Neoadjuvant short-course radiotherapy combined with CAPOX and PD-1 inhibitor for MSS/pMMR high-risk locally advanced colon cancer: A randomized, prospective, multicentre, phase II trial (TORCH-C).

Abstract

147 Background: The prognosis for locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4 stage remains poor, with high rate of recurrence and metastasis. Although neoadjuvant chemotherapy is recommended, tumor regression is often limited. Hypofractionated radiotherapy has demonstrated enhanced synergistic effects when combined with PD-1 inhibitors and chemotherapy in rectal cancer. TORCH-C is the first prospective study evaluating neoadjuvant short course radiotherapy (SCRT) combined with chemotherapy and a PD-1 inhibitor in patients with microsatellite stable or mismatch-repair proficient (MSS/pMMR) LACC. Methods: This is a prospective, multicenter, randomized phase II trial (NCT05732493). A total of 120 LACC (T4/bulky N+M0，pMMR/MSS) patients will be randomized to either a chemotherapy group or a radiotherapy group. The chemotherapy group receives 4 cycles of CAPOX. The radiotherapy group receives SCRT（25Gy in 5 fraction) and 4 cycles of the PD-1 inhibitor (serplulimab) combined with CAPOX. The radiotherapy target volume includes only the primary colon tumor and enlarged lymph nodes, without elective nodal irradiation. After neoadjuvant therapy, patients will be evaluated for radical colon resection. The primary endpoint is pathological complete response (pCR) rate. The secondary endpoints include tumor downstaging, R0 resection, 3-year disease free survival (DFS), 3-year overall survival (OS) , 3-year local recurrence-free survival and treatment-related toxicity. Results: As of August 31, 2025, 120 patients have been enrolled and randomized. Of these, 79 patients have completed neoadjuvant treatment and surgery (43 in the chemotherapy group, 36 in the radiotherapy group). All 79 patients achieved radical resection, with R0 resection rates of 95.3% (41/43) in the chemotherapy group (95.3%, 41/43), and 97.2% (35/36) in the radiotherapy group. The pCR rate (TRG 0) was 11.6% (5/43) in chemotherapy group and 47.2% (17/36) in the radiotherapy group. The most common grade 3-4 adverse event (AE) among patients completing neoadjuvant treatment was thrombocytopenia (15.3%, 15/98), including 5 cases of grade 4 thrombocytopenia. Conclusions: The combination of PD-1 inhibitor, SCRT, and chemotherapy shows promising efficacy and may significantly improve pCR rates in patients with MSS/pMMR high-risk LACC. This regimen may provide a new therapeutic option to achieve R0 resection and improve long-term survival. Clinical trial information: NCT05732493 .