Title: CRUK/19/005 - STARTREC Phase 3: Saving the rectum by watchful waiting or TransAnal surgery following (chemo)Radiotherapy versus Total mesorectal excision for early Rectal Cancer
Funder: Cancer Research UK

Abstract: Background: Bowel cancer is the second most common tumour with 41,000 new UK cases annually, 447,000 across Europe and 1.36M worldwide; of which one third are located in the rectum. Bowel screening has greatly increased detection of early stage rectal cancer, yet surgery to remove the rectum remains standard treatment; despite causing substantial morbidity, occasional mortality and significant impairment to quality of life. A key research question is whether patients with early-stage rectal cancer can safely avoid radical surgery through an organ preservation strategy that utilises (chemo)radiotherapy and selective transanal local excision? The optimal organ preservation approach remains to be defined, published rates vary considerably and toxicity has prohibited widespread adoption. The STAR-TREC feasibility study introduced novel organ preservation strategies, designed to optimise organ preservation rates and substantially reduce treatment related toxicity. Key themes were (i) evaluation of contrasting (chemo)radiotherapy schedules, (ii) smaller radiotherapy fields, risk adapted for early cancers, (iii) standardised assessment of treatment response over a longer 5-month period, (iv) non-operative management of complete response (no evidence of residual tumour) and (v) delayed transanal microsurgery for partial response to reduce subsequent conversion to radical surgery based upon incomplete downstaging. Aims: To define the optimal organ preserving strategy for early stage rectal cancer in terms of effectiveness, toxicity and HRQoL? We shall evaluate two contrasting treatment schedules: (i) mesorectal chemoradiation (CRT) and (ii) mesorectal short course radiotherapy (SCRT). Biomarker research will investigate the potential of genomic markers in blood (ctDNA), associated with persistence of tumour tissue to direct surgical intervention. We shall record how toxicity, HRQL and patient satisfaction differ following organ preservation versus standard surgery? Methods: STAR-TREC is a multicentre, international study coordinated from Birmingham UK with hubs in the Netherlands and Denmark. Eligible patients have biopsy proven, early stage rectal cancer (mrT1-T3bV0N0M0), 4cm or less in diameter. Individuals indicate their preference for (a) an organ preserving approach or (b) standard surgery. Those who select organ preservation randomise 1:1 between (i) mesorectal CRT(25 x 2Gy + concurrent capecitabine) and selected local excision versus (ii) mesorectal SCRT(5 x 5Gy) and selected local excision. We plan to recruit 380 patients in total across the three countries to determine the best organ preserving strategy for patients with early stage rectal cancer. Results: If proven safe and effective the superior organ preserving strategy will be proposed as first line treatment of early stage rectal cancer through national and international bowel cancer guidelines.


Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS