Pathway Of Low Anterior Resection syndrome relief after Surgery (POLARiS) trial

Background: 14,000 UK patients are diagnosed with rectal cancer/annum. 52% will undergo major resectional surgery. LARS is a constellation of bowel symptoms described after rectal cancer surgery and includes urgency, faecal incontinence, stool clustering and incomplete evacuation leading to a significant adverse impact on quality of life (QoL). LARS symptoms are present in up to 75% of the patients 12 months after surgery and may persist in 25%. There is little evidence to inform choice of management and this was highlighted as a priority research question by NICE in 2020. Without greater evidence on cost effective treatments for LARS, patients will have a wide variation in care, both through differences in awareness and in access to treatment. Aims and objectives Aim: to answer the following research question: “What is the clinical and cost-effectiveness of Transanal irrigation (TAI) or Sacral neuromodulation (SNM) versus optimised conservative management (OCM) for people with major LARS (low anterior resection syndrome)?” Primary Objective: To conduct an international superiority randomised controlled trial (RCT) within a longitudinal cohort study (TWiCs design) to compare patient reported symptoms and quality of life in patients after rectal surgery. Secondary Objectives: to compare safety, complications, clinical efficacy and cost-effectiveness of the randomised treatments; describe the natural trajectory of patient reported LARS systems and predictors of major LARS; describe patient and staff views on the study and its interventions (including acceptability, impact and implementation). Design: A prospective, international, open-label, multi-arm, phase 3, randomised superiority trial, embedded within a cohort (TWiCs), with internal pilot phase, qualitative sub-study and economic evaluation. Participants: 600 UK patients with major LARS from a cohort of patients undergoing an anterior resection for cancer. Additional international patients to increase power and worldwide impact will be recruited subject to funding. Interventions: Sacral neuromodulation or Transanal irrigation. Comparator: Optimised Conservative Management Outcomes: Primary; LARS score over 24-months; Secondary – quality of life, safety, cost-effectiveness, compliance, acceptability, fidelity. The RCT within the cohort has three 1:1 randomisation options dependent on patient and site eligibility: 1) SNM vs OCM, for patients who would not be eligible to receive TAI 2) TAI vs OCM, for patients who would not be eligible to receive SNM 3) SNM vs TAI vs OCM for patients who are eligible to receive either SNM or TAI. Setting: 20 UK, European and Australian secondary care sites utilising existing networks from the IntAct trial and Australian ALaCaRT. Timelines for delivery: 66 months:0-9month set-up;10-36months recruitment (incl. 12month pilot phase),37-60months follow-up;61-66months analysis and dissemination. Anticipated impact and dissemination: POLARiS will, for the first time, accurately describe the natural history of LARS over time, determine the best treatment options for patients with major LARS and standardise practice worldwide. Results will be disseminated through presentation, publication as well as social media. Patient educational material, including a short animation video, will be produced, along with infographics to showcase findings.