PRostatEctomy Surgery In Disseminated metastatic hormone sensitive prostate cancer with Endpoint assessment using Nuclear imaging Technology using PSMA PET/CT: a randomised controlled full trial (PRESIDENT)

Research Question In men with newly diagnosed low volume metastatic hormone-sensitive prostate cancer (mHSPC) identified on molecular imaging (PSMA PET/CT), does the addition of radical prostatectomy (RP) surgery to standard of care (SOC) therapy improve deterioration-free survival (DFS) compared to SOC therapy alone? Background SOC treatment for low volume mHSPC involves systemic therapies, primarily Androgen Deprivation Therapy (ADT) combined with an Androgen Receptor Pathway Inhibitor (ARPI), often with chemotherapy or radiotherapy. Further, local treatment of the prostate could potentially delay progression and improve both oncological and quality of life (QoL) outcomes in this cohort. This has previously been demonstrated with radiotherapy as the local treatment in the STAMPEDE trial and hence radiotherapy to the prostate is recommended in European and American guidelines for low volume mHSPC. Our preliminary feasibility trial of RP in low volume mHSPC (TRoMbone) showed that local treatment with surgery is safe in this patient group and that a randomised study is feasible. Aims and Objectives We aim to compare deterioration-free survival (DFS) between men receiving RP plus SOC versus those receiving SOC alone. Secondary aims include comparing the incidence of local complications, healthcare resource utilisation and cost-effectiveness, and longer-term oncological outcomes between the two treatment arms. Methods PRESIDENT is a parallel group randomised trial (1:1 ratio) across a minimum of 26 UK centres. Eligible participants are men aged 18 or over with newly diagnosed low volume mHSPC (=4 bone metastases and/or extra-pelvic nodal metastases on a PSMA PET/CT scan), locally resectable (T1-T3) disease, ECOG status 0-1, and suitable for RP within 6 months of starting SOC. The intervention arm will receive RP in addition to SOC therapy. The control arm receives SOC alone which includes ADT+ARPI+/-chemotherapy+/-radiotherapy, plus any newly approved standard therapies. DFS is the primary endpoint defined as the time from randomisation to the earliest occurrence of a clinically significant deterioration in overall health-related QoL measured by EORTC QLQ-C30, metastatic progression on PSMA PET/CT imaging, or death from any cause. Secondary outcomes include progression-free survival and mortality. A cost-effectiveness analysis from an NHS perspective will be conducted over a lifetime horizon. The sample size is 749 men. Timeline 82 months including 10 months set-up, 54 months for recruitment, a minimum of 12 months follow-up, and 6 months for analysis and close-out. The study includes an embedded internal pilot phase with a formal feasibility assessment ("stop/go" criteria) at month 22 (after 12 months of recruitment). Anticipated Impact and Dissemination This study will provide high-level evidence on the clinical and cost-effectiveness of adding RP to SOC therapy for low volume mHSPC across the UK population. BAME communities are highly affected by prostate cancer and the study aims for significant (>30%) representation from these communities. If positive, the results could change global clinical practice by establishing surgery as a treatment that improves long-term cancer and QoL outcomes for men with low volume mHSPC. Findings will be disseminated through peer-reviewed publications, presentations at national and international conferences, clinical guidelines, and patient advocacy groups.