SPCG-17 - when to treat men who are in active surveillance for prostate cancer, a randomized study comparing current practice with standardized triggers for initiation of curative treatment

INTERVENTION: Computerized randomisation (1:1) within 12 months from diagnosis of prostate cancer, either to active surveillance according to current practice at the trial centre (reference arm), or to a standardised active surveillance protocol applying specific criteria for initiating curative treatment (experimental arm). Patients are stratified by centre and Gleason score. Follow‐up in the reference arm (current practice at the trial centre): PSA every 6 months, clinical examination (with PSA test) annually, and multiparametric MRI (with targeted biopsies at suspicious lesions) every second year. Repeat biopsies and/or other examinations can be initiated according to the urologist’s judgement. Follow‐up in the experimental arm (criteria for intervention): PSA every 6 months, clinical examination (with PSA test) annually, and multiparametric MRI (with targeted biopsies at suspicious lesions) every second year. Repeat biopsies and/or curative treatment is initiated if specific criteria are fulfilled (see below). Criteria for repeat biopsies (experimental arm only): 1. A systematic repeat biopsy if PSA density increases to > 0.2 ng/ml/cc 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, new suspicion of extra‐capsular extension or seminal vesicle invasion, or a new lesion with PI‐RADS score 3‐5) 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) Criteria for curative treatment (experimental arm only): 1. MRI progression in lesions with confirmed Gleason grade 4 (increase in PI‐RADS score to 4 or 5, or new 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 CONDITION: Active surveillance for low‐risk and favourable intermediate‐risk prostate cancer ; Cancer ; Low‐ and favourable intermediate‐risk prostate cancer PRIMARY OUTCOME: The primary outcome is progression‐free survival, which is defined as cumulative incidence of PSA relapse after curative treatment and cumulative incidence of androgen deprivation therapy in untreated men. ; ; The first analysis for the primary endpoint will be performed 1 year after inclusion of the last patient. Subsequent analyses for primary (and secondary) endpoint will be performed every 3 years. Final outcome at 10 years is cumulative prostate cancer mortality.; SECONDARY OUTCOME: 1.Cumulative incidence of pT3 at radical prostatectomy specimens; 2. Cumulative incidence of metastasis (will be assessed after each follow‐up examination); 3. Cumulative number of treatments with curative intent (mainly radical prostatectomies or local radiotherapy); 4. Cumulative incidence of switch to watchful waiting; 5. Quality of life (will be assessed from questionnaires at baseline and every 2 years); 6. Costs; ; The first analysis for secondary endpoints will be performed 1 year after inclusion of the last patient. ; INCLUSION CRITERIA: The inclusion criteria are: 1. Recently (within 12 months) diagnosed adenocarcinoma of the prostate 2. Tumour stage = T2a, NX, M0 (former MX) 3. PSA <15 ng/ml, PSA density = 0,2 ng/ml/cc 4. Gleason pattern 3+3=6 (any number of cores, any cancer involvement) or Gleason pattern 3+4=7 (<3 cores (or <30 % of cores if more than ten cores are taken), <10 mm cancer in one core) 5. Life expectancy >10 years with no upper age limit 6. Candidate for curative treatment if progression occurs 7. Signed written informed consent