SOCCER: A randomized phase II trial comparing complete clinical response after short course radiation or chemoradiation and consolidation chemotherapy in rectal cancer.

3618 Background: The preferred total neoadjuvant treatment (TNT) regimen for an intentional watch-and-wait (W&W) approach in patients with rectal cancer is long course chemoradiation (LCRT) and consolidation chemotherapy (CNCT). The role of short course radiation (SCRT) and CNCT in this context is not well defined. The shorter treatment time of SCRT has advantages, especially in resource-constrained settings. This study aimed to select the more promising of the two TNT strategies for a W&W approach in patients with rectal cancer for further phase III evaluation. Methods: This dual-center, randomized phase II trial was conducted in Chennai and Vellore, India. Patients with rectal adenocarcinoma within 8cm of the anal verge, T3N0 or T1-3N+ on magnetic resonance imaging (MRI) who required neoadjuvant radiation and surgery, were randomized to one of two arms: Arm A - LCRT (54Gy with capecitabine) + 6 cycles of CAPOX (capecitabine + oxaliplatin), Arm B - SCRT (25Gy) + 6 cycles of CAPOX. Tumor response was assessed at 24 weeks from completion of radiation by digital rectal examination, sigmoidoscopy and MRI and categorized by a pre-defined criterion. Primary end-point was cCR or near cCR. Patients with a cCR at first assessment or at a second assessment 12 weeks after a near cCR were offered W&W. Based on Simon’s randomized phase II pick-the-winner design, 40 patients were required to achieve a 90% probability of correct selection, assuming a 50% cCR and a 20% absolute difference, without formal superiority testing. Secondary endpoints included adverse events, treatment compliance, post-operative complications, 2-year organ preservation, local regrowth, disease-free survival, diagnostic performance of response assessment criteria, and quality of life. Results: Among 46 patients randomized between 2022 and 2025, primary endpoint was assessed in 43 (modified intention-to-treat population). Median age (range), proportion of T3, node positive tumors and mesorectal fascia involvement were 54 years (27-69), 86.3%, 54.5%, 63.6% and 49 years (31-68), 86.9%, 56.5%, 60.8% in Arm A and B, respectively. For primary and short-term secondary endpoints, see Table. Conclusions: SCRT + CNCT was superior to LCRT + CNCT in inducing cCR/near cCR in patients with rectal cancer and emerged as the preferred regimen for further evaluation of an intentional W&W approach in a phase III study. Clinical trial information: CTRI: 2021/01/030370. End-point Arm A Arm B No. of complete + near complete clinical response 8/20 (40%) 17/23 (73.9%) Adverse events ≥Grade 3 During Radiation During CNCT 2 (in 20 patients)43 in 108 cycles 1 (in 23 patients)26 in 138 cycles No. of pts with Relative dose intensity of CNCT <85% 6 (33.3%) 11 (47.8%) No. of pts with CNCT delayed ≥3 days in ≥2 cycles 5 (27.7%) 2 (8.6%) Median no. of CNCT cycles 6 6 Post-operative complicationsClavien-Dindo ≥3 2 in 11 patients 0 in 6 patients Treatment related death 1 0