10 PROTEUS: Standard of care at the present time is surgery alone. The trial compared androgen deprivation (ADT) with GNRH analogue injections as a control arm. ADT is not standard of care, but the trialists believed patients would not agree to a trial where they may not receive any therapy at all except for the prostatectomy, therefore the control arm had to offer treatment other than just observation. The trial design: patients were randomised into 2 groups, one group receiving ADT and apalutamide (oral androgen receptor pathway inhibitor) for 6 months prior to surgery/neo adjuvant therapy versus ADT alone, followed by surgery and then completing another 6 months with the same protocol in the adjuvant setting. The number of patients enrolled in the trial was 2 109. They were stratied by Gleason score, nodal status, and geographic region before being randomly assigned to either group. It accrued from 18 countries making the population of the study diverse. The trial was designed to answer 2 questions: The dual primary end points were: 1: Pathological complete response/minimal residual disease (PCR/MRD) - dened as a pathological stage of ypT2 or lower, with a tumor size of ≤5 mm in the greatest dimension at the time of surgery. 2: Metastasis-free survival (MFS), as assessed with conventional imaging or prostate-specic membrane antigen positron-emission tomography. (PSMA-PET) By pairing pCR/MRD with MFS as dual primary endpoints, the trial was designed to assess both early tumour response at surgery and whether that response translated into meaningful long-term benet. Secondary end points included event-free survival (EFS), rst subsequent treatment, and distant metastasis (assessed in time-to-event analyses), as well as safety. First endpoint: 8.9% of patients had no detectable cancer and another 30.6% had a tumour smaller than ypT2 (pathology stage less than ypT2 such as ypT0 or ypT1). This is almost 40% in total, indicating that after androgen deprivation therapy, the tumour has either completely disappeared or is microscopic, with no cancer found in the surgical specimen. Second endpoint: The 5-year Median metastasis-free survival rate was 78.2% in the combination arm and 73.5% in the control arm (ADT alone), compared to an average of 50% with surgery alone.
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