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. Cancer 2007. © 2007 American Cancer Society.

To identify predictive factors for locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) in patients treated with chemoradiation and surgery for rectal cancer. Between 1989 and 2001, 470 patients with rectal cancer were treated with preoperative (89%) or postoperative (11%) chemoradiation and mesorectal excision. Median radiation dose was 45 Gy; 97% received concurrent infusional 5-fluorouracil, and 65% received adjuvant chemotherapy. Median follow-up interval was 5.7 years. The 5-year rates of freedom from LR, freedom from DM, and OS were 90%, 79%, and 80%, respectively. On univariate analysis, significant predictors of LR were female sex, clinical T stage, pathologic T and N stages, and positive radial margin. Significant univariate predictors of DM were circumferential extent of tumor, tumor immobility, lymphovascular invasion, perineural involvement, and pathologic T and N stages. Significant univariate predictors of lower OS were age, circumferential extent of tumor, shorter distance from anal verge, tumor size, tumor immobility, anal canal involvement, lymphovascular invasion, perineural involvement, positive radial margin, and pathologic T and N stages. On Cox multivariate analysis, female sex and pathologic T and N stages independently predicted for LR; pathologic T and N stages independently predicted for DM; and age, circumferential extent of tumor, positive radial margin, and pathologic T and N stages independently predicted for lower OS. Pathologic T and N stages significantly predicted for all 3 end points (LR, DM and OS) on multivariate analysis. Investigations of more aggressive adjuvant chemotherapy appear warranted for pathologic stage T3/T4 or N1/2 rectal cancer.