CLINICAL INVESTIGATION Rectum INTERVAL BETWEEN SURGERYAND NEOADJUVANT CHEMORADIATION THERAPY FOR DISTAL RECTAL CANCER: DOES DELAYED SURGERY HAVE AN IMPACT ON OUTCOME? ANGELITA HABR-GAMA, M.D., PH.D.,* RODRIGO OLIVA PEREZ, M.D., PH.D., y IGOR PROSCURSHIM, M.S., y RAFAEL MIYASHIRO NUNES DOS SANTOS, M.S., y DESIDERIO KISS, M.D., PH.D.,* y JOAQUIM GAMA-RODRIGUES, M.D., PH.D.,* y AND IVAN CECCONELLO, M.D., PH.D.* y * Habr-Gama Research Institute, Sa ˜o Paulo, SP, Brazil; and y Department of Gastroenterology, University of Sa ˜o Paulo School of Medicine, Sa ˜o Paulo, SP, Brazil Background: The optimal interval between neoadjuvant chemoradiation therapy (CRT) and surgery in the treat- ment of patients with distal rectal cancer is controversial. The purpose of this study is to evaluate whether this interval has an impact on survival. Methods and Materials: Patients who underwent surgery after CRT were retrospectively reviewed. Patients with a sustained complete clinical response (cCR) 1 year after CRT were excluded from this study. Clinical and path- ologic characteristics and overall and disease-free survival were compared between patients undergoing surgery 12 weeks or less from CRT and patients undergoing surgery longer than 12 weeks from CRT completion and between patients with a surgery delay caused by a suspected cCR and those with a delay for other reasons. Results: Two hundred fifty patients underwent surgery, and 48.4% had CRT-to-surgery intervals of 12 weeks or less. There were no statistical differences in overall survival (86% vs. 81.6%) or disease-free survival rates (56.5% and 58.9%) between patients according to interval (#12 vs. >12 weeks). Patients with intervals of 12 weeks or less had significantly higher rates of Stage III disease (34% vs. 20%; p = 0.009). The delay in surgery was caused by a suspected cCR in 23 patients (interval, 48 ± 10.3 weeks). Five-year overall and disease-free survival rates for this subset were 84.9% and 51.6%, not significantly different compared with the remaining group (84%; p = 0.96 and 57.8%; p = 0.76, respectively). Conclusions: Delay in surgery for the evaluation of tumor response after neoadjuvant CRT is safe and does not negatively affect survival. These results support the hypothesis that shorter intervals may interrupt ongoing tumor necrosis. Ó 2008 Elsevier Inc. Rectal cancer, Neoadjuvant therapy, Interval, Surgery, Survival. INTRODUCTION Neoadjuvant chemoradiation therapy (CRT) has been con- sidered the optimal management strategy for patients with distal rectal cancer because of increased local disease control, decreased toxicity rates, and greater rates of sphincter preser- vation (1–3). In addition, CRT leads to significant tumor downstaging, including primary tumor regression and possi- ble lymph node sterilization (4). However, the optimal timing between CRT completion and surgery is undetermined. Rea- sons for this uncertainty are some potential benefits and risks associated with this period between CRT and surgery. Increased intervals could potentially increase the tumor downstaging effect because radiation-induced necrosis appears to be a time-dependent phenomena. However, increased intervals could also allow tumor progression, lead- ing to disease progression and decreased survival. More recently, a nonsurgical approach was considered a possible alternative in highly selected patients with a com- plete clinical response (cCR) (5–7). However, because objec- tive and accurate radiologic studies capable of identifying these patients are unavailable, these patients are closely fol- lowed up and only considered complete responders after at least 12 months of close observation. Therefore, in a propor- tion of these patients, tumor regrowth or residual undetected disease is diagnosed at variable intervals from CRT comple- tion, leading to delayed surgical treatment compared with the usual 6–8-week recommended intervals (8). In this setting, the final disease outcome of patients misdiagnosed with Reprint requests to: Angelita Habr-Gama, M.D., Ph.D., Rua Manuel da No ´brega, 1564 Sa ˜o Paulo, SP, 04001-005 Brazil. Tel: (+55) 11-3887-1757; Fax: (+55) 11-3884-8845; E-mail: gamange@ uol.com.br Conflict of interest: none. Received Oct 2, 2007, and in revised form Nov 3, 2007. Accepted for publication Nov 6, 2007. 1181 Int. J. Radiation Oncology Biol. Phys., Vol. 71, No. 4, pp. 1181–1188, 2008 Copyright Ó 2008 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/08/$–see front matter doi:10.1016/j.ijrobp.2007.11.035