Organ preservation via immunotherapy-based total neoadjuvant therapy in early low rectal cancer (TORCH-E): a multicenter, open-label, single-arm, phase 2 study.

Abstract

PURPOSE Organ preservation (OP) can be preferred in low-lying rectal cancer to reduce morbidity from radical surgery. Immunotherapy-based total neoadjuvant therapy (iTNT) showed remarkable tumor regression and facilitated OP in locally advanced rectal cancer. This study evaluated the efficacy and safety of iTNT, comprising short-course radiotherapy (SCRT) followed by CAPOX and Toripalimab, in enabling OP for early low rectal cancer. PATIENTS AND METHODS TORCH-E was a multicenter, single-arm phase 2 trial enrolling patients with T2-3bN0 rectal adenocarcinoma ≤5 cm from anal verge. Patients received SCRT (25Gy/5Fx) followed by four cycles of CAPOX plus Toripalimab. Good responders were eligible for watch-and-wait (WW) or local excision (LE), total mesorectal excision (TME) was recommended for poor responders or those with high-risk features post-LE. The primary endpoint was complete response (CR), including clinical complete response (cCR) with WW and pathological CR (pCR). Secondary endpoints included OP rate, adverse effects, and quality of life. RESULTS From December 2022 to March 2024, 33 patients were enrolled, with 75.8% staged as T3. After iTNT, 16 patients achieved cCR and adopted WW. pCR was observed in 8/8 LE and 5/9 TME patients. The most common grade 3-4 adverse event was thrombocytopenia (27.3%). After a median follow-up of 24.1 months, four local regrowth and one metastatic recurrence occurred. Total CR rate was 72.7%, and OP rate was 60.6%. CONCLUSIONS As an exploratory trial, TORCH-E demonstrated a promising iTNT approach achieving high CR rate, enabling OP through WW and selective LE in early low rectal cancer, warranting subsequent randomized validation.