Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer

BACKGROUND. The objective of this study was to identify predictive factors for pathologic complete response and tumor downstaging after preoperative chemoradiation for rectal cancer. METHODS. Between 1989 and 2004, 562 patients with nonmetastatic rectal adenocarcinoma received preoperative chemoradiation and underwent mesorectal excision. The median radiation dose was 45 Gray (Gy) (range, 19.8-58.6 Gy), 77% of patients received concurrent infusional 5-fluorouracil, 20% of patients received concurrent capecitabine, and 3% of patients received other regimens. RESULTS. Nineteen percent of patients achieved a pathologic complete response (CR), whereas 20% of patients had only microscopic residual disease at surgery, and 61% of patients had macroscopic residual disease at surgery. Downstaging of the tumor stage occurred in 57% of patients. The results from a univariate analysis indicated that tumor circumferential extent >60% (P = .033) and pretreatment carcinoembryonic antigen (CEA) level >2.5 ng/mL (P = .015) were associated significantly with lower pathologic CR rates. The univariate analysis also indicated that tumor circumferential extent >60% (P =.001), pretreatment CEA level >2.5 ng/mL (P =.006), and distance from the anal verge >5 cm (P =.035) were associated significantly with lower downstaging rates. The results from a multivariate logistic regression analysis indicated that greater circumferential extent of tumor (odds ratio [OR], 0.43; P =.033) independently predicted a lower pathologic CR rate. The multivariate logistic regression analysis also indicated that greater circumferential extent of tumor (OR, 0.49; P = .020) and greater distance from the anal verge (OR, 0.46; P =.010) independently predicted a lower downstaging rate. CONCLUSIONS. Circumferential extent of tumor, CEA level, and distance from the anal verge predicted for the pathologic response to preoperative chemoradiation for patients with rectal cancer. Therefore, these factors may be used to predict outcomes for patients, to develop risk-adapted treatment strategies, and to target patients who participate in trials of newer therapies.