Predictors of tumor downsizing and regression with preoperative radiotherapy alone and with concomitant tegafur/uracil (UFT) for resectable advanced rectal adenocarcinoma

Background/Aims: Predictors of sensitivity to preoperative radiotherapy (RT) may differ from those of chemo-radiotherapy (CRT). This study attempts to evaluate retrospectively the significance of apoptosis-related and proliferative indexes in biopsy specimens obtained before treatment as predictors of sensitivity to RT or to CRT for locally advanced rectal adenocarcinoma. Methodology: The subjects were 96 patients with clinical T3-4/Nx/MO adenocarcinoma of the middle third or lower third of the rectum. Sixty-one patients were treated with preoperative RT alone (20 Gy in 10 fractions) [RT group] during 1991-1998, and 35 patients received concurrent oral tegafur/uracil (UFT) [CRT group] since 1999. Radical surgery including THE and pelvic nerve preservation with 15 Gy of intraoperative RT was performed two weeks after completion of the preoperative radiation. We evaluated apoptotic index (AI) and p53, p21 and Ki67 protein expression in the biopsy specimens, and histological differentiation, pathologic regression in the resected specimens and the degree of tumor shrinkage based on the double contrast barium enema images. Results: AI-positivity, p53-negativity, p21-positivity and well differentiated adenocarcinoma were predictors of high sensitivity in RT group, whereas Al-positivity alone was the predictor in CRT group. The addition of UFT to RT increased sensitivity in patients with p53-positivity, p21-negativity and moderately differentiated adenocarcinoma. Conclusions: Predictors of sensitivity are different between RT and CRT.