Title: The PARTIAL study – a randomised trial of the clinical and cost effectiveness of PARTIAL vs radical nephrectomy for clinically localised renal cell carcinoma
Funder: Department of Health and Social Care

Abstract: 1. BACKGROUND _x000D_ Each year over 13,000 people in the United Kingdom are diagnosed with a kidney cancer (7th commonest cancer). Historically, many patients presented late with symptoms from large cancerous growths and in individuals with a normal kidney on the unaffected side, the standard treatment was to remove the entire affected kidney. Nowadays, most kidney cancers are found at a much earlier stage when a scan is performed for an unrelated condition. These smaller cancers can either be treated by removing the entire affected kidney or just the portion of the kidney affected by the tumour. However removing just the kidney tumour is more difficult than taking the entire kidney out. Partial kidney removal comes with a slightly greater risk of inadvertently leaving some cancer behind requiring retreatment. Bleeding and urine leakage are also a risk with partial removal of the kidney, also possibly requiring further treatments. Nevertheless, partial kidney surgery remains attractive as these additional risks could be traded off with potential benefits from maintaining more kidney function. This may reduce the chances of developing kidney failure and requiring dialysis. Loss of kidney function is also associated with developing heart disease in the future and potentially dying from a heart attack or stroke. However, there are no high quality succesfully completed clinical trials comparing which approach is better. Despite the lack of good data surgery taking part of the kidney has been increasingly performed, as modern robot assisted key-hole approaches make it more accessible. _x000D_ _x000D_ 2. AIM_x000D_ In patients with kidney cancer and a normal kidney on the other side, we plan to conduct a clinical trial to answer the question of whether a partial removal of the kidney (partial nephrectomy) is better than removing the whole kidney (radical nephrectomy)?_x000D_ _x000D_ 3. DESIGN AND METHODS _x000D_ Everyone that takes part on our study will have an equal chance of either partial or total removal of the kidney. We will compare the two treatments in terms of their effect on how well the kidney(s) are working (through regular blood tests), quality of life, complication rates and survival. We will also compare the use of NHS resources. The study will recruit 420 patients from 30 hospitals spread across the UK and will investigate what happens to those treated in either way over 2 years. The study team brings together patients, clinicians and researchers to answer this question._x000D_ _x000D_ 4. PATIENT AND PUBLIC INVOLVEMENT_x000D_ Mr David di Mambro is leading our Patient and Public Involvement. He has lived experience of kidney cancer and surgery and, supported by our Patient Advisory Group (PAG) and Kidney Cancer UK (KCUK) charity, brings invaluable experience in guiding the co-production of this application. Our PPI group will provide advice about the conduct of the trial from a patient perspective and support the research team in development of patient-facing resources and activities to foster participant connectedness with the study._x000D_ _x000D_ 5. DISSEMINATION_x000D_ Results of the study will be distributed to patients and families affected with kidney cancer through bespoke plain English summaries generated in conjunction with our PPI group through lay media outlets, social media and charity run patient portals (e.g. KUCK, CRUK, BAUS). Scientific output will be through academic conferences and publications.

Lay abstract: RESEARCH QUESTION_x000D_ Does partial nephrectomy (PN) for intermediate sized (stage T1b) & deep-seated small (T1a) tumours result in better outcomes than radical nephrectomy (RN) in patients with localised primary RCC & normal contralateral kidney?_x000D_ _x000D_ AIMS/OBJECTIVES_x000D_ Aim: Characterise the trade-off of the potential benefits, harms and costs over a 2-year follow-up in comparing PN & RN_x000D_ _x000D_ 1. Primary objectives: Describe benefits (renal function preservation) & harms (surgical complications)_x000D_ 2. Secondary objectives: Compare (i) HRQoL, (ii) cost & cost-effectiveness (capturing length of stay), (iii) quality of recovery, (iv) positive surgical margin rates (& retreatment), (v) survival (RFS/OS), (vi) cardiovascular events (inc. stroke), (vii) chronic kidney disease (CKD), (viii) operative conversions & (ix) patient acceptability _x000D_ 3. Long-term outcomes: (i) consent for separately funded follow-up allowing correlations of renal preservation with cardiovascular events, survival & end-stage kidney disease (ESKD) at 5–10 years. (ii) Establish a cohort of clinical data, urine, blood & tumour specimens for future studies (separately funded)_x000D_ _x000D_ METHODS_x000D_ Design: Two-arm multicentre pragmatic superiority RCT (1:1) of PN vs RN_x000D_ Health technology: Minimal invasive surgery for both RN & PN (reflecting normal national practice)_x000D_ Target population (in 30 NHS secondary care sites):_x000D_ 1. Inclusion criteria: localised primary RCC on routine cross-sectional imaging, where the multidisciplinary team agrees both PN & RN are suitable, primariliy T1b (4-7cm) & selected T1a (<4cm) tumours with hilar & endophytic growth (surveyed equipoise & willingness to recruit)_x000D_ 2. Exclusion criteria: Single functioning kidney, multiple renal tumours, reduced eGRF (<60), age <18_x000D_ Outcome measures:_x000D_ 1. Primary outcomes: (i) gains due to preserving renal tissue (eGFR at baseline, 3, 6, 12, 18, & 24 months) & (ii) harms captured by Comprehensive Complication Index (CCI) over the peri-operative period (90 days)_x000D_ 2. Secondary outcomes: (i) HRQoL – EORTC QLQ-C30 & acute version of the SF-36, (ii) cost-effectiveness (QALY & costs), (iii) QoR-15 quality of recovery questionnaire (inc. length of stay), (iv) positive surgical margins, local recurrence, retreatment, (v) RFS & OS, (vi) cardiovascular events & stroke, (vii) progression to chronic kidney disease stages 3, 4, & 5 (end stage) by eGFR, (viii) operative conversion to RN, (ix) patient & clinician acceptability (an embedded evaluation of the recruitment process)_x000D_ 3. Long-term outcomes: (i) Cardiovascular events, survival (CSS/OS) & longitudinal eGFR measures to capture rates of ESKD at 5-10 years. (ii) Well-characterised cohort of patient tissue for future studies of biomarker for detection, surveillance, prognosis, & best treatment strategies_x000D_ _x000D_ SAMPLE SIZE_x000D_ 420 participants to get adequate precision around the confidence interval of the between-group difference in eGFR to show PN is at least 10 mL/min/1.73m2 better (inflated by 15% for attrition at 2-yrs)_x000D_ _x000D_ TIMELINES_x000D_ Study set up 1-6m, recruitment 7-30m (first 9m internal pilot), 2-yr follow up 31-54m, analysis & write up 55-60m_x000D_ _x000D_ IMPACT/DISSEMINATION_x000D_ Clinical results will be presented in high-impact journals & conferences. Lay summaries to disseminate to those patients who participated, and also to patient organisations (KCUK & TUF) websites & social media. We will inform policy makers shaping NHS practice, such as NICE, NHS England & international guideline writing committee

Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS