Abstract
Background
The use of prostate-specific antigen density (PSAd) in combination with multiparametric magnetic resonance imaging (mpMRI) of the prostate can improve accuracy of the prostate cancer (PCa) diagnostic pathway. However, it is not clear whether the performance characteristics of PSAd vary according to the index lesion location (ILL) on mpMRI.
Methods
Overall, 2140 patients with positive mpMRI (prostate imaging reporting and data system [PI-RADS] ≥ 3) underwent mpMRI-targeted biopsy (TBx) plus systematic biopsy (SBx) at three tertiary referral centers. Multivariable logistic regression analysis (MVA) tested the interaction between PSAd and ILL (peripheral zone [PZ] vs transitional zone [TZ]) in predicting clinically significant PCa (csPCa, defined as ISUP grade group ≥2) at TBx. Non-parametric locally weighted scatterplots smoothing approach (LOWESS) explored the relationship between PSAd and csPCa according to ILL and stratifying by PI-RADS score.
Results
Median PSA was 6.7 ng/ml. ILL was PZ and TZ in 77% and 23% patients, respectively. Overall, 39% of csPCa cases were diagnosed at TBx. The association between PSAd and csPCa varied according to ILL (interaction test: p < 0.01). In patients with PI-RADS 3 lesions, csPCa incidence was <10% in cases of PSAd values < 0.05 ng/ml/ml and <0.13 ng/ml/ml for PZ and TZ lesions, respectively. Differently, in patients with PI-RADS ≥ 4, csPCa incidence was ≥20% regardless of PSAd value and ILL.
Conclusions
The likelihood of detecting csPCa in patients with PI-RADS 3 lesions is influenced by the combination of PSAd and ILL. Specifically, patients with PZ and TZ PI-RADS 3 lesions have an increased risk of csPCa for PSAd values ≥ 0.05 ng/ml/ml and ≥0.13 ng/ml/ml, respectively. Conversely, patients with PI-RADS ≥ 4 lesions have a non-negligible risk of csPCa regardless of PSAd and ILL.
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AS had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conception and design: LQ, AS Acquisition of data: FP, PS, ML, DC, PZ, AS, AV, FB, SS, RL, AP, EM, LN Analysis and interpretation of data: AS, LQ Drafting of the manuscript: LQ, AS Critical revision of the manuscript for important intellectual content: GB, FDC, RJK, MR, FM, GG, AB Statistical analysis: AS, LQ Supervision: GB, FDC, RJK, MR, FM, GG, AB.
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All methods were performed in accordance with the relevant guidelines and regulations. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of IRCCS San Raffaele Hospital, Milan, Italy. Because this is a retrospective study, there is no approval number for each study. Informed consent was obtained from all subjects involved in the study.
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Quarta, L., Stabile, A., Pellegrino, F. et al. Tailored use of PSA density according to multiparametric MRI index lesion location: results of a large, multi-institutional series. Prostate Cancer Prostatic Dis (2025). https://doi.org/10.1038/s41391-025-00987-4
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DOI: https://doi.org/10.1038/s41391-025-00987-4
