Objective: In recent years, several biomarkers alternative to standard prostate
specific antigen (PSA) for prostate cancer (PCa) diagnosis have become available. The aim of
this systematic review is to assess the current knowledge about alternative serum and urinary
biomarkers for the diagnosis of PCa.
Material and Methods: A research was conducted in Medline, restricted to English language
articles published between December 2014 and June 2018 with the aim to update previously
published series on PCa biomarkers. The preferred reporting items for systematic reviews and
meta-analyses (PRISMA) criteria were used for selecting studies with the lowest risk of bias.
Results: Emerging role and actual controversies on serum and urine alternative biomarkers to
standard PSA for PCa diagnosis, staging and prognosis assessment, such as prostate health
index (PHI), PCA3, ConfirmMDx, Aberrant PSA glycosylation, MiPS, miRNAs are critically
presented in the current review.
Conclusion: Although the use of several biomarkers has been recommended or questioned by
different international guidelines, larger prospective randomized studies are still necessary to
validate their efficacy in PCa detection, discrimination, prognosis and treatment effectiveness.
To date, only PHI and 4Kscore have shown clinical relevance for discriminating more aggressive
PCa. Furthermore, a new grading classification based on molecular features relevant for
PCa risk-stratification and tailoring treatment is still needed.