Multi-parametric magnetic resonance imaging (MRI)-guided fusion biopsies are increasingly used in the detection of prostate cancer due to improved sensitivity in detecting clinically significant disease (csPCA).¹ Since the PROMIS trial demonstrated the diagnostic accuracy of MRI in the pre-diagnostic setting, multiple studies have demonstrated improvements in diagnosis using MRI-based biopsy techniques when compared to traditional 12-core biopsy templates.² These include work from Siddiqui et al demonstrating improved sensitivity and data from the PRECISION trial, suggesting a pathway including selective fusion biopsy based on MRI suspicion was superior to 12-core biopsy in detecting csPCA.^1,3 Notably, the MRI-FIRST trial further demonstrated that systematic biopsy when combined with MRI-guided biopsy offers improved sensitivity in the detection of csPCA compared to either modality alone.⁴

While these studies provide near uniform agreement regarding the risk of csPCA in the presence of a “high-risk” lesion (often defined as Prostate Imaging Reporting and Data System [PI-RADS®] 4 or 5) on MRI, not all patients have csPCA in this setting and many have false-positive MRIs. Among men from the PRECISION trial who received only MRI-targeted biopsy, 40% of PI-RADS 4 patients (70) and 17% of PI-RADS 5 patients (54) had either non-csPCA (defined as Gleason Grade Group 1 disease) or no cancer, representing either the absence of csPCA or suboptimal targeting of the biopsy.³ Given the adaptation of prostate MRI and fusion technologies, this clinical scenario is increasingly common. However, few studies have evaluated outcomes among men with a concerning MRI and negative fusion biopsy.

A study by Meng et al described clinical followup of a group of 88 men (18% of the cohort) who had a PI-RADS 4 or 5 MRI with negative fusion and systematic biopsy.⁵ Interestingly, among those who underwent followup MRI 35% had resolution of their PI-RADS 4/5 lesion, 27% had persistent PI-RADS 4/5, and 38% were downgraded to PI-RADS 2/3.⁵ Among the 8 men with a persistent 4/5 lesion who underwent repeat biopsy, 5 (63%) had cancer with 3 (37%) having Gleason Grade Group ≥2, as compared to 2 (23%) with a PI-RADS 2/3 downgrade on repeat MRI having non-csPCA.⁵ These data suggest repeat MRI may help stratify men for risk of undiagnosed prostate cancer, though results are limited by sample size. In addition, a study by Sheridan et al evaluated histological features of PI-RADS 5 lesions with negative fusion biopsy results.⁶ Among 18 lesions with benign pathological results, 39% were benign prostatic hyperplasia nodules, 28% had inflammatory changes, 5% were normal anatomical structures and 28% were discordant with imaging findings.⁶ They also determined that lower prostate specific antigen density (OR=0.88) and lesions located at the apex (OR=3.54) or base (OR=7.11) were associated with benign pathology.⁶ Finally, a followup to the PROMIS study evaluated factors associated with benign pathology in patients with Likert ≥3 MRI lesions and no cancer on systematic or mapping template biopsy.⁷ They observed a number of factors associated with benign results, including lower prostate specific antigen density, low lesion number, small lesion volume and lack of diffusion restriction.⁷ While offering an excellent starting point in evaluating risk among men with a negative biopsy and concerning MRI, further work is needed to determine the best clinical management for this population.

In this session, we plan to discuss this evolving clinical scenario, including further discussion surrounding these and other data related to risk of csPCA among men with a high-risk MRI lesion and negative biopsy. We will consider management options such as variability of MRI images and interpretation, continued prostate specific antigen surveillance, biomarker usage, repeat MRI and the use of additional biopsies. Finally, we will consider the implications of a negative MRI targeted and systematic biopsy, acknowledging the balance between the reassurance offered by a negative test and the risk present in the setting of a “high-risk” MRI.