Pathway Of Low Anterior Resection syndrome relief after Surgery (POLARiS) feasibility trial protocol: a multicentre, feasibility cohort study with embedded randomised control trial to compare sacral neuromodulation and transanal irrigation to optimised conservative management in the management of major low anterior resection syndrome following rectal cancer treatment.

INTRODUCTION: Rectal cancer is common with a 60% 5-year survival rate. Treatment usually involves surgery with or without neoadjuvant chemoradiotherapy or adjuvant chemotherapy. Sphincter saving curative treatment can result in debilitating changes to bowel function known as low anterior resection syndrome (LARS). There are currently no clear guidelines on the management of LARS with only limited evidence for different treatment modalities. METHODS AND ANALYSIS: Patients who have undergone an anterior resection for rectal cancer in the last 10 years will be approached for the study. The feasibility trial will take place in four centres with a 9-month recruitment window and 12 months follow-up period. The primary objective is to assess the feasibility of recruitment to the POLARiS trial which will be achieved through assessment of recruitment, retainment and follow-up rates as well as the prevalence of major LARS.Feasibility outcomes will be analysed descriptively through the estimation of proportions with confidence intervals. Longitudinal patient reported outcome measures will be analysed according to scoring manuals and presented descriptively with reporting graphically over time. ETHICS AND DISSEMINATION: Ethical approval has been granted by Wales REC1; Reference 22/WA/0025. The feasibility study is in the process of set up. The results of the feasibility trial will feed into the design of an expanded, international trial. TRIAL REGISTRATION NUMBER: CT05319054.

Liver resection surgery compared with thermal ablation in high surgical risk patients with colorectal liver metastases: the LAVA international RCT.

BACKGROUND: Although surgical resection has been considered the only curative option for colorectal liver metastases, thermal ablation has recently been suggested as an alternative curative treatment. There have been no adequately powered trials comparing surgery with thermal ablation. OBJECTIVES: Main objective - to compare the clinical effectiveness and cost-effectiveness of thermal ablation versus liver resection surgery in high surgical risk patients who would be eligible for liver resection. Pilot study objectives - to assess the feasibility of recruitment (through qualitative study), to assess the quality of ablations and liver resection surgery to determine acceptable standards for the main trial and to centrally review the reporting of computed tomography scan findings relating to ablation and outcomes and recurrence rate in both arms. DESIGN: A prospective, international (UK and the Netherlands), multicentre, open, pragmatic, parallel-group, randomised controlled non-inferiority trial with a 1-year internal pilot study. SETTING: Tertiary liver, pancreatic and gallbladder (hepatopancreatobiliary) centres in the UK and the Netherlands. PARTICIPANTS: Adults with a specialist multidisciplinary team diagnosis of colorectal liver metastases who are at high surgical risk because of their age, comorbidities or tumour burden and who would be suitable for liver resection or thermal ablation. INTERVENTIONS: Thermal ablation conducted as per local policy (but centres were encouraged to recruit within Cardiovascular and Interventional Radiological Society of Europe guidelines) versus surgical liver resection performed as per centre protocol. MAIN OUTCOME MEASURES: Pilot study - patients' and clinicians' acceptability of the trial to assist in optimisation of recruitment. Primary outcome - disease-free survival at 2 years post randomisation. Secondary outcomes - overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, and disease-free survival measured from end of intervention. It was planned that 5-year survival data would be documented through record linkage. Randomisation was performed by minimisation incorporating a random element, and this was a non-blinded study. RESULTS: In the pilot study over 1 year, a total of 366 patients with colorectal liver metastases were screened and 59 were considered eligible. Only nine participants were randomised. The trial was stopped early and none of the planned statistical analyses was performed. The key issues inhibiting recruitment included fewer than anticipated patients eligible for both treatments, misconceptions about the eligibility criteria for the trial, surgeons' preference for one of the treatments ('lack of clinical equipoise' among some of the surgeons in the centre) with unconscious bias towards surgery, patients' preference for one of the treatments, and lack of dedicated research nurses for the trial. CONCLUSIONS: Recruitment feasibility was not demonstrated during the pilot stage of the trial; therefore, the trial closed early. In future, comparisons involving two very different treatments may benefit from an initial feasibility study or a longer period of internal pilot study to resolve these difficulties. Sufficient time should be allowed to set up arrangements through National Institute for Health Research (NIHR) Research Networks. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52040363. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 21. See the NIHR Journals Library website for further project information.

In about 50% of people with bowel cancer, cancer spreads to the liver (colorectal liver metastases) within 5 years of detection and treatment. Liver resection (i.e. surgical removal of a portion of the liver) is the standard treatment in people below 70 years of age who are otherwise well, provided that the liver cancer is confined to a limited part of the liver. Such patients are considered 'low-risk' patients. Older patients and those with major medical problems or extensive cancers are considered 'high-risk' patients, as they are at a higher risk of developing complications following liver resection. Thermal ablation destroys the liver cancers using a needle that heats the cancer deposits until they are destroyed. There is significant uncertainty as to whether or not ablation can offer equivalent survival compared with surgery for 'high-risk' patients. We planned and conducted a randomised controlled trial comparing ablation with surgery to resolve this uncertainty. In this trial, some patients received ablation and others received surgery. The treatment was allocated at random with neither patients nor the study organisers choosing the treatment. The trial had an internal pilot (i.e. a smaller version of the full trial to resolve any 'teething problems' and ensure that a sufficient number of participants can be included in the full trial). Only nine patients were recruited in the 1-year internal pilot, compared with the anticipated recruitment of 45 patients. Therefore, the trial closed early as a result of poor recruitment, and the uncertainty about the best treatment for high-risk patients with colorectal liver metastases continues. The main reasons for the poor recruitment included fewer than anticipated eligible participants, clinicians' unconscious bias towards surgery, and patients' preference for one treatment or the other. In the future, comparisons involving two very different treatments may benefit from a feasibility study or a longer period of pilot study to resolve any difficulties.

SaFaRI: sacral nerve stimulation versus the FENIX magnetic sphincter augmentation for adult faecal incontinence: a randomised investigation.

PURPOSE: Faecal incontinence is a physically, psychologically and socially disabling condition. NICE guidance (2007) recommends surgical intervention, including sacral nerve stimulation (SNS), after failed conservative therapies. The FENIX magnetic sphincter augmentation (MSA) device is a novel continence device consisting of a flexible band of interlinked titanium beads with magnetic cores that is placed around the anal canal to augment anal sphincter tone through passive attraction of the beads. Preliminary studies suggest the FENIX MSA is safe, but efficacy data is limited. Rigorous evaluation is required prior to widespread adoption. METHOD AND DESIGN: The SaFaRI trial is a National Institute of Health Research (NIHR) Health Technology Assessment (HTA)-funded UK multi-site, parallel group, randomised controlled, unblinded trial that will investigate the use of the FENIX MSA, as compared to SNS, for adult faecal incontinence resistant to conservative management. Twenty sites across the UK, experienced in the treatment of faecal incontinence, will recruit 350 patients randomised equally to receive either SNS or FENIX MSA. Participants will be followed-up at 2 weeks post-surgery and at 6, 12 and 18 months post-randomisation. The primary endpoint is success, as defined by device in use and ≥50 % improvement in the Cleveland Clinic Incontinence Score (CCIS) at 18 months post-randomisation. Secondary endpoints include complications, quality of life and cost effectiveness. DISCUSSION: SaFaRI will rigorously evaluate a new technology for faecal incontinence, the FENIX™ MSA, allowing its safe and controlled introduction into current clinical practice. These results will inform the future surgical management of adult faecal incontinence.