Identifying men at risk of developing clinically significant prostate cancer (csPCa) who are either biopsy naïve or have undergone a prior negative systematic biopsy remains a dilemma for urologists seeking to utilise clinical resources in a cost‐conscious and safe manner. Clinical and demographic factors including DRE findings, serum PSA concentrations, race/ethnicity, and family history, guide shared decision‐making to pursue an initial or repeat prostate biopsy. Despite thoughtful risk assessments, the screening tools implemented often lead to biopsies where a majority demonstrates benign pathology findings or indolent forms of PCa that would not mandate immediate, definitive intervention. Hence, various risk models (RMs) have been proposed to stratify men who have a greater likelihood of harbouring csPCa, and several now incorporate findings from multiparametric MRI (mpMRI) by assessing suspicious lesion characteristics into their algorithms. While promising, most of these models were generated using single‐institution retrospective data and lack the external validation that could make them more generalisable and widely adopted in clinical practice.
In the present issue, Püllen et al.  evaluate three RMs that incorporate mpMRI findings using a cohort of 307 men who were biopsy naïve or had previously undergone a negative prostate biopsy. Risk of csPCa according to the MRI‐European Randomized Prostate Screening for Prostate Cancer Risk Calculators 3 and 4 (MRI‐ERSPC‐3/4) , Radtke’s RM (ModRAD) , and Distler’s RM (ModDis)  were compared to final pathology after TRUS‐guided perineal prostate biopsy with MRI‐fusion targeted sampling, as indicated using a Prostate Imaging‐Reporting and Data System version 2 (PI‐RADSv2) score ≥3 as the threshold.
The cohort had a median age of 67 years, median PSA concentration of 8.8 ng/mL, and there were 453 PI‐RADSv2 ≥3 lesions, which is consistent with a typical at‐risk screening population. Amongst these men, 134 (40%) harboured csPCa defined as a Gleason Grade Group ≥2. All three RMs performed similarly on receiver operating curve analyses with area under the curve for prediction nearing 0.85 for finding csPCa in both biopsy naïve and prior negative‐biopsy patients. Using a 15% risk threshold, the adapted MRI‐ERSPC‐3/4 RM would have safely avoided 30% of biopsies with 6% of csPCa diagnoses being missed, whereas the ModRad and ModDis RMs would have only avoided 17% and 6% of unnecessary biopsies, respectively, albeit with far fewer occult cases of csPCa.
The integration of mpMRI in the pre‐biopsy setting is being more widely adopted into the clinical landscape, with emerging support largely due to its value in detecting csPCa, but also the recognised high negative predictive value potentiating the safe avoidance or deferral of prostate biopsy . Performing a prostate biopsy in all men with a clinical screening positive PSA and/or DRE carries a significant public health burden, and harbours recognised clinical morbidity without definitive overall survival benefit for many. Hence, integration of MRI findings, importantly the lack of highly suspicious lesions, is of interest in RM assessment to determine which patients would be benefited most from prostate biopsy while sparing some from biopsy, without compromising detection of csPCa and oncological outcomes.
For patients who forgo prostate biopsy based upon factors such as nomogram‐predicted risk of harbouring csPCa, the appropriate timing for performing repeat evaluation with biomarkers and/or MRI is not well defined. Various models have shown much higher rates of biopsy avoidance if accepting some level of missed csPCa . With the awareness that some men who would theoretically avoid a biopsy based on these RMs may actually harbour csPCa, should these men undergo repeat MRI as standard or would serial PSA assessment drive biopsy detection of their csPCa with adequate lead time for definitive treatment? Prospective investigations assessing the clinical course of patients with negative MRI findings who avoid or defer biopsy are critical to determine the real‐world applicability of such RMs. The true value of these RMs and nomograms should balance their public health cost and morbidity benefit with potential oncological risk.
by Zachary A. Glaser and Soroush Rais‐Bahrami
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