Figure. Flowchart for inclusion in follow-up (f/u) cohort. HoLEP indicates holmium enucleation of the prostate; mpMRI, multiparametric magnetic resonance imaging; PCa, prostate cancer; PHI, Prostate Health Index; PIRADS, Prostate Imaging Reporting & Data System; PSA, prostate-specific antigen; TURP, transurethral resection of the prostate.

Prostate cancer is the most common solid organ malignancy with an estimated 288,300 new cases in 2023.¹ Advanced screening tools, such as Prostate Health Index (PHI) and multiparametric prostate MRI (mpMRI), have improved detection of clinically significant prostate cancer (csPCa; International Society of Urological Pathology grade group ≥2), while also reducing the number of biopsies performed.^2,3 While many prior studies have evaluated csPCa rates after initial negative mpMRI and systematic biopsy, the subsequent ideal follow-up and risk factors for longitudinal csPCa detection among patients with negative initial mpMRI selected to forgo biopsy are not well characterized.^4,5 Furthermore, the role of omitting biopsy for patients with Prostate Imaging Reporting & Data System (PIRADS) 3 lesions is not well studied, and biopsy practices for patients with PIRADS 3 lesions vary widely. We evaluated the longitudinal csPCa detection rate among biopsy-naïve men with initial PIRADS 1-3 and omission of biopsy with advanced serum biomarkers and mpMRI monitoring.

We retrospectively identified biopsy-naïve men presenting with elevated PSA 2-20 ng/mL from March 2018-June 2021 at our institution, and included men with initial PIRADS 1-3 lesions who were not selected for biopsy with ≥6 months follow-up in our final cohort (see Figure). The primary outcome of interest was subsequent csPCa detection. Clinicopathological data regarding follow-up serum biomarker measurements, repeat mpMRI, and prostate biopsy were obtained. Patients were classified into those who only received follow-up serum biomarker monitoring, those who underwent repeat mpMRI and/or eventual biopsy, and those who underwent transurethral resection of the prostate or holmium enucleation of the prostate. Multivariable logistic regression models evaluated predictors of initial biopsy as well as predictors of mpMRI and biopsy in the follow-up period.

Of 1,494 men who underwent initial mpMRI, 463 (31%) did not pursue biopsy. On multivariable analysis, PSA density ≤0.1, PHI <55, and PIRADS 1 or 2 were significant predictors of omitting initial prostate biopsy. csPCa diagnosis—free survival was 97.6% (326/334) with a median follow-up of 23.1 months (IQR 15.1-34.6). Black race, PSA, PSA density, PHI, as well as PSA and PHI velocity were significant predictors of undergoing repeat mpMRI (15.6%, 52/334) and subsequent biopsy (8.4%, 28/334). Eight men were subsequently diagnosed with csPCa (N=7 on prostate biopsy; N=1 incidentally on holmium enucleation of the prostate). All patients diagnosed with csPCa had PIRADS 4 or 5 on repeat mpMRI. Stratifying by PIRADS score at initial mpMRI, patients with initial PIRADS 1 or 2 vs PIRADS 3 had subsequent csPCa detection rates of 1.8% (5/278) and 5.4% (3/56), respectively.

The limitation of our study is its retrospective nature. There is inherent selection bias as providers selected patients who were deemed safe to omit biopsy. As prostate biopsy was only performed for subsequent suspicion of csPCa, we are unable to ascertain the “true-negative” in our cohort.

Given the prior paucity of data regarding follow-up for reassuring mpMRI with initial omission of prostate biopsy, we report a 2.4% subsequent csPCa diagnosis rate in this population with median follow-up of 23.1 months in our large academic cohort utilizing PHI and mpMRI. This demonstrates a high negative predictive value for initial mpMRI combined with baseline clinical characteristics in selecting patients to forgo biopsy, as well as the safety of serial serum biomarker monitoring with subsequent for-cause mpMRI and prostate biopsy. Importantly, all men with subsequent csPCa detection had upgrade to a PIRADS 4 or 5 lesion on follow-up mpMRI, and our data suggest that it may be safe to continue observing patients who have PIRADS 1-3 on repeat mpMRI.