The Epstein criteria predict for organ-confined prostate cancer but not for minimal residual disease and outcome after radical prostatectomy

Objective: The Epstein criteria (EC) used to select men for active surveillance do not predict biologically insignificant diseases. Minimal residual disease (MRD) is an undetected microscopic disease that remains after radical prostectomy (RP) and is a biological classification associated with the risk of treatment failure. Subtypes of MRD, the 10-year biochemical failure free survival (BFFS), and restricted mean biochemical failure free survival time (RMST) were determined and compared in EC patients treated with RP. Material and methods: Consecutive patients with a Gleason 6 biopsy treated at a single institution were divided into those who did or did not fulfill the EC and underwent RP. One month after surgery, samples were taken for the detection of circulating prostate cells (CPCs) and bone marrow micrometastasis. MRD was defined as negative for both CPCs and micrometastasis; patients were positive for micrometastasis and CPCs separately. BFFS for up to 10 years and RMST were determined for each MRD subgroup for EC positive and negative patients. Results: EC positive men (137/426) were significantly older (p<0.05) and had negative MRD, pT2 ( pathologically organ confined) disease (<0.02), and lower frequency of upgrading (p<0.02). Of the EC positive men, 71% were MRD negative, 13% were positive for micrometastasis, and 16% were positive for CPCs with respective 10-year BFFS of 99%, 89%, and 21% (<0.001) (hazard ratio: 1.00, 1.76, 4.03, respectively) with no signficant differences between the 10-year BFFS or RMST for MRD subgroups for EC positive and negative patients. Conclusions: EC predict pT2, MRD negative disease; however, 29% are MRD positive with a high risk of treatment failure.