Added Value of Prostate-specific Antigen Density in Selecting Prostate Biopsy Candidates Among Men with Elevated Prostate-specific Antigen and PI-RADS ≥3 Lesions on Multiparametric Magnetic Resonance Imaging of the Prostate: A Systematic Assessment by PI-RADS Score

Francesco Pellegrino; Armando Stabile; Gabriele Sorce; Leonardo Quarta; Daniele Robesti; Donato Cannoletta; Giuseppe Cirulli; Francesco Barletta; Simone Scuderi; Elio Mazzone; Mario de Angelis; Giorgio Brembilla; Francesco De Cobelli; Andrea Salonia; Francesco Montorsi; Alberto Briganti; Giorgio Gandaglia

doi:10.1016/j.euf.2023.10.006

Added Value of Prostate-specific Antigen Density in Selecting Prostate Biopsy Candidates Among Men with Elevated Prostate-specific Antigen and PI-RADS ≥3 Lesions on Multiparametric Magnetic Resonance Imaging of the Prostate: A Systematic Assessment by PI-RADS Score

Eur Urol Focus. 2023 Oct 19:S2405-4569(23)00223-7. doi: 10.1016/j.euf.2023.10.006. Online ahead of print.

Authors

Francesco Pellegrino¹, Armando Stabile², Gabriele Sorce², Leonardo Quarta², Daniele Robesti², Donato Cannoletta², Giuseppe Cirulli², Francesco Barletta², Simone Scuderi², Elio Mazzone², Mario de Angelis², Giorgio Brembilla³, Francesco De Cobelli³, Andrea Salonia², Francesco Montorsi², Alberto Briganti², Giorgio Gandaglia²

Affiliations

¹ Division of Oncology/Unit of Urology, Soldera Prostate Cancer Laboratory, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: pellegrino.francesco@hsr.it.
² Division of Oncology/Unit of Urology, Soldera Prostate Cancer Laboratory, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
³ Department of Radiology, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

PMID: 37865591
DOI: 10.1016/j.euf.2023.10.006

Abstract

Background: A significant proportion of patients with positive multiparametric magnetic resonance imaging (mpMRI; Prostate Imaging-Reporting and Data System [PI-RADS] scores of 3-5) have negative biopsy results.

Objective: To systematically assess all prostate-specific antigen density (PSAD) values and identify an appropriate cutoff for identification of patients with positive mpMRI who could potentially avoid biopsy on the basis of their PI-RADS score.

Design, setting, and participants: The study included a cohort of 1341 patients with positive mpMRI who underwent combined targeted and systematic biopsies.

Outcome measurements and statistical analysis: Multivariable logistic regression analysis (MVA) was used to assess the association between PSAD and the risk of clinically significant prostate cancer (csPCa, grade group ≥2) after adjusting for confounders. We used locally weighted scatterplot smoothing to explore csPCa risk according to PSAD and PI-RADS scores. PSAD utility was observed only for patients with PI-RADS 3 lesions, so we plotted the effect of each PSAD value as a cutoff for this subgroup in terms of biopsies saved, csPCa cases missed, and clinically insignificant PCa (ciPCa, grade group 1) cases not detected.

Results and limitations: Overall, 667 (50%) csPCa cases were identified. On MVA, PSAD independently predicted csPCa (odds ratio 1.57; p < 0.001). For PI-RADS ≥4 lesions, the csPCa risk was ≥40% regardless of PSAD. Conversely, among patients with PI-RADS 3 lesions, csPCa risk ranged from 0% to 60% according to PSAD values, and a PSAD cutoff of 0.10 ng/ml/cm³ corresponded to a threshold probability of 10% for csPCa. Using this PSAD cutoff for patients with PI-RADS 3 lesions would have saved 32% of biopsies, missed 7% of csPCa cases, and avoided detection of 34% of ciPCa cases. Limitations include selection bias and the high experience of the radiologists and urologists involved.

Conclusions: Patients with PI-RADS ≥4 lesions should undergo prostate biopsy regardless of their PSAD, while PSAD should be used to stratify patients with PI-RADS 3 lesions. Using a threshold probability of 10% for csPCa, our data suggest that the appropriate strategy is to avoid biopsy in patients with PI-RADS 3 lesions and PSAD <0.10 ng/ml/cm³. Our results also provide information to help in tailoring an appropriate strategy for every patient with positive mpMRI findings.

Patient summary: We investigated whether a cutoff value for PSAD (prostate-specific antigen density) could identify patients with suspicious prostate lesions on MRI (magnetic resonance imaging) who could avoid biopsy according to the PI-RADS score for their scan. We found that patients with PI-RADS ≥4 should undergo prostate biopsy regardless of their PSAD. A PSAD cutoff of 0.10 should be used to stratify patients with PI-RADS 3.

Keywords: Magnetic resonance imaging; Prostate Biopsy; Prostate Imaging-Reporting and Data System; Prostate-specific antigen density; Prostatic Cancer.