Pathological Tumor–Nodal Response Patterns After Neoadjuvant Treatment for Rectal Cancer: Prognostic Impact of Residual ypN-Positive Disease

Background/Objectives: Pathological response to neoadjuvant treatment in rectal cancer may differ between the primary tumor and regional lymph nodes, and the prognostic implications of this discordance remain incompletely defined. We evaluated oncological outcomes according to combined pathological tumor–nodal response patterns, with particular emphasis on complete primary-tumor regression with residual ypN-positive disease. Methods: A total of 215 patients with nonmetastatic rectal adenocarcinoma who received neoadjuvant treatment followed by curative-intent resection were retrospectively analyzed. Patients were classified as ypT0N0 (n = 34), ypT0N+ (n = 13), residual primary tumor/ypN0 (n = 119), or residual primary tumor/ypN+ (n = 49). The primary endpoint was time to recurrence (TTR). Kaplan–Meier, Cox, Firth penalized Cox, competing-risk, and sensitivity analyses were performed. Results: Median follow-up was 70.0 months. Recurrence occurred in 2/34 (5.9%), 6/13 (46.2%), 17/119 (14.3%), and 18/49 (36.7%) patients, respectively. Estimated 5-year recurrence-free probabilities were 90.1%, 53.8%, 81.6%, and 46.3%, respectively (log-rank p < 0.0001). Compared with ypT0N0, recurrence hazard was significantly higher for ypT0N+ (adjusted hazard ratio 7.56, 95% confidence interval 1.49–38.40; p = 0.015) and residual primary tumor/ypN+ (adjusted hazard ratio 7.10, 95% confidence interval 1.64–30.83; p = 0.009). In an analysis restricted to patients with baseline cT3N1 disease, the association for ypT0N+ remained evident (adjusted hazard ratio 6.34, 95% confidence interval 1.19–33.79; p = 0.031). Competing-risk analyses were concordant, and all documented recurrences in the ypT0N+ group involved distant metastasis. Conclusions: In this cohort, residual ypN-positive disease despite complete pathological regression of the primary tumor was associated with an increased risk of recurrence. Given the small number of patients with ypT0N+ disease, these findings should be interpreted cautiously and require validation in larger independent cohorts.