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

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.