What does this research mean for the field?

Neoadjuvant CAPOX plus a PD-1 inhibitor achieves a 36.9% complete response rate in pMMR locally advanced rectal cancer, which is further enhanced to 61.1% with the addition of short-course radiotherapy. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This trial aims to evaluate the efficacy and functional outcomes of two total neoadjuvant therapy approaches in patients with proficient mismatch repair locally advanced rectal cancer.

May 29, 2026

Immunotherapy-based total neoadjuvant therapy with or without short-course radiotherapy for locally advanced rectal cancer: Preliminary results of TORCH-iTNT.

Key Points

This trial aims to evaluate the efficacy and functional outcomes of two total neoadjuvant therapy approaches in patients with proficient mismatch repair locally advanced rectal cancer.
Prospective, multicenter, randomized phase II study involving 192 patients with proficient mismatch repair locally advanced rectal cancer.
Participants were randomly assigned to either CAPOX plus PD-1 inhibitor or SCRT followed by CAPOX plus PD-1 inhibitor.
Primary endpoint was complete response rate, secondary endpoints included organ preservation and adverse effects.
Overall complete response rates were 36.9% in Group A and 61.1% in Group B.
Pathological complete response was observed in 35.2% of surgeries in Group A and 44.9% in Group B.
The most common high-grade toxicity was thrombocytopenia, with rates of 12.3% in Group A and 12.5% in Group B.

Abstract

3644 Background: In patients with proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC), the integration of PD-1 inhibitor into total neoadjuvant chemoradiotherapy (iTNT) has demonstrated promising potential to enhance complete response (CR) rates and facilitate organ preservation. However, the combined use of radiotherapy and surgical intervention frequently leads to increased functional impairment relative to either modality administered independently. Concurrently, the combination of chemotherapy and PD-1 inhibitor has been shown to promote tumor downstaging, thereby enabling sphincter-preserving surgery while mitigating radiation-induced injury. This trial evaluates oncological efficacy and functional outcomes of two iTNT regimens: CAPOX plus PD-1 inhibitor with or without SCRT in neoadjuvant treatment of pMMR LARC patients. Methods: The TORCH-iTNT trial (NCT06281405) is a prospective, multicenter, randomized phase II study involving 192 patients with pMMR LARC (T3-4/N+M0). Participants were randomized into Group A (6 cycles of CAPOX plus toripalimab) or Group B (SCRT 25Gy/5Fx followed by 6 cycles of CAPOX plus toripalimab). Patients achieving clinical complete response (cCR) were offered a watch-and-wait (W Group B: 72). Baseline characteristics were balanced, with 97.1% (133/137) exhibiting at least one high-risk feature: lower tumor location (≤5cm), cT4, cN2, MRF+, or EMVI+. In Group A, 5 patients achieved cCR and adopted W Group B: 12.5%). Conclusions: This study is the first comparative analysis of two iTNT regimens in LARC. Unprecedentedly, neoadjuvant CAPOX plus PD-1 inhibitor achieved a promising CR rate in pMMR LARC, and this CR rate can be further enhanced with the addition of SCRT prior to immunochemotherapy. Further follow-up is necessary to assess long-term efficacy and functional endpoints. Clinical trial information: NCT06281405 .

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