Targeted Biopsy to Detect Gleason Score Upgrading during Active Surveillance for Men with Low versus Intermediate Risk Prostate Cancer.

Abstract

We sought to determine the rate of upgrading to Gleason score 4 + 3 or greater using targeted biopsy for diagnosis and monitoring in men undergoing active surveillance of prostate cancer. Study subjects comprised all 259 men, including 196 with Gleason score 3 + 3 and 63 with Gleason score 3 + 4, who were diagnosed by magnetic resonance imaging/ultrasound fusion guided biopsy from 2009 to 2015 and underwent subsequent fusion biopsy for as long as 4 years of active surveillance. The primary end point was the discovery of Gleason score 4 + 3 or greater prostate cancer. Followup biopsies included targeting of positive sites, which were tracked in an Artemis™ device. Kaplan-Meier curves were generated to determine upgrading rates, stratified by initial Gleason score and prostate specific antigen density. Based on a Cox proportional hazard model, men with Gleason score 3 + 4 were 4.65 times more likely to have upgrading than men with an initial Gleason score of 3 + 3 at 3 years (p <0.01). By the third surveillance year 63% of men with Gleason score 3 + 4 had been upgraded compared with 18.0% who started with Gleason score 3 + 3 (p <0.01). Of all 33 upgrades 32 (97%) occurred at a magnetic resonance imaging visible or a tracked site of tumor, rather than at a previously negative systematic site. Independent predictors of upgrading were Gleason score 3 + 4, prostate specific antigen density 0.15 ng/ml/cm³ or greater and a grade 5 lesion on magnetic resonance imaging. The incidence rate ratio of upgrading (Gleason score 3 + 4 vs 3 + 3) was 4.25 per year of patient followup (p <0.01). During active surveillance of prostate cancer, targeting of tracked tumor foci by magnetic resonance imaging/ultrasound fusion biopsy allows for heightened detection of Gleason score 4 + 3 or greater cancers. Baseline variables directly related to important upgrading that warrant increased vigilance include Gleason score 3 + 4, prostate specific antigen density 0.15 ng/ml/cm³ or greater and grade 5 lesions on magnetic resonance imaging.