2961 - Short-Course Radiotherapy Combined with Chemotherapy and PD-1 Inhibitor in Proficient Mismatch Repair or Microsatellite Stable (pMMR/MSS) Low-Lying Early Rectal Cancer: Preliminary Findings from a Pro

Y. Chen¹, Y. Wang¹, H. Zhang¹, J. Wan¹, L. Shen¹, Y. WANG¹, W. Yang¹, M. Zhou¹, R. Wu¹, S. Zhou¹, Y. Bai², D. Zhou², J. Li³, S. Cai⁴, X. Li⁴, F. Xia¹, and Z. Zhang¹; ¹Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, ²Department of Radiation Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, China, Shanghai, China, ³Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China, ⁴Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

Purpose/Objective(s): Radical surgery is the conventional treatment for stage I-II rectal cancer (cT1-3bN0M0). However, this approach may increase mortality and anal dysfunction, particularly in low-lying rectal cancer patients. Emerging research suggests that neoadjuvant radiotherapy combined with immunotherapy enhance tumor regression in pMMR/MSS locally advanced rectal cancer and could enable organ preservation via a "Watch and Wait" (WW) strategy in patients who achieve a clinical complete response (cCR). Therefore, this study investigates the efficacy and safety of integrating radiotherapy, chemotherapy, and PD-1 inhibitor in early-stage, low-lying pMMR/MSS rectal cancer. Materials/

Methods: TORCH-E study (NCT05555888) is designed as a prospective, multi-center, phase II trial. Thirty-four patients with cT1-3bN0M0 rectal adenocarcinoma proven pMMR/MSS and located =5cm from the anal verge will receive short-course radiotherapy (25 Gy/5 Fx) followed by four cycles of immunochemotherapy with CAPOX and the PD-1 inhibitor Toripalimab. Tumor restaging will be performed within 4 weeks after completion of neoadjuvant treatment. A WW option can be applied to patients achieving cCR while surgery was recommended for those who failed to achieve cCR. The primary endpoint is complete response (CR) which includes pathological complete response after surgery and cCR if WW was applicable. The secondary endpoints include compliance, the grade 3-4 acute adverse effects (AE) rate, surgical morbidity, 3-year disease free survival (DFS) rate, etc.
Results: Up to February 2024, 20 patients have completed neoadjuvant treatment with a high compliance rate (95%). The median age was 61 years and 85% (17/20) patients had T3 disease defined by rectal magnetic resonance imaging, The median distance from anal verge was 3 (range, 1-5) cm. Among 20 evaluable patients, 10 patients achieved cCR and adopted WW. Other 10 patients underwent surgery, within which 4 had local excision and showed no residual tumor cells (ypT0), 6 received total mesorectal excision and 3 confirmed no residual tumor cells from the primary tumor and lymph nodes (ypT0N0, TRG0). Thus, the total CR rate was 85% (17/20). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 6 patients, including 5 (25%) thrombocytopenia and 1(5%) leukopenia, and there were no treatment-related deaths.
Conclusion: The innovative therapeutic approach combining PD-1 monotherapy with SCRT and chemotherapy has achieved a remarkable CR rate of 85%, which may offer a promising option for pMMR/MSS, low-lying early rectal cancer patients to achieve organ preservation.