Prostate biopsy evolution and the need for repeat biopsy - The role of image and new prostate cancer biomarkers

Prostate Cancer (PC) is the most common malignancy in men, and a diagnosis can only be confirmed following a prostate biopsy (PB). 10-12 cores ultrasound-guided PB is currently the state of the art in the primary diagnosis of PC, presenting clear advantages in terms of detection rate of clinically significant PC, pathology concordance, and both positive and negative predictive value, when compared with the former classical sextant biopsy. Persistent clinical suspicion of PC despite previous negative PB is a challenging topic, with several serum and urinary markers, as well as imaging techniques, aiming to help in the optimal management of these patients.Currently, the most accepted and used methods in clinical practice to reduce the number of unnecessary PBs in this subset of patients are Prostate Cancer Antigen 3 (PCA3) and multiparametric MRI (mpMRI). These methods have shown to improve the diagnostic accuracy of prostatic rebiopsy, but there still aren't clear guidelines defining the optimal strategy in this setting. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PC, highlighting the emerging role of the Prostate Health Index (PHI) and the Four Kallikrein (4k) score. The aim of this review is to demonstrate the evolution to the actual standard 10-12 core ultrasound-guided PB, the indications and controversies concerning repeated PB and to explore the data regarding the potential role of the leading methods affecting the decision to rebiopse - PCA3 and mpMRI -, as well as new PC biomarkers used in the clinical practice (PHI and 4K score).