Total neoadjuvant therapy (TNT) enhances tumor regression in individuals with locally advanced rectal cancer (LARC) relative to standalone neoadjuvant chemoradiotherapy. The influence of TNT on overall patient outcomes remains incompletely explored. This retrospective review involved cases of LARC managed at a major oncology facility. A group of 311 patients underwent chemoradiotherapy (chemoRT) exclusively as neoadjuvant therapy, with scheduled postoperative chemotherapy, while 313 patients were treated with TNT, consisting of upfront chemotherapy based on fluorouracil and oxaliplatin followed by chemoradiotherapy prior to surgery. Subsequently, participants proceeded to total mesorectal excision or enrollment in a watch-and-wait strategy. Complete response (CR) rates post-neoadjuvant treatment—defined as pathologic CR or sustained clinical CR for 2 years—were evaluated using the χ² test. Kaplan-Meier curves with log-rank testing were applied to analyze disease-free survival (DFS), local recurrence-free survival, distant metastasis-free survival, and overall survival. Additional assessment of DFS employed Cox proportional hazards models. Complete response occurred in 20% of chemoRT cases versus 27% in the TNT arm (P=.05). No significant differences emerged in DFS, local recurrence-free survival, distant metastasis-free survival, or overall survival. The neoadjuvant approach did not impact disease-free survival (hazard ratio [HR] 1.3; 95% confidence interval [CI] 0.93-1.80; P = .12). TNT fails to extend survival beyond that achieved with neoadjuvant chemoradiotherapy combined with planned adjuvant chemotherapy; nevertheless, its superior response rates could enable organ preservation in a greater number of LARC cases.
