Treatment Adequacy and Baseline Risk Modify the Association Between Adjuvant Chemotherapy and Survival After Pathological Complete Response in Rectal Cancer

The role of adjuvant chemotherapy (ACT) in patients with locally advanced rectal cancer (LARC) who achieve pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) remains controversial, and it is unclear whether pCR represents a uniformly low-risk state with respect to long-term outcomes. We retrospectively analyzed consecutive LARC patients who achieved pCR following nCRT and radical surgery between 2017 and 2022. Survival outcomes were assessed according to postoperative ACT administration, treatment adequacy (≥ 4 cycles vs. < 4 cycles), and baseline risk features. Among 1069 patients treated with nCRT and surgery, 251 (23.5%) achieved pCR. After a median follow-up of 49 months, no statistically significant differences in overall survival (OS) or disease-free survival (DFS) were observed between patients who received ACT and those who did not. In contrast, patients who completed an adequate course of ACT (≥ 4 cycles) demonstrated improved 4-year OS and DFS compared with those receiving fewer cycles or no ACT. This association was largely confined to patients with baseline high-risk features, while no significant survival differences were observed between different ACT regimens. These findings suggest that pCR does not represent a biologically homogeneous or uniformly low-risk condition in LARC. Adequate postoperative chemotherapy may confer survival benefit in selected high-risk patients. A risk-adapted approach to ACT warrants further investigation and prospective validation.