Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostatespecific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organbut not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer. KEYWORDS• biomarkers • prostate cancerThe European randomized study of screening for prostate cancer showed that prostate-specific antigen (PSA)-based screening in senior men was associated with a statistically significant 29% prostate cancer mortality reduction [1]. Nevertheless, as many as 40% of those screened are at risk to be treated for a biologically indolent disease that will not affect their life expectancy [1], which results in a 23% negative impact on the life-years gained [2]. The conclusion of one recently published cost-effectiveness analysis was that PSA-based screening should be limited to two or three screens between ages 55 and 59 years because in men older than 63 years overdiagnosis is responsible for loss of quality-adjusted life-years [3]. Several clinical, pathological and biological variables [4] were reported to improve the modest accuracy of PSA as a screening test, although their impact in a community-based setting is yet to be assessed in large trials. An analysis of six externally validated PSA-based models that incorporated readily available variables such as age, race, digital rectal examination, previous biopsies, family history, free PSA, transrectal ultrasonography prostate volume showed that five of these were able to double the sensitivity of PSA testing (44 vs 21%) without loss of specificity [5]. Furthermore, the Prostate Cancer Prevention Trial model can also predict the presence of Gleason ≥7 versus Gleason <7 prostate cancer [6]. Many novel biomarkers also provide valuable prognostic information that can have important therapeutic implications and serve as 400REviEW Ferro, Buonerba, Terracciano et al. future science group selection criteria for patients eligible for active surveillance or candidates for radiotherapy/surgery [7]. In this review, we will focus on the most relevant biomarkers potentially useful for prostate cancer early diagnosis and for assessment of the prognosis of localized disease. Evidence supporting the use of the biomarkers discussed is presented along with a critical analysis of their potential impact on future research and clinical practice. Serum biomarkersPSA is a glycoprotein serine protease that promotes sperm motility via degradation of the semenogelin I and II proteins [8]. In a landmark s...

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