy have improved survival in patients with stage II-III colon cancer (CC). However, concerns have emerged regarding the risk of second and subsequent primary malignancies (SPMs) based on preclinical data and registry-based studies. This study evaluated the incidence of SPMs among CC survivors in relation to adjuvant chemotherapy type.

This retrospective, population-based cohort study included 18,383 patients with stage II-III CC who were treated between 2010 and 2022. Patients were categorized based on three adjuvant treatments: (1) no chemotherapy, (2) fluorouracil or capecitabine alone, and (3) fluorouracil or capecitabine with oxaliplatin. Standardized incidence ratios (SIRs) for SPMs were calculated using national cancer registry data.

In an analysis of all 18,383 patients with stage II and III CC who had up to 11.5 years of follow-up, those who received with fluorouracil or capecitabine plus oxaliplatin had a higher overall risk of SPMs (SIR, 1.5; 95% confidence interval, 1.4-1.6) compared with SIRs of 1.1 (95% confidence interval, 1.0-1.2) in patients who did not receive chemotherapy or who received treatment without oxaliplatin. This elevated risk persisted across both stages and was most pronounced for colorectal SPMs. At 10 years, the cumulative SPM incidence reached 14.6% in the oxaliplatin group versus 12.5% and 11.0% in the other two groups, respectively. Oxaliplatin-treated patients had the highest second CC risk (SIR, 2.2).

Oxaliplatin-based adjuvant chemotherapy was associated with a heightened long-term risk of SPMs, particularly second colorectal cancers. These findings highlight the need for risk-adapted survivorship care strategies.