Adverse Disease Features in Gleason Score 3 + 4 “Favorable Intermediate-Risk” Prostate Cancer: Implications for Active Surveillance

Abstract

BackgroundAccording to a recent National Comprehensive Cancer Network (NCCN) guidelines update, patients with Gleason score (GS) 3 + 4 prostate cancer (PCa) and “favorable intermediate-risk” (FIR) characteristics might be offered active surveillance (AS). However, the risk of unfavorable disease features and its prediction in this subset of patients is not completely understood. ObjectiveTo identify the risk of unfavorable disease and potential predictors of adverse outcomes among GS 3 + 4 FIR PCa patients. Design, setting, and participantsThe study included patients with biopsy GS 3 + 4 and otherwise fulfilling the NCCN low-risk definition (prostate-specific antigen [PSA] <10 ng/ml, cT2a or lower) undergoing radical prostatectomy (RP) from 2006 to 2014 at a single institution. Outcome measurements and statistical analysisComplete information on PSA, PSA density (PSAD), clinical stage, percentage of positive cores, percentage of maximum surface specimen involvement, and RP pathology were available. GS upgrade and downgrade, non–organ-confined and non–specimen-confined disease, unfavorable disease (pT3–T4 and/or pN1 and/or a pGS ≥4 + 3) were the outcomes. Statistical analysis included descriptive statistics and multivariable logistic regression. Results and limitationsA total of 156 patients (13.1%) experienced GS upgrade; 201 (16.9%) were downgraded. Overall, 205 men (17.2%) harbored non–organ-confined disease, and 295 (24.8%) had unfavorable disease. Age (odds ratio [OR]: 1.06), percentage surface involvement (OR: 1.01), and PSAD (OR: 1.83) were the only significant predictors of upgrade. Age (OR: 1.05), clinical stage (OR: 1.74), percentage of positive cores >50% (OR 1.57), percentage of surface area (OR: 1.02), and perineural invasion (OR: 1.89) were significant predictors of unfavorable disease at RP. The retrospective design is a limitation. ConclusionsAS is a possible option for a subset of men with FIR GS 3 + 4. However, clinical models alone have a limited role in GS upgrade prediction, and alternative tools warrant further investigation. Patient summaryPatients with Gleason score 3 + 4 at biopsy, low prostate-specific antigen, and low stage might consider the option of active surveillance, but the use of clinical information alone might be not adequate for thorough risk-adapted counseling.