Partial Pathologic Response and Nodal Status as Most Significant Prognostic Factors for Advanced Rectal Cancer Treated With Preoperative Chemoradiotherapy

BACKGROUND: This study evaluated the impact of tumor regression grading (TRG) and other pathologic variates in a cohort of rectal carcinoma patients treated with neoadjuvant chemoradiotherapy (CRT). The value of a grading less than pCR for predicting survival is unknown. Tumor budding has not been systematically studied in rectal cancer after neoadjuvant therapy. METHODS: Pathologic risk factors for survival were evaluated on surgical specimens of 237 patients with stages I, II, and III rectal cancer treated between 1996 and 2006. All patients underwent preoperative CRT followed by surgical resection 6-8 weeks later. TRG, tumor grade, budding, venous invasion, radial margin, and nodal status were evaluated. The prognostic value of TRG categories was calculated with Cox regression models and validated with resampling methods. RESULTS: TRG of <25% occurred in 61 (25.7%) and a complete response in 39 (16.4%) of the resected specimens. TRG of <25% was shown to be a statistically significant predictor for cancer-specific survival (CSS) and recurrence-free survival (RFS) compared to TRG ≥25% (P = 0.013). Tumor budding was present in 24 (10.1%) of the patients and was negatively associated with CSS (P = 0.013). Lymph node involvement was observed in 83 (35.0%) patients. TRG and nodal status (P < 0.001) were the most significant predictors associated with outcome. CONCLUSION: Partial pathologic response ≥25% was a superior predictor compared to pCR for improved survival after preoperative CRT. CSS and RFS were adversely affected by the presence of lymph node metastases.