Pathway of Low Anterior Resection Syndrome (LARS) Relief After Surgery (POLARiS) Trial Protocol. A prospective, international, open-label, multi-arm, phase 3 randomised superiority trial within a cohort to explore the natural history of LARS and compare the trans-anal irrigation and sacral neuromodulation to optimised conservative management for people with major LARS.

Abstract

Introduction As a result of improving survival rates, the adverse consequences of rectal cancer surgery are becoming increasingly recognised. Low Anterior Resection Syndrome (LARS) is one such consequence and describes a constellation of bowel symptoms after rectal cancer surgery which includes urgency, faecal incontinence, stool clustering and incomplete evacuation. LARS has a significant adverse impact on Quality-of-Life (QoL) and symptoms are present in up to 75% of patients in the first year after surgery. Despite this, little is known about the natural history and there is poor evidence to support current treatment options. Methods and Analysis The objectives of POLARiS are to explore the natural history of LARS and to evaluate the clinical and cost-effectiveness of trans-anal irrigation (TAI) or sacral neural modulation (SNM) compared to optimised conservative management (OCM) for people with major LARS. All patients who have had an anterior resection in the last 10 years who meet the eligibility criteria will be invited to participate in the cohort. Patients identified as having a major LARS score (LARS score ≥30) and who meet the eligibility criteria will be invited to take part in the randomised controlled trial (RCT). Cohort and RCT participants will be followed up for a 24-month period, and will complete a series of questionnaires measuring LARS symptoms and quality-of-life, as well as clinical review for those in the RCT. A process evaluation, qualitative sub-study and economic evaluation will also be conducted. The primary outcome measure of the POLARiS cohort and RCT is the LARS score at 24 months. Analyses of the RCT will be conducted on an intention-to-treat basis. Comparative effectiveness analyses for each endpoint will consist of two pairwise treatment comparisons: TAI vs OCM and SNM vs OCM. Ethics and Dissemination Ethical approval has been granted by Wales REC 4 (reference: 23/WA/0171) in the UK and Sydney Local Health District HREC (reference: 2023/ETH00749) in Australia. The results of this trial will be disseminated to participants upon request and published on completion of the trial in a peer-reviewed journal and at international conferences Trial Registration Number ISRCTN12834598 Registered 04/08/2023 ACTRN12623001166662 Registered 10/11/2023