Is Adjuvant Chemotherapy Necessary for All Patients with pT3N0 Rectal Cancer after Upfront Surgery? A Multicenter Retrospective Study

Purpose: The role of adjuvant chemotherapy (ACT) in pathologic T3N0 (pT3N0) rectal cancer, which has a favorable prognosis, remains controversial because high-risk groups for recurrence are not well defined. This study investigated prognostic factors for survival in this patient group and evaluated the benefit of ACT based on these factors. Materials and Methods: This retrospective study analyzed 352 patients with pT3N0 rectal cancer who underwent upfront radical surgery at three referral hospitals between November 2003 and December 2020. A multivariable Cox regression model was used to identify the prognostic factors for 5-year recurrence-free survival (RFS). Patients were categorized as high or low risk based on these factors, and survival outcomes were compared between those who received ACT and those who did not, using the log-rank test. Results: Median follow-up was 52.8 months. 193 (54.8%) patients received ACT. Multivariable analysis revealed that ACT, circumferential resection margin (CRM) ≤ 2mm, vascular invasion, and perineural invasion were independent predictors of 5-year RFS. In patients with ≥ 1 risk factor, ACT significantly improved RFS (92.5% vs. 72.8%, hazard ratio HR 0.247, 95% confidence interval CI 0.090-0.683, p < 0.01). In those without risk factors, no significant benefit was observed (98.0% vs. 91.6%, HR 0.272, 95% CI 0.057-1.313, p=0.082). Conclusion: This study identified CRM ≤ 2mm, vascular invasion, and perineural invasion as high-risk features for recurrence in pT3N0 rectal cancer. ACT improved RFS only in patients with these features. While these findings support risk-based ACT administration in this patient population, further validation of our risk stratification system is needed.