Mortality, Disease Progression and Metastasis in the NIHR HTA Prostate testing for cancer and Treatment (ProtecT) trial: median 20-year follow up

Research question The overarching research question is to determine the comparative effectiveness of the three treatment modalities (surgery, radiotherapy, active monitoring/surveillance) for patients diagnosed with low- or intermediate-risk clinically localised prostate cancer (PCa). Background The NIHR ProtecT (Prostate testing for cancer and Treatment) trial is the only randomised trial comparing these major treatment modalities for localised prostate cancer. ProtecT has shown, up to a median of 15 years, a very low risk of dying from low- and intermediate-risk prostate cancer (c.3%) and no evidence of a difference between the three randomised groups. There was an increased (c.10%) risk of metastases with active monitoring compared with c.5% with surgery or radiotherapy, to be weighed against detailed side-effect profiles showing increased risks of urinary and sexual difficulties from radical treatments. Although some diagnostic and treatments techniques have evolved since ProtecT recruited (1999-2009), no comparable randomised trials exist, and shorter cohort studies of newer techniques have largely replicated ProtecT Patient Reported Outcomes (PROMs). Aims and objectives The aim of this proposal is to follow up ProtecT trial participants to a median of 20 years to evaluate whether: 1. High and similar levels of prostate cancer survival between the three groups will persist 2. The reduction in metastatic disease in the radical treatment groups will translate into a survival advantage for either or both radical options 3. There will be a difference in effectiveness between the two radical treatment groups Methods We propose using the same methods as previously to ensure consistency, accuracy, and continue our high rates of follow-up (98% for clinical data, >99% for vital status) to collect and analyse ProtecT trial participants’ follow up data to a median of 20 years after randomisation. We will obtain relevant routine NHS data from NHS England, verified and supplemented (especially for sites outside England) with data collected by experienced personnel from clinical site electronic patient records (EPR). Primary outcome is PCa-specific mortality (adjudicated by an independent Cause-of-Death committee), with all-cause mortality, metastases, and long-term androgen-deprivation-therapy as secondary outcomes. Timelines for delivery We plan to start in January 2026 after data lock in November 2025 and complete the study by June 2027. Anticipated impact and dissemination The findings will be disseminated widely through journals, social media, blogs, charities and support groups etc. as previously. The findings will provide patients newly diagnosed with low- and intermediate-risk prostate cancer with the information they need to decide their management strategy. The data will allow them to consider the trade-offs between survival and risks of metastases/disease progression extended to a 20-year timescale, set alongside the published side-effects of each treatment modality. The findings will enable additional updates to NICE and international guidelines on the treatment of low- and intermediate-risk prostate cancer and contribute evidence to inform policy about prostate cancer screening and treatment.