Pathological Response of Locally Recurrent Rectal Cancer to Neoadjuvant Chemoradiotherapy

Objectives: The primary objective was to elucidate the apoptotic response of locally recurrent rectal cancer (LRRC) to neoadjuvant chemoradiotherapy (CRT) using M30 CytoDeath immunostaining. Secondary objectives were to examine its association with tumor regression grade (TRG), tumor size reduction, and long-term outcomes. Methods: This retrospective study included nine patients who underwent CRT followed by radical surgery for LRRC between 2012 and 2020. TRG was evaluated according to the Japanese Classification of Colorectal Carcinoma. Apoptosis was assessed with M30 CytoDeath immunostaining, in which the proportion of stained cells was classified as score 0 (0-33%), score 1 (34-66%), score 2 (67-99%), and score 3 (100%). Tumor size reduction, R0 resection rate, and survival outcomes were also analyzed. Results: No patient achieved pathological complete response; most were TRG 1. By M30 CytoDeath staining, no case had a score ≥2, while score 0 was dominant. A few patients showed score 1, including those treated with oxaliplatin or irinotecan in addition to tegafur and uracil/leucovorin. Tumor size reduction was achieved in most patients, with an R0 resection rate of 77.8%. Among R0 cases, 5-year local re-recurrence-free and 3-year disease-free survival rates were 42.9% and 14.3%, respectively. Conclusions: Direct assessment of apoptosis demonstrated that LRRC is resistant to CRT-induced apoptosis. This resistance likely contributes to high local and distant recurrence after surgery, underscoring the need to develop more effective perioperative strategies for LRRC.