Short-course radiotherapy combined with chemotherapy and PD-1 inhibitor in low-lying early rectal cancer: study protocol for a single-arm, multicentre, prospective, phase II trial (TORCH-E).

Introduction: Current standard treatment for patients with early rectal cancer is radical surgical resection. Although radical surgery provides effective local tumour control, it also increases the mortality risk and considerable adverse effects, including bowel, bladder, sexual dysfunction and loss of anal function, especially in patients with low-lying rectal cancer. Recent studies have shown promising synergistic effects of the combination of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and radiotherapy in improving tumour regression. For patients who reach a clinical complete response (cCR) after neoadjuvant therapy, a 'Watch & Wait' (W&W) approach can be adopted to preserve anorectal function and improve quality of life. Thus, this study aims to explore the efficacy and safety of radiotherapy combined with chemotherapy and PD-1 antibody in patients with low early rectal cancer.

Methods And Analysis: TORCH-E study is designed as a multicentre, prospective, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor in patients with cT1-3bN0M0 low rectal cancer. The trial was initiated in December 2022 and is currently recruiting patients, with an anticipated completion of participant enrolment by June of the following year. The enrolled 34 patients will receive SCRT (25 Gy/5 Fx), followed by four cycles of capecitabine plus oxaliplatin chemotherapy and PD-1 antibody (toripalimab) and finally receive surgery or the W&W strategy. The primary endpoint is the complete response (CR) rate, that is, the rate of pathological complete response (pCR) plus cCR. The secondary endpoints include organ preservation rate, 3-year local recurrence-free survival rate, 3-year disease-free survival rate, 3-year overall survival rate, grade 3-4 adverse effects rate and patients' quality of life.

Ethics And Dissemination: This trial has been approved by the Ethics Committee of Fudan University Shanghai Cancer Center. Trial results will be disseminated via peer-reviewed journals and conference presentations.

Trial Registration Number: NCT05555888 (ClinicalTrials.gov).