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, with economic evaluation, process evaluation and qualitative sub-study, to explore the natural history of Low Anterior Resection Syndrome (LARS) and compare trans-anal irrigation and sacral neuromodulation to optimised conservative management for people with major LARS following a high or low anterior resection for colorectal cancer
Authors: Croft Julie , Farrow Emily , Coxon-Meggy Alexandra Harriet , Gordon Katie , Corrigan Neil , Mather Hannah , Stocken Deborah , Dale Megan , Chong Huey Yi , White Judith , Knight Laura , Meggy Alun , Lloydwin Christina , Tan Betty , Douglas Ashley , Powell Ralph , Hepburn Julie , Jayne David , Torkington Jared , Warwick Andrea , Ng Kheng-Seong , Wilson Kate , Knowles Charles , Quyn Aaron , Cornish Julie 
Published: August 2024

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.

POLARiS is a prospective, international, open-label, multi-arm, phase 3 randomised superiority trial within a cohort (TWiCs design), with internal pilot phase, qualitative sub-study, process evaluation, and economic evaluation. Approximately 1500 adult participants from UK hospitals and 500 from Australian hospitals who have undergone a high or low anterior resection for colorectal cancer in the last 10 years will be recruited into the cohort. 600 participants from the UK and 200 participants from Australia, with major LARS symptoms, defined as a LARS score of ≥30, will be recruited to the randomised controlled trial (RCT) element. Participants entering the RCT will be randomised between OCM, TAI or SNM, all with equal allocation ratios.

Cohort and RCT participants will be followed up for a 24-month period, completing a series of questionnaires measuring LARS symptoms and QoL, 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 up to 24 months post registration/randomisation. 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. Secondary outcomes include health-related QoL, adverse events, treatment compliance and cost effectiveness (up to 24 months post registration/randomisation)

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

Strengths and Limitations

The trial is pragmatically designed to optimise and assess recruitment and retainment.

This trial includes an economic evaluation of treatment options specific to both the UK and Australia.

Lay representatives with personal experience of bowel cancer and LARS have contributed throughout the trial design and ongoing Trial Management Group meetings.

There are recognised potential limitations to the LARS score, including limited sensitivity to detect real time change in response to treatment. Additional outcome measures of Quality of Life and a new LARS Patient Reported Outcome Measure (PROM) are being collected to give a more nuanced picture of treatment response.