Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer?

Samuel A. Gold, Graham R. Hale, Jonathan B. Bloom, Clayton P. Smith, Kareem N. Rayn, Vladimir Valera, Bradford J. Wood, Peter L. Choyke, Baris Turkbey, Peter A. Pinto

Multiparametric magnetic resonance imaging (mpMRI) has improved clinicians' ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx. A literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed "PCa mimics," that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement. Despite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from "PCa mimics" or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy. A better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options.