CUA 2017: Defining a Cohort of Men Who May Not Require Repeat Prostate Biopsy Based on Negative Predictive Value of PCA3 and MRI Combined: The Double-Negative Effect

Toronto, Ontario ( At the prostate cancer podium session at the 2017 CUA meeting, Dr. Nathan Perlis from the University of Toronto presented early results of men with a negative prostate biopsy who then subsequently had a negative PCA3 biomarker test and negative multiparametric MRI (mpMRI) to assess if they require a repeat biopsy.

Both the PCA3 urine biomarker and mpMRI aim to limit prostate cancer over-diagnosis and over-treatment by identifying less indolent cancer and more clinically significant cases. The objective of this study was to explore whether the utility of these tests can be maximized by combining them for a group of patients with previous negative biopsies.

For this study, clinicopathologic data was collected on 470 men with a previous negative biopsy or on active surveillance (AS) for low-risk prostate that underwent a PCA3 test from 2011 to 2016. Covariates included age, PSA, mpMRI, digital rectal exam (DRE), family history, and prostate size. Patients were then stratified by mpMRI and PCA3 results to detect whether any combination of tests had improved negative predictive value (NPV) and considered the optimal sequence of testing. Multivariable modeling was performed to predict clinically significant prostate cancer on repeat biopsy as defined by the Epstein criteria (insignificant disease = Gleason score of 6 or less, less than one-third of positive cores and an involvement of 50% or less of individual cores). 

Patients included had a median age of 63 years (IQR 58-68), median PSA of 6.3 ng/mL (IQR 4.6-8.8), and abnormal PCA3 (≥35) in 32.5% of cases. In the multivariable model for predicting clinically significant prostate cancer, only age (OR 1.07, 95%CI 1.02-1.13), PIRADS score 4 (OR 10.3, 95%CI 2.8-38.3), PIRADS score 5 (OR 24.9, 95%CI 6.2-101.2), and abnormal PCA3 (OR 2.57, 95%CI 1.19-5.6) were significant. No patients with a negative mpMRI and normal PCA3 had clinically significant prostate cancer on subsequent biopsy (0 of 26, 100% NPV for double-negative test; p<0.001). Using mpMRI as the initial test diminished the number of overall tests (11 fewer tests per 100 patients) used, however is the most expensive approach that requires an expert radiologist and dedicated time/equipment. A limitation of the study includes the low number of men receiving a mpMRI with PIRADS 4 or 5 lesions, as suggested by the wide confidence intervals on multivariable modelling. 

The authors concluded that both PCA3 and mpMRI are useful tests for predicting clinically significant prostate cancer on repeat prostate biopsy, as no patients in their cohort had clinically significant disease when both tests were negative. Perhaps a subsequent biopsy can be eliminated in this setting, although these results require external validation on larger and more heterogeneous groups of men.

Presented By: Nathan Perlis, MD, University of Toronto, University Health Network, Toronto, ON, Canada

Co-Authors: Thamir Al-Kasab, Ardalan E. Ahmad, Estee Goldberg, Kamel Fadaak, Rashid Sayyid, Antonio Finelli, Girish S. Kulkarni, Robert J. Hamilton, Alexandre Zlotta, Neil E. Fleshner

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre  Twitter: @zklaassen_md at the  72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada