Risk of Upgrading and Upstaging Among 10 000 Patients with Gleason 3 + 4 Favorable Intermediate-risk Prostate Cancer

Abstract

BackgroundIt is unknown whether active surveillance can be safely offered to patients with Gleason 3+4 favorable intermediate-risk (FIR) prostate cancer. ObjectiveTo examine the incidence and predictors of upgrading and upstaging among patients with Gleason 3+4 FIR disease. Design, setting, and participantsThe study involved 10 089 patients in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 3+4 disease, prostate-specific antigen (PSA) <10ng/ml, and cT1c-2a prostate cancer with <50% positive biopsy cores (PBCs) who underwent radical prostatectomy. Outcome measurements and statistical analysisLogistic regression was used to examine predictors of upgrading (pathologic Gleason ≥4+3 or tertiary Gleason 5 in a Gleason 7 tumor) or upstaging (pT3–4/N1). Results and limitationsSome 30.3% of Gleason 3+4 FIR patients were upgraded or upstaged. On multivariable analysis, predictors included higher PSA, percentage PBC, age, and cT2a versus cT1c (all p<0.001), but not black race (p=0.895). When stratified into ordinal variables, PSA 8.1–9.9 versus ≤4.0ng/ml (adjusted odds ratio [AOR] 1.93, 38.3% vs 24.4%), PBC 37.5–49.9% versus <12.5% (AOR 1.79, 37.8% vs 25.1%); highest age quartile (≥67 yr) versus lowest (≤55 yr; AOR 1.46, 35.7% vs 24.7%); and cT2a versus cT1c (AOR 1.33, 34.3% vs 29.8%) were associated with a higher risk of upgrading or upstaging (all p<0.001). Men with PBC <12.5% and PSA ≤4.0ng/ml had a 21.7% risk of more advanced disease. This increased to 44.3% for PBC 37.5–49.9% and PSA 8.1–9.9ng/ml. A limitation of the study is its retrospective nature. ConclusionsApproximately one in three patients with Gleason 3+4 FIR harbored disease of higher grade or stage. Younger patients with low percentage PBC and PSA and cT1c disease have a lower risk and may be candidates for active surveillance. However, widely available clinical information is insufficient for predicting the risk of more advanced disease, and the development and incorporation of additional tools, including magnetic resonance imaging and genomic tests, are necessary. Patient summaryNearly one-third of patients with Gleason 3+4 favorable intermediate-risk prostate cancer harbor disease of higher grade or higher stage than their biopsy and clinical examination suggest. These patients would therefore be poor candidates for active surveillance.