Prostate Cancer Antigen 3 Score Does Not Predict for Adverse Pathologic Features at Radical Prostatectomy or for Progression-Free Survival in Intermediate- and High-Risk Prostate Cancer

Abstract

Pre-operative urinary prostate cancer antigen 3 (PCA3) gene scores predict for adverse pathologic features (APF) at radical prostatectomy (RP) in men with low- and intermediate-risk prostate cancer (PCa). However, whether these predict for APF in men with higher-risk disease, or for progression-free survival (PFS) in general, is unknown. We retrospectively investigated whether PCA3 scores were predictive for APF or PFS in men with higher-risk PCa. One hundred nine men with cT1-T2 National Comprehensive Care Network (NCCN) intermediate- and high-risk PCa were treated with RP from 2010-2015. Logistic regression analysis was performed to evaluate the association of PCA3 score with selected APFs—seminal vesicle invasion [SVI], lymph node positivity (pLN+), upgrading to Gleason score (pGS) 8-10 or tertiary pattern 5, and upstaging to pT3 disease—after adjusting for age, initial PSA (iPSA), clinical T-stage, biopsy GS, percent positive biopsies (PPB), and MRI T-stage. Biochemical recurrence was defined as confirmatory PSA ≥ 0.2 ng/mL or initiation of salvage therapy. Among 78 men with ≥ 1 year follow-up, the association between PCA3 score and PFS was assessed using Cox regression analysis after adjusting for age, pre-operative risk group, maximal tumor diameter (MTD), pGS, extracapsular extension (ECE), SVI, and pLN+. Kaplan-Meier analysis was performed to estimate 3-year PFS. Median follow-up was 2.3 years. Forty-eight percent had intermediate-risk and 52% had high-risk PCa. At RP, 42% had ECE, 10% had SVI, and 10% had pLN+. Twenty-one percent experienced GS upgrading and 41% were upstaged to pT3. On multivariate analysis (MVA), multiple significant predictors for individual APFs were elucidated, including increasing bGS predicting for SVI (OR 6.80, p=0.040), increasing iPSA and PPB predicting for pLN+ (ORs 1.12 and 1.06; p<0.05 for both), and increasing bGS, iPSA, and PPB predicting for upstaging to pT3 (ORs of 3.64, 1.08, and 1.03; p<0.05 for all). Overall, 3-year PFS was 70%. No significant predictors for PFS were found on MVA, but NCCN risk group (hazard ratio [HR] 4.17), MTD (HR 1.83), ECE (HR 2.69), SVI (HR 3.04), pLN+ (HR 3.70), and pGS (HR 4.79) were all significant on univariate analysis (UVA, p<0.05 for all). PCA3 score was not associated with any APF or with PFS on UVA or MVA. Unlike in lower-risk cohorts, PCA3 score was not associated with any APF in this higher-risk cohort, despite enrichment for APFs. Similarly, despite a relatively high number of biochemical recurrences, PCA3 score was not associated with PFS. Notably, multiple known pre-operative predictors for APFs were significant on MVA, and multiple predictors were associated with PFS on UVA. These results suggest that PCA3 may not be a useful adjunct predictive marker in men with higher-risk PCa.