Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors
Authors: Falagario Ugo G. , Lantz Anna , Jambor Ivan , Busetto Gian Maria , Bettocchi Carlo , Finati Marco , Ricapito Anna , Luzzago Stefano , Ferro Matteo , Musi Gennaro , Totaro Angelo , Racioppi Marco , Carbonara Umberto , Checcucci Enrico , Manfredi Matteo , D’Aietti Damiano , Porcaro Antonio Benito , Nordström Tobias , Björnebo Lars , Oderda Marco , Soria Francesco , Taimen Pekka , Aronen Hannu J. , Perez Ileana Montoya , Ettala Otto , Marchioni Michele , Simone Giuseppe , Ferriero Mariaconsiglia , Brassetti Aldo , Napolitano Luigi , Carmignani Luca , Signorini Claudia , Conti Andrea , Ludovico Giuseppe , Scarcia Marcello , Trombetta Carlo , Claps Francesco , Traunero Fabio , Montanari Emanuele , Boeri Luca , Maggi Martina , Del Giudice Francesco , Bove Pierluigi , Forte Valerio , Ficarra Vincenzo , Rossanese Marta , Mucciardi Giuseppe , Pagliarulo Vincenzo , Tafuri Alessandro , Mirone Vincenzo , Schips Luigi , Antonelli Alessandro , Gontero Paolo , Cormio Luigi , Sciarra Alessandro , Porpiglia Francesco , Bassi PierFrancesco , Ditonno Pasquale , Boström Peter J. , Messina Emanuele , Panebianco Valeria , De Cobelli Ottavio , Carrieri Giuseppe ,   The PROMOD Study Group
Published: October 2023

Abstract
Purpose
The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2).

Methods
This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients.

Results
705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1–2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively.

Conclusions
Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions.

Trial registration
The present study was registered at ClinicalTrials.gov number: NCT05078359.