Active Surveillance vs. Adjuvant Chemoradiotherapy for Locally Resected Intermediate-Risk T1 Rectal Cancer — a randomized trial asking a critical question: does intermediate risk always justify additional treatment after local excision?
After local removal of early rectal cancer, some patients are found to have histopathological features associated with an increased risk of recurrence or lymph node involvement. Current practice often recommends adjuvant chemoradiotherapy.
Yet most patients in this group may not have lymph node involvement and may not benefit oncologically from additional treatment. At the same time, chemoradiotherapy carries a real risk of long-term bowel dysfunction and treatment-related harm. T-REX evaluates whether active surveillance could safely replace routine additional treatment in selected patients.
Local excision already represents an organ-preserving approach to early rectal cancer. The dilemma begins after the pathology report: intermediate-risk features are identified, and the next step is no longer straightforward.
For many patients, current practice leads to chemoradiotherapy in order to reduce recurrence risk. But only a minority are expected to have nodal disease. This raises a central clinical question: when does risk justify additional treatment, and when might that treatment become overtreatment?
After local excision of early rectal cancer, pathology may reveal intermediate-risk features. At that stage, the main question is no longer how to remove the tumour, but whether further treatment is truly necessary.
Only a minority of patients in this group are expected to have lymph node involvement. This means many may receive chemoradiotherapy without clear oncological benefit.
Chemoradiotherapy may reduce recurrence risk, but it is associated with important treatment-related morbidity, including major LARS, urgency, clustering, and long-term bowel dysfunction.
T-REX evaluates both oncological safety and treatment-related harm through dual co-primary endpoints, reflecting the real trade-offs faced by patients and clinicians.
Trial hypothesis: active surveillance may reduce severe treatment-related harm while maintaining acceptable oncological safety.
T-REX evaluates more than recurrence alone. Within ECOPOP, the trial also addresses quality of life, stoma formation, bowel function, healthcare costs, and carbon footprint. This allows comparison of the two strategies not only in terms of cancer outcomes, but also in terms of what they mean for daily life after treatment.
Multicentre, prospective, randomized, open-label, controlled trial.
480 patients (240 per arm) across multinational European sites, with 5 years of follow-up.
Disease-related treatment failure at 3 years, including cancer-specific death, non-salvageable locoregional recurrence, and distant metastases.
Composite severe treatment-related adverse events at 3 years, including stoma formation, major LARS, CTCAE grade ≥3 toxicity, and Clavien-Dindo ≥3b complications.
Estimated severe treatment-related adverse events: 15.2% with active surveillance versus 39.6% with adjuvant chemoradiotherapy.
T-REX is intended for patients with early rectal cancer after complete local excision, when pathology identifies intermediate-risk features and both management strategies remain under consideration. Eligibility is always assessed by the treating study team.
Final eligibility is always determined individually by the study team according to the full protocol and clinical assessment.
Patients are identified and referred through participating centres. Eligibility is assessed locally after pathology review and clinical staging, before any enrolment decision is made.
Clinical centres interested in joining T-REX, or physicians wishing to refer eligible patients, are welcome to contact the coordination team.
Clinical centres interested in joining T-REX, or physicians wishing to refer eligible patients, are welcome to contact the coordination team.
Contact the teamQuestions about participation or site referral?
Email:
ecopop@gumed.edu.pl
Location:
Medical University of Gdańsk