Can neoadjuvant chemoradiotherapy be omitted in cT2N+ and cT3 mid-rectal cancer: Protocol for a prospective, observational, non-inferiority trial (CANO)

BackgroundNeoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer. However, nCRT is associated with significant morbidity, impacting patients quality of life. Recent advancements in MRI-based risk stratification have raised the possibility of omitting nCRT in selected patients without compromising oncologic outcomes. This study aims to evaluate whether upfront TME alone achieves non-inferior 3-year disease-free survival compared to the standard approach of nCRT followed by TME in patients with cT2N+ and cT3Nx mid-rectal cancer without mesorectal fascia involvement. MethodsThe CANO trial is a prospective, multicenter, observational non-inferiority study involving 1992 patients across Turkiye. Eligible patients will be classified into two groups: those undergoing direct TME and those receiving nCRT followed by TME. The primary endpoint is 3-year disease-free survival (DFS), with secondary outcomes including 5-year DFS, overall survival, local recurrence rates, and quality of life assessments using validated questionnaires. Data will be prospectively collected and monitored by the steering committee with predefined interim analyses. DiscussionThe CANO trial addresses the ongoing debate regarding selective omission of nCRT in low-risk mid-rectal cancer. By leveraging MRI-based risk stratification and a collaborative national network, the study aims to provide high-quality evidence supporting a more personalized treatment approach. The findings have the potential to reduce treatment-related morbidity without compromising oncologic safety, contributing to the refinement of current guidelines. Trial registrationNCT06823297 [ClinicalTrials.gov] [registered before starting inclusion; Version 3, 03.02.2025].