ERG and PTEN Role on Active Surveillance for Low-Risk Prostate Cancer in the Multiparametric MRI Era.

Background: Our study aimed to correlate ERG and PTEN expressions in prostate biopsy with multiparametric magnetic resonance imaging PI-RADS score, clinical reclassification, and prognosis of very low-risk prostate cancer (PCa) patients under active surveillance (AS).

Methods: We evaluated 101 very low-risk PCa patients under AS between 2013 and 2018. They were followed with DRE, PSA, MRI, and re-biopsies every 1-2 years. Per cause biopsy was recommended if PSA > 10 ng/mL, suspicious DRE, or PI-RADS ≥ 4 was present. ERG and PTEN expressions were assessed by immunohistochemistry at biopsy. Reclassification was defined by PSA > 10 ng/mL, re-biopsy with > 3 positive cores, > 50% positive core, Gleason Score (GS) upgrading ≥ 3 + 4 or extreme GS upgrading ≥ 4 + 3. We correlated ERG and PTEN with reclassification, PI-RADS, pathologic outcomes, and biochemical recurrence in patients surgically treated after reclassification.

Results: After a 49.2-month follow-up, 80% of patients showed reclassification, and GS upgrading was the most common criterion. Seventy-four out of 81 patients with reclassification underwent local treatment and seven had biochemical recurrence during a mean 39.7-month follow-up. At biopsy, positive ERG expression was found in 39.6% of patients and PTEN loss in 12.6%. PTEN loss was associated with GS upgrading (OR = 9.7, p = 0.011) in univariate analysis. PTEN loss was correlated with GS upgrading; these patients had a 9.7-fold greater chance of upgrading when compared to PTEN-positive patients. ERG-positive was associated with PI-RADS ≥ 4 (OR = 2.8, p = 0.026). At multivariate analysis, PI-RADS ≥ 4 was predictor of GS upgrading (OR = 25.2, p < 0.001); MRI PI-RADS score remained an independent factor for extreme GS upgrading, together with PSAd > 0.15 (OR = 15.1, p = 0.012 and OR = 5.76, p = 0.012, respectively).

Conclusions: Neither ERG-positive nor PTEN loss were associated with upgrading during AS. ERG and PTEN biomarkers, despite commonly studied in advanced PCa, have yet no defined role in very low-risk PCa under AS. PI-RADS score was an independent predictor of GS upgrading and extreme upgrading during AS.