Adjuvant Chemotherapy After Neoadjuvant Chemoradiation and Proctectomy Improves Survival Irrespective of Pathologic Response in Rectal Adenocarcinoma: A Population-Based Cohort Study

Background: This study sought to determine whether adjuvant chemotherapy (AC) compared to no AC (noAC) after neoadjuvant chemoradiation (CRT) and resection for rectal adenocarcinoma prolongs survival. Current guidelines from expert groups are conflicting, and data to support administering AC to patients who received neoadjuvant CRT are lacking. Methods: 19867 patients met inclusion/exclusion criteria. Mean age was 58.6±12.0 years, and 12396 (62.4%) were males. Complete response (CR) was documented in 3801 (19.1%) patients and 8167 (41.1%) received AC. The cohort was stratified into pathological complete (pCR, N=3,801) and incomplete (pIR, N=16,066) subgroups, and pIR further subcategorized into ypN0 (N=10,191) and ypN+ (N=5,875) subgroups. After propensity score matching, AC was associated with improved OS in the pCR subgroups (mean 139.1±1.9 vs. 134.0±2.2 months; p<0.001), in pIR ypN0 subgroup (141.6±1.5 vs. 129.9±1.2 months, p<0.001) and in pIR ypN+ subgroup (155.9±5.4 vs. 126.5±7.6 months; p<0.001). Results: AC was associated with improved OS in patients who received neoadjuvant CRT followed by proctectomy for clinical stages II and III rectal adenocarcinoma. This effect persisted irrespective of pathological response status. Conclusions: AC following neoadjuvant CRT and surgery is associated with improved OS in patients with rectal adenocarcinoma. These findings warrant adoption of AC after neoadjuvant CRT and surgery for clinical stage II and III rectal adenocarcinoma.