ORIGINAL ARTICLE Clinical and Pathologic Predictors of Locoregional Recurrence, Distant Metastasis, and Overall Survival in Patients Treated With Chemoradiation and Mesorectal Excision for Rectal Cancer Prajnan Das, MD, MS, MPH,* John M. Skibber, MD,† Miguel A. Rodriguez-Bigas, MD,† Barry W. Feig, MD,† George J. Chang, MD,† Paulo M. Hoff, MD,‡ Cathy Eng, MD,‡ Robert A. Wolff, MD,‡ Nora A. JanJan, MD,* Marc E. Delclos, MD,* Sunil Krishnan, MD,* Lawrence B. Levy, MS,* Lee M. Ellis, MD,† and Christopher H. Crane, MD* Objectives: To identify predictive factors for locoregional recur- rence (LR), distant metastasis (DM), and overall survival (OS) in patients treated with chemoradiation and surgery for rectal cancer. Methods: Between 1989 and 2001, 470 patients with rectal cancer were treated with preoperative (89%) or postoperative (11%) che- moradiation 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. Results: 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 involve- ment, 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 indepen- dently predicted for DM; and age, circumferential extent of tumor, positive radial margin, and pathologic T and N stages independently predicted for lower OS. Conclusions: Pathologic T and N stages significantly predicted for all 3 end points (LR, DM and OS) on multivariate analysis. Inves- tigations of more aggressive adjuvant chemotherapy appear war- ranted for pathologic stage T3/T4 or N1/2 rectal cancer. Key Words: rectal cancer, predictive factors, local recurrence, metastasis, survival, Cox model (Am J Clin Oncol 2006;29: 219 –224) M ultiple randomized trials have established the role of neoadjuvant and adjuvant radiotherapy and chemother- apy in patients with resected stage T3/T4 or node-positive rectal cancer. 1–4 However, the risks of relapse and death vary widely among rectal cancer patients. 5 Different treatment strategies may be indicated for different groups of rectal cancer patients, on the basis of their risks for local and distant failure and death. For example, patients at a high risk for DM or death may be candidates for more aggressive adjuvant chemotherapy regimens. Clinical and pathologic factors that predict relapse and death can therefore help in the design of risk-adapted therapy for rectal cancer patients. The goal of this study was to identify clinical and pathologic factors that predict for locoregional relapse (LR), distant metastasis (DM), and overall survival (OS) in rectal cancer patients. We performed univariate and multivariate analysis to identify predictive factors in 470 patients treated with mesorectal excision and either neoadjuvant or adjuvant chemoradiation at The University of Texas M. D. Anderson Cancer Center, with a median follow-up interval of over 5 years. PATIENTS AND METHODS The study included all patients (n = 470) with newly diagnosed rectal cancer (located at 12 cm from the anal verge) and no evidence of DM, who were treated with mesorectal excision and either preoperative or postoperative chemoradiation at M. D. Anderson Cancer Center, between From the *Department of Radiation Oncology, †Department of Surgical Oncology, and ‡Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX. Supported in part by grants CA06294 and CA16672 from the National Cancer Institute, Department of Health and Human Services. Presented in part at the American Society of Clinical Oncology Annual Meeting, May 13–17, 2005. Reprints: Prajnan Das, Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 97, Houston, TX 77030. E-mail: PrajDas@mdanderson.org. Copyright © 2006 by Lippincott Williams & Wilkins ISSN: 0277-3732/06/2903-0219 DOI: 10.1097/01.coc.0000214930.78200.4a American Journal of Clinical Oncology • Volume 29, Number 3, June 2006 219