Negative Biopsies with Rising Prostate-Specific Antigen. What to Do?

Abstract

Introduction: Prostate-specific antigen (PSA) is the main tool of detection for prostate cancer (PCa). However, PSA has limited specificity and sensitivity in determining the presence of PCa, leading to unnecessary biopsies and the diagnosis of potentially indolent PCa. The aim of this article is to review the tools available to urologists in the clinical situation of rising PSA with prior negative biopsies. Evidence synthesis: The need for prostate biopsy is based on PSA level and/or a suspicious digital rectal examination. Ultrasound-guided biopsy is the current gold standard. The incidence of PCa detected by saturation repeat biopsy is 30–43%. Prostate health indes, prostate cancer antigen 3, and 4Kscore are available second-line tests to distinguish between malignant and benign prostate conditions, reducing the number of unnecessary biopsies. Molecular testing including ConfirmMDx (MDxHealth, Irvine, California, USA) and The Prostate Core Mitomic Test™ (PCMT) (MDNA Life Sciences, West Palm Beach, Florida, USA) are tissue tests for men with prior negative biopsy. Multiparametric magnetic resonance imaging (mpMRI) is used for lesion identification and subsequently for biopsy or treatment. In the setting of suspected PCa, the use of prostate mpMRI has shown to have a negative predictive value for clinically significant PCa of 80–96%. Conclusions: Approximately 70% of patients undergoing prostate examination will have a negative result following analysis of the biopsy sample. This negative diagnosis leads to the common clinical challenge of determining when and if a repeat biopsy should be performed. New blood, urine, tissue, and imaging tools are now available to guide this decision.