Mucinous Rectal Adenocarcinoma Can Be Associated to Tumor Downstaging after Preoperative Chemoradiotherapy Filippo Grillo-Ruggieri, M.D., 1 Giovanna Mantello, M.D., 1 Rossana Berardi, M.D., 1 Massimo Cardinali, M.D., 1 Francesco Fenu, M.D., 1 Giuseppina Iovini, M.D., 1 Maria Montisci, M.D., 1 Letizia Fabbietti, M.D., 1 Cristina Marmorale, M.D., 2 Mario Guerrieri, M.D., 2 Vittorio Saba, M.D., 3 Italo Bearzi, M.D., 4 Rodolfo Mattioli, M.D., 5 Maurizio Bonsignori, M.D., 1 Stefano Cascinu, M.D. 1 1 Dipartimento di Oncologia e Radioterapia Generale, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy 2 Dipartimento delle Malattie Digestive e Chirurgia Generale, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy 3 Patologia Chirurgica, Istituto Nazionale Ricerca e Cura Anziani, Ancona, Italy 4 Dipartimento di Patologia, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy 5 Oncologia, Ospedale Santa Croce, Fano, Italy PURPOSE: The aim of this study was to evaluate down- staging as primary end point, and progression-free survival and overall survival as secondary end points, in rectal adenocarcinoma patients treated with preoperative chemo- radiation. METHODS: One hundred and thirty-six extraper- itoneal adenocarcinoma patients (33 low rectum T2, 74 T3, 29 T4 [without sacral invasion], 25 with mucinous subtype) were treated with posterior pelvis preoperative radiotherapy (5040 cGy total dose, 180 cGy/fr, 5 fr/w, 10– 15 MV linac X-rays) and concomitant 5-fluorouracil-based chemotherapy. After 6 to 8 weeks patients underwent surgery and prechemoradiation clinical stage was com- pared with pathologic stage to evaluate downstaging in each patient. Seventy-four patients received adjuvant chemotherapy. Median follow-up was 39 months (4–84). RESULTS: Forty-four patients had macroscopic complete response, 52 patients had partial response, 37 patients showed no change and 3 patients had progression. At multivariate analysis only histotype showed correlation with downstaging (hazard ratio=0.350 and 0.138 – 0.885 95 percent confidence interval) because of the evidence for poor downstaging in mucinous subtype. There were no significant differences in overall survival and progression- free survival between adenocarcinoma and mucinous subtype. CONCLUSIONS: The main finding is that mucin- ous histology is associated with poor downstaging after preoperative chemoradiation but this poor response was not associated with worse outcome in this small study. The good outcome for mucinous histology is at odds with other reports in the literature and requires further study. [Key words: Mucinous histology; Rectal cancer; Multimodality therapy; Radiotherapy; Downstaging] INTRODUCTION Extraperitoneal rectal cancer is routinely treated both in Europe and the United States with neoadjuvant preoperative radiotherapy. Several series have associ- Correspondence to: Filippo Grillo-Ruggieri, M.D., Dipartimento di Oncologia e Radioterapia Generale, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy, e-mail: filippo.grillo. ruggieri@galliera.it Dis Colon Rectum 2007; 50: 1594–1603 DOI: 10.1007/s10350-007-9026-1 * American Society of Colon and Rectal Surgeons Published online: 11 September 2007 1594