SPCG17: Prostate Cancer Active Surveillance Trigger Trial

STUDY HYPOTHESIS The study hypothesis is that standardized triggers for initiation of curative treatment of men who are in active surveillance will reduce overtreatment without increasing disease progression and prostate cancer mortality. STUDY DESIGN Randomized multi-centre open-label clinical trial INTERVENTIONS Computerized randomisation (1:1) within 12 months from diagnosis of prostate cancer, either to active surveillance according to current clinical practice at the trial centre (reference arm), or to a standardised active surveillance protocol applying specific criteria for repeat biopsies and the initiation of curative treatment (experimental arm). Patients are stratified by centre and Gleason score. Follow-up both groups: PSA every 6 months, clinical examination (with PSA test) annually, and MRI every second year. Repeat biopsies (reference arm): Current practice Repeat biopsies (experimental arm), standardised triggers: 1. A systematic repeat biopsy if PSA density increases to \> 0.2 ng/ml/cc, and then at every 0.1 ng/ml/cc increase 2. MRI progression in men with previously only Gleason grade 3+3: 5 mm or more increase in size in any dimension of a measurable lesion, increase in PI-RADS score to 3-5, a new lesion with PI-RADS score 3-5, or high or very high suspicion of extra-capsular extension or seminal vesicle invasion 3. MRI progression in men with Gleason grade 3+4: 5 mm or more increase in size in any dimension of a measurable lesion, or a new lesion with PI-RADS score 3-5 Curative treatment (reference arm): Current practice Curative treatment (experimental arm), standardised triggers: 1. MRI progression in lesions with confirmed Gleason grade 4: increase in PI-RADS score to 4 or 5, or high or very high suspicion of extra-capsular extension or seminal vesicle invasion 2. Pathological progression: Gleason pattern 5, primary Gleason pattern 4 in any core with 5 mm or more cancer, Gleason 3+4 in 3 or more cores or 30% if more than 10 cores are taken, or Gleason 3+4 in 10 mm or more cancer Patients will be followed continuously until initiation of treatment, the event of metastasis, to a break point where active surveillance is considered terminated and watchful waiting starts, or to death of any cause. For men who discontinue active surveillance, the follow-up and management continue according to standard clinical practice but with annual reporting in the study.