Incidence and Predictors of Upgrading and Upstaging Among 10,000 Patients with Gleason 3+4 Favorable Intermediate-Risk Prostate Cancer: Implications for Active Surveillance

Abstract

Whether active surveillance can be safely offered to patients with intermediate-risk prostate cancer, particularly those with Gleason 3+4 favorable intermediate-risk (FIR) disease, is unknown. We studied this question by examining the incidence and predictors of upgrading and upstaging among patients with Gleason 3+4 FIR disease. We identified 10,089 patients in the National Cancer Database diagnosed from 2010 through 2012 with Gleason 3+4, PSA<10 ng/mL, and cT1c-2a prostate cancer with <50% positive biopsy cores (PBC) without clinical evidence of nodal or metastatic disease who were treated with radical prostatectomy. Multiple logistic regression was used to examine factors associated with upgrading (pathological Gleason 4+3 or 8-10) or upstaging (pT3-4 or pN1). 27.7% of all Gleason 3+4 FIR patients (2,793) were upgraded or upstaged (15.6% upgraded and 17.0% upstaged). On multivariable analysis, predictors of upgrading or upstaging include higher PSA, percentage of PBC, and cT stage, as well as older age (p<0.001 for all), but not Black race (p=0.651). When stratified into ordinal variables, PSA 8.1-9.9 ng/mL vs. 2.1-4.0 ng/mL (AOR 1.98, 34.9% vs. 21.4%); 37.5-49.9% vs. <12.5% PBC (AOR 1.77, 34.2% vs. 22.4%); cT2a vs. cT1c stage (AOR 1.32, 31.8% vs 27.1%); and highest quartile age (≥67) vs. lowest (≤55; AOR 1.45, 32.7% vs. 22.3%) were associated with increased risk of upstaging or upgrading (p<0.001 for all). 40.3% of men age ≥67 with 37.5-49.9% PBC were upgraded or upstaged. Overall, just over 1 in 4 Gleason 3+4 FIR patients were upgraded or upstaged after radical prostatectomy. Younger patients with low PBC, low PSA, and cT1c stage have a lower risk of harboring higher grade or stage disease and may be candidates for active surveillance. However, models based on widely available clinical information are insufficient for predicting the risk of more advanced disease, and research is necessary into developing and incorporating additional tools, including magnetic resonance imaging and genomic tests.