Award Title: Pathway Of Low Anterior Resection syndrome relief after Surgery (POLARiS) trial
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Plain English Summary  max 3500 (remaining 189 characters) _x000D_
14,000 cases of rectal cancer are diagnosed in the UK per year. The treatment for advanced rectal cancer is often radiotherapy+/-chemotherapy treatment followed by surgery. This provides good outcomes, with the cancer returning in less than 10% of people. However, the surgery can cause significant long-lasting problems, including problems with bowel, sexual and urinary function. Low anterior resection syndrome (LARS) is a collection of symptoms that people who have undergone a partial or total removal of the rectum may experience, including bowel incontinence or leakage, frequency or urgency of stools, loose stools and incomplete bowel emptying. These symptoms can have a considerable negative impact on patient quality of life and daily functioning. As a result, there is a need to focus efforts on survivorship._x000D_
LARS symptoms are present in 75% of the patients up to 12 months after surgery and remain in up to 50% of patients for more than 10 years with a major impact on quality of life. There is little evidence to support treatment options for patients with LARS. Despite more acceptance of LARS amongst clinicians, with increased subspecialisation of surgeons and poor reporting of LARS, many centres do not have a clear management pathway and/or are unaware of the treatments available. _x000D_
Transanal irrigation (TAI) is a method of managing conditions such as bowel incontinence or constipation. It involves introducing water through the anus to flush faeces (poo) from the bowel. Sacral Neuromodulation (SNM) involves a small battery powered unit being implanted into the lower back. This is connected to electrodes which rest on the nerves in the lower spine. The device continuously sends electrical impulses to the nerves and muscles that control the lower bowel (rectum and anus)._x000D_
These two treatment options may improve quality of life for patients with LARS, however supportive evidence is currently lacking. The POLARiS trial will investigate the clinical and cost benefit of two treatments for patients with major LARS who have previously undergone standard non-surgical treatment without improvement. Patients who are not randomised to SNM or TAI will be offered optimised medical management. _x000D_
The study will monitor the bowel function and quality of life in patients who have undergone rectal cancer surgery in the hospitals involved within the last 10 years of the trial commencing. Those patients found to have poor bowel function (major LARS) will be randomised to one of the treatment options and followed up for 2 years after randomisation. _x000D_
The results of the study will be presented at conferences raising awareness of effective treatment options to clinicians, as well as through publication in peer reviewed journals. Patient material will be developed as part of the output of POLARiS which will offer self-management strategies and explanation of treatment options for patients with LARS. The findings of the study will be highlighted through social media to patient groups and relevant charities. This will inform patients and the public that LARS is treatable and which treatment options are potentially available. Patients who have participated in the study will receive a patient report at the end, with clear outlines of the findings.

Lay Abstract: 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. _x000D_
Aims and objectives _x000D_
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)?” _x000D_
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. _x000D_
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)._x000D_
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.  _x000D_
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.  _x000D_
Interventions: Sacral neuromodulation or Transanal irrigation. _x000D_
Comparator: Optimised Conservative Management _x000D_
Outcomes: Primary; LARS score over 24-months; Secondary – quality of life, safety, cost-effectiveness, compliance, acceptability, fidelity. _x000D_
The RCT within the cohort has three 1:1 randomisation options dependent on patient and site eligibility: _x000D_
1) SNM vs OCM, for patients who would not be eligible to receive TAI _x000D_
2) TAI vs OCM, for patients who would not be eligible to receive SNM _x000D_
3) SNM vs TAI vs OCM for patients who are eligible to receive either SNM or TAI. _x000D_
Setting: 20 UK, European and Australian secondary care sites utilising existing networks from the IntAct trial and Australian ALaCaRT._x000D_
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.  _x000D_
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.

Research Activity Codes: 6.3 MEDICAL DEVICES
Health Categories: CANCER AND NEOPLASMS;ORAL AND GASTROINTESTINAL