Survival paradox and effect of adjuvant chemotherapy for high-risk Stage II and low-risk Stage III colorectal cancer

Abstract Purpose: High-risk Stage II may have a worse prognosis than low-risk Stage III colorectal cancer and there are limited reports examining the efficacy of adjuvant chemotherapy in Stage II and III subgroups. Methods: Using a multicenter database, 598 colorectal cancer patients who underwent laparoscopic colorectal resection and were pathologically diagnosed with high-risk Stage II (T4N0) or low-risk Stage III (T1-2N1, T1-2N2, T3N1) between April 2016 and December 2022 were retrospectively reviewed. Results: Fewer patients received adjuvant chemotherapy in the T4N0 group (54.7/45.0/44.7/27.7%, p<0.001). The T4N0 group had significantly worse 5-year relapse-free survival (RFS) (67.0 vs. 95.5%, p<0.01) and 5-year overall survival (OS) (56.5 vs. 91.7%, p<0.01) than the T1-2N1 group. The T4N0 group had significantly worse 5-year RFS (67.0% vs. 95.5%, p<0.01) and 5-year OS (56.5% vs. 91.7%, p<0.01) than the T1-2N1 group. Five-year OS was significantly better in the T1-2N1 and T3N1 groups with than without adjuvant chemotherapy (p<0.032, p<0.001, respectively), but not in the T4N0 group. Conclusions: The present multicenter study showed that high-risk Stage II colorectal cancer may have a worse prognosis than low-risk Stage III colorectal cancer. Preoperative chemotherapy should be considered to improve the prognosis of T4N0 colorectal cancer.