Pathologic Implications of Radial Resection Margin and Perineural Invasion to Adjuvant Chemotherapy after Preoperative Chemoradiotherapy and Surgery for Rectal Cancer: A Multi-Institutional and Case-Matched Control Study

SIMPLE SUMMARY: The significance of the role of adjuvant chemotherapy in patients with rectal cancer treated with neoadjuvant chemoradiation and surgery has yet to be been determined. In this multi-center and case-matched analysis, we evaluated 1799 patients with rectal cancer who received adjuvant chemotherapy after neoadjuvant chemoradiation and total mesorectal excision. Positive surgical margin and perineural invasion were poor prognostic factors after neoadjuvant chemoradiotherapy and curative surgery. Adjuvant chemotherapy significantly decreased recurrences in patients with positive margin or perineural invasion. The role of adjuvant chemotherapy in rectal cancer patients without positive margin and perineural invasion after neoadjuvant chemoradiotherapy and surgery could be limited. ABSTRACT: We assessed the exact role of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CRT) and surgery in rectal cancer patients with positive surgical margin or perineural invasion (PNI). This multi-institutional study included 1799 patients with rectal cancer at cT3-4N0-2M0 stages. Patients were divided into two groups. The high-risk group had a positive margin and/or perineural invasion. The low-risk group showed no positive margin or PNI. Propensity-score matching analysis was performed, and a total of 928 patients, with 464 in each arm, were evaluated. The high-risk group showed significant differences in overall survival (OS, 73.4% vs. 53.9%, p < 0.01) and recurrence-free survival (RFS, 52.7% vs. 40.9%, p = 0.01) at five years between the adjuvant chemotherapy arm and observation arm. The low-risk group showed no significant differences in 5-year OS (p = 0.61) and RFS (p = 0.75) between the two arms. Multivariate analyses showed that age, pathologic N stage, and adjuvant chemotherapy were significantly correlated with OS and RFS in the high-risk group (all p < 0.05). Adjuvant chemotherapy improved OS and RFS more significantly in rectal cancer patients with positive surgical margin or PNI than in those with negative surgical margin and PNI.