Can we Save the rectum by watchful waiting or TransAnal surgery following (chemo)Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR-TREC)? Protocol for the international, multicentre, rolling phase II/IIII partially randomized patient preference trial evaluating long-course concurrent chemoradiotherapy versus short-course radiotherapy organ preservation approaches

Aim: Organ-saving treatment for early-stage rectal cancer can reduce patient-reported side effects compared to standard total mesorectal excision (TME) and preserve quality of life. An optimal strategy for achieving organ preservation and longer-term ontological outcomes are unknown; thus there is a need for high quality trials. Method: Can we Save the rectum by watchful waiting or TransAnal surgery following (chemo)Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR-TREC) is an international three-arm multicentre, partially randomized controlled trial incorporating an external pilot. In phase III, patients with cT1-3b N0 tumours, <= 40 mm in diameter, who prefer organ preservation are randomized 1:1 between mesorectal long-course chemoradiation versus mesorectal short-course radiotherapy, with selective transanal microsurgery. Patients preferring radical surgery receive TME. STAR-TREC aims to recruit 380 patients to organ preservation and 120 to TME surgery. The primary outcome is the rate of organ preservation at 30 months. Secondary clinician-reported outcomes include acute treatment-related toxicity, rate of non-operative management, non-regrowth pelvic tumour control at 36 months, non-regrowth disease-free survival at 36 months and overall survival at 60 months, and patient-reported toxicity, health-related quality of life at baseline, 12 and 24 months. Exploratory biomarker research uses circulating tumour DNA to predict response and relapse. Discussion: STAR-TREC will prospectively evaluate contrasting therapeutic strategies and implement new measures including a smaller mesorectal target volume, two-step response assessment and non-operative management for complete response. The trial will yield important information to guide routine management of patients with early-stage rectal cancer.