Active Cancer Digestion, Kidneys & Other Organs

The PARTIAL study – a randomised trial of the clinical and cost effectiveness of PARTIAL vs radical nephrectomy for clinically localised renal cell carcinoma

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Surgeons will test whether removing only the cancerous part of a kidney, rather than the whole organ, leads to better outcomes for patients with medium-sized or awkwardly positioned kidney tumours. The standard treatment for these patients is radical nephrectomy—removing the entire kidney. But many patients later develop chronic kidney disease or cardiovascular problems from living with one kidney. Partial nephrectomy might preserve long-term kidney function, but it carries higher surgical risks and may leave cancer cells behind. No large trial has directly compared the two approaches in this specific group of patients. The trial will recruit 420 patients across 30 NHS hospitals, randomly assigning them to either partial or radical nephrectomy. Researchers will track kidney function, surgical complications, quality of life, costs, and survival over two years, with longer-term follow-up planned for five to ten years. If partial nephrectomy proves better at preserving kidney function without increasing cancer recurrence or complications, it could become the new standard of care for these patients—potentially reducing rates of chronic kidney disease, cardiovascular events, and the need for dialysis or transplantation.

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RESEARCH QUESTION 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? AIMS/OBJECTIVES Aim: Characterise the trade-off of the potential benefits, harms and costs over a 2-year follow-up in comparing PN & RN 1. Primary objectives: Describe benefits (renal function preservation) & harms (surgical complications) 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 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) METHODS Design: Two-arm multicentre pragmatic superiority RCT (1:1) of PN vs RN Health technology: Minimal invasive surgery for both RN & PN (reflecting normal national practice) Target population (in 30 NHS secondary care sites): 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) 2. Exclusion criteria: Single functioning kidney, multiple renal tumours, reduced eGRF (<60), age <18 Outcome measures: 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) 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) 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 SAMPLE SIZE 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) TIMELINES Study set up 1-6m, recruitment 7-30m (first 9m internal pilot), 2-yr follow up 31-54m, analysis & write up 55-60m IMPACT/DISSEMINATION 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

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