Longitudinal Assessment of Urinary PCA3 for Predicting Prostate Cancer Grade Reclassification in Favorable Risk Men during Active Surveillance

BACKGROUND: To assess the utility of urinary prostate cancer antigen 3 (PCA3) as both a one-time and longitudinal measure in men on active surveillance (AS). METHODS: The Johns Hopkins AS program monitors men with favorable-risk prostate cancer with serial PSA, digital rectal examination (DRE), prostate MRI, and prostate biopsy. Since 2007, post-DRE urinary specimens have also been routinely obtained. Men with multiple PCA3 measures obtained over ≥3 years of monitoring were included. Utility of first PCA3 score (fPCA3), subsequent PCA3 (sPCA3), and change in PCA3 were assessed for prediction of Gleason grade reclassification (GR, Gleason score>6) during follow-up. RESULTS: In total, 260 men met study criteria. Median time from enrollment to fPCA3 was 2 years (IQR 1–3) and from fPCA3 to sPCA3 was 5 years (IQR 4–6). During median follow-up of 6 years (IQR 5–8), 28 men (11%) underwent GR. Men with GR had higher median fPCA3 (48.0vs.24.5, p=0.007) and sPCA3 (63.5vs.36.0, p=0.002) than those without GR, while longitudinal change in PCA3 did not differ by GR status (log-normalized rate 0.07vs.0.06, p=0.53). In a multivariable model including age, risk-classification, and PSA density, fPCA3 remained significantly associated with GR (log[fPCA3] odds ratio=1.77, p=0.04). CONCLUSIONS: PCA3 scores obtained during AS were higher in men who underwent GR, but the rate of change in PCA3 over time did not differ by GR status. PCA3 was a significant predictor of GR in a multivariable model including conventional risk factors, suggesting that PCA3 provides incremental prognostic information in the AS setting.