Title: A feasibility study of a cohort embedded randomised control trial comparing NEphron Sparing Treatment (NEST) for small renal masses.
Funder: Department of Health and Social Care

Abstract: Research Question: Is a novel cohort embedded RCT in kidney cancer patients feasible to deliver for a full scale trial when a recruitment intervention is included? Background: Kidney cancer affects 12,500 patients every year in the UK and is predicted to increase 26% by 2035. The majority of kidney cancers are incidental findings, and half are less than 4cm in size, termed small renal mass (SRM). SRM are usually treated by robot assisted partial nephrectomy (RPN), a complex surgical procedure which is associated with an overall complication rate of around 28% and major complication rate of around 5%. Cryoablation (CRO) provides equivalent oncological control and also preserves renal function when used for treatment of SRMs. CRO is performed percutaneously, has an overall complication rate of 12%, and is currently offered to elderly or high surgical risk patients. There are no RCTs comparing CRO versus RPN. A feasibility trial will help determine whether a full-scale trial is possible. Aims and objectives: The aim of the feasibility trial is to determine the ability to recruit patients (recruitment rate) and the ability to retain patients to collect data (retention rate). The objective would be to inform the design, sample size and outcome measures for a subsequent large multicentre prospective RCT trial. Methods: An innovative cohort embedded RCT study design will be used to compare cryotherapy and partial nephrectomy (NEphron Sparing Treatment [NEST]) in small renal masses. Standard surgical RCTs have been notoriously challenging to deliver. Cohort embedded RCT designs have been used successfully in chronic obstructive pulmonary disease and rectal cancer trials and entails a two-stage consent process. The first stage consent allows the creation of an observational cohort of patients who consent to: future randomised invitation for new interventions and tests long term follow up complete questionnaires biobanking A proportion of patients that are eligible for the intervention are then randomly selected from the cohort and invited to consider the intervention (second stage/consent), those that are not selected form the control arm and receive the usual care. Proven recruitment intervention techniques including in-depth qualitative analysis of the recruitment pathway will be incorporated into the trial and together with the expertise of the surgical trials unit will identify and pre-empt any challenges to recruitment to optimise deliverability. Timelines for delivery: The study is scheduled to take 36 months: three months for preparatory work, 24 months recruitment of patients, 6 months for completion of follow-up of patients, and three months for analysis and final report. Anticipated impact and dissemination: The trial has the potential to inform the design of a definitive multicentre RCT that could make a major change to clinical practice in the treatment of small renal cancers both in the UK and globally. We will disseminate the findings at national conferences, peer-reviewed journals, patient information websites such as kidney cancer UK charity and the Royal Free charity, and links from the trial registry.

Lay abstract: Background to the research: There are 12,500 new cases of kidney cancer every year in the UK and it is predicted that this will rise to 16,000 by 2035. The majority of kidney cancers are detected by chance, on scans being performed for other purposes. The standard treatment for small kidney cancers, is surgical removal of the cancer while leaving normal kidney behind (partial nephrectomy). However, this is a complex procedure and 1 in 20 patients develop major complications such as leakage of urine into the abdomen, bleeding and bowel injury. An alternative treatment option is cryoablation, which involves killing cancer cells by freezing. It has less complications, faster recovery and gives equally good results. Currently, cryoablation is mainly offered to elderly patients or patients with significant medical problems. It is not clear if it can also benefit other patients. A clinical trial comparing the two options may answer this. We want to see if patients are willing to be involved in such a trial by conducting a feasibility study first. Aims of the research: To see whether patients with small renal cancers will take part in a study to compare cancer treatment by cryoablation with partial nephrectomy. Design and methods used: There are two stages to this study. The first stage is to invite all patients with small kidney cancers for permission for: long term follow up completion of questionnaires to donate blood, urine and tumour samples for future invitation for new interventions or tests that they may be suitable for. We aim to recruit 200 patients in this stage. The second stage is to invite patients with tumours that are suitable for either partial nephrectomy or cryoablation to consider cryoablation. We aim to recruit 50 patients to this part of the study. We will also conduct interviews with patients to understand the reasons why some patients may or may not want to take part in each stage of the trial. For example, whether the information provided is clear enough. Patient and public involvement: An online survey with Kidney Cancer UK (KCUK) involving ninety-nine patients demonstrated unanimous support and need for such a study. Our patient representatives helped draft the study protocol, patient information sheets and consent forms for the ethics application. They will represent patient views at the trial steering meetings, advise on the types of questions asked in the patient interviews, focus groups, the design of the full trial, and the reporting and dissemination of study findings. Dissemination: The results will be presented at national and international clinical meetings, published in high impact medical journals and communicated to the kidney cancer community through KCUK patient education days, social media and the KCUK and Royal Free Hospital websites.

Research activity codes: 6.4 SURGERY
Health categories: RENAL AND UROGENITAL;CANCER AND NEOPLASMS