Prognostic Impact of Tumor Regression and Downstaging After Neoadjuvant Therapy in Rectal Cancer.

Background & Objective: Rectal cancer is a common malignancy associated with substantial morbidity. Neoadjuvant chemoradiotherapy (CRT) is the standard treatment for locally advanced disease, often resulting in tumor regression and downstaging. This study aimed to evaluate the relationship between these response patterns and patient prognosis. Methods: A retrospective cohort study was conducted on 200 rectal cancer patients treated with neoadjuvant therapy between 2022 and 2024 at a private pathology laboratory in Isfahan, Iran. Tumor regression was graded using the Dworak system, and downstaging was assessed according to AJCC/UICC-TNM criteria. Patients were followed to evaluate associations with mortality and three-year disease-free survival (DFS). Results: Neither downstaging nor tumor regression significantly predicted disease-free survival in linear models, with downstaging showing F = 0.828 (p = 0.364) and regression yielding R² = 0.001 (p = 0.658). However, logistic regression analysis demonstrated that tumor regression significantly predicted mortality (B = 0.568, p = 0.046, Exp(B) = 1.765), whereas downstaging was not significant (B = -0.290, p = 0.600). The model explained 2.2%-4.5% of the variance in mortality and showed acceptable fit (Hosmer-Lemeshow χ² = 3.418, p = 0.491). Conclusion: Tumor biology and lymph node involvement appear to be stronger predictors of prognosis than regression or downstaging alone. Neither parameter significantly predicted disease-free survival. However, tumor regression was significantly associated with mortality, whereas downstaging was not.