Analysis of Pathologic Complete Response Rates Between Different Neoadjuvant Radiation Treatment Regimens for Rectal Cancer

Abstract

The standard of care for rectal cancer is either long or short course radiation followed by surgery with or without adjuvant chemotherapy. Recently, total neoadjuvant therapy, an approach consisting of giving all chemotherapy and radiotherapy prior to definitive surgery, has been a promising alternative. This study aims to assess the pathologic complete response (pCR) rates among different neoadjuvant treatment regimens and determine if neoadjuvant chemotherapy improves pCR rates.Electronic medical databases were queried to identify rectal cancer patients treated with neoadjuvant therapy at our institution from 2006-2019. Patients were grouped according to neoadjuvant therapy received: long-course chemoradiation (CRT), long-course chemoradiation with chemotherapy (CRT TNT), short-course radiation (SCRT), and short-course radiation with chemotherapy (SCRT TNT). Patients without follow-up data or surgical pathology reports were excluded. pCR was defined as no evidence of disease at surgery. pCR rates were determined and compared using Chi-square analysis.A total of 249 patients were analyzed. Table 1 shows treatment characteristics in each group. There were 200 (80.3%) patients who received CRT, 26 (10.4%) who received CRT TNT, 13 (5.2%) who received SCRT, and 10 (4%) who received SCRT TNT. Initial stage was different between groups, with metastatic patients more likely to receive SCRT TNT (P < 0.001). The median time to surgery were significantly different between groups (P < 0.001). Eleven (42.3%) and 6 (60%) patients received FOLFOX, and 13 (50%) and 4 (40%) of the patients received XELOX for CRT TNT and SCRT TNT, respectively. The remaining patients (7.7%) in the CRT TNT group received Capecitabine. For CRT, 53 (26.5%) patients achieved pCR, 3 (11.5%) in CRT TNT, 1 (7.7%) in SCRT, and 2 (20%) in SCRT TNT. None of these differences were statistically different (P = 0.19). On univariate analysis, age (P = 0.13), clinical T stage (P = 0.13), clinical N stage (P = 0.95), time to surgery (P = 0.82), and presence of chemotherapy in the neoadjuvant regimen (P = 0.22) were not significant predictors for pCR.Total neoadjuvant treatment for rectal cancer did not improve pCR rates over standard chemoradiation or short course radiation alone, which is contrary to what published series suggest. These results maybe be explained in part by the fact that chemotherapy was delivered first and the time from completing radiation to the time of surgery was not significantly different between groups. These data suggest that meaningful gains in pCR rates may be achieve by sequencing chemoradiation earlier in the TNT course. Future studies are needed to investigate this hypothesis.