RESUMEN
INTRODUCTION: In cases of persistent suspicion of prostate cancer (PC), repeat prostate biopsies (PB) are frequently performed in spite of their low yield. In the context of a negative PB, there is a microscopic scenario (MS), which we define as the group of recognizable non-neoplastic lesions. While some of these lesions seem to have a protective effect, the existence of others increases the risk of PC detection in posterior PB. The objective of this systematic review is to identify the lesions that may belong to the MS of a negative PB and analyse the current evidence of their association with the risk of detecting PC in subsequent PBs. EVIDENCE ACQUISITION: Two independent reviewers conducted a literature search on Medline, Embase and Central Cochrane with the following search terms: small acinar proliferation, ASAP, prostatic intraepithelial neoplasia, HGPIN, adjacent small atypical glands, pinatyp, atrophy, proliferative inflammatory atrophy, pia, prostatic inflammation, prostatitis and prostate cancer. 1,015 references were first identified, and 57 original articles were included in the study, following the PRISMA declaration and the PICO selection principles. EVIDENCE SYNTHESIS: Atypical small acinar proliferation is associated with PC detection in repeat PB with rates ranging between 32 and 48%. High-grade prostatic intraepithelial neoplasia (HGPIN) is related to PC in 13 to 42% of cases. Studies show that HGPIN, when multifocal, is a significant independent risk factor for PC. Prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation seem to act as protective factors on the detection of PC in repeat PB. On the other hand, the risk of PC detection reduces significantly in male patients with multifocal HGPIN and coexistent PIA. CONCLUSIONS: The MS of a negative PB may include atypical small acinar proliferation, HGPIN, prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation lesions, since they all seem to be associated with the risk of PC detection in repeat PB. This review has led us to create the hypothesis that the MS of a negative PB might be a valuable and useful tool when considering repeat PB.