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/III 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 oncological 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.