LBA4007 Background: Following the results of randomized trials FFCD 9203 and EORTC 2291, neoadjuvant CT-RT is considered standard treatment for LARC. The ACCORD 12/0405 PRODIGE 2 trial was initiated to optimize this regimen. Methods: Pts with T3 or resectable T4 N0–1-2 M0, rectal adenocarcinoma were randomized to arm A: concurrent RT 45Gy/25f/5 weeks (w) + capecitabine (800mg/m2/bid) or arm B: concurrent RT 50Gy/25f/5w + capecitabine (800mg/m2/bid/5/7days) + oxaliplatine 50mg/m2/w. Resection with Total Mesorectum Excision was scheduled 6 weeks after the end of CT-RT. Adjuvant chemotherapy was optional. 590 patients were needed to show an increase in the pathological complete response (Dworak) rate from 11% (arm A) to 20% (arm B). Circumferential positive rectal margin (CRM R1) was defined as the presence of residual cancer cells within 0 to 1 mm from the perirectal surface. Results: This trial closed in 07/2008 after randomization of 598 pts since 11/2005. Patients characteristics of 586 eligible pts were well balanced: male 66%, median age 61 years, 66% low rectum, 87% T3 stage. Data base was locked in March 2009. Results are reported in Table . Conclusions: The RT 50 capox regimen is compatible with surgery in 98% of cases with no increase in postoperative complication. In the RT 50 arm, there is a trend in favour of a higher rate of pathological complete sterilization and lower rate of positive CRM. These data could contribute to design a new standard preoperative regimen for LARC. 50 Gy/25 F/5 weeks combined with concurrent chemotherapy could be proposed as an efficient schedule. [Table: see text] No significant financial relationships to disclose.