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Int J Mol Sci. 2017 May 27;18(6). pii: E1146. doi: 10.3390/ijms18061146.

Epigenetic Signature: A New Player as Predictor of Clinically Significant Prostate Cancer (PCa) in Patients on Active Surveillance (AS).

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Urologic Surgery Unit, European Institute of Oncology, 20141 Milan, Italy.
Institute of Experimental Endocrinology and Oncology (IEOS-CNR) "G. Salvatore", Via Sergio Pansini, 5, 80131 Naples, Italy.
Institute of Genetics and Biophysics "A. Buzzati Traverso", National Research Council (CNR), Via Pietro Castellino 111, 80131 Naples, Italy.
Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, Italy.
Department of Gynecological-Obstetrics Sciences and Urological Sciences, Sapienza Rome University Policlinico Umberto I, 00161 Rome, Italy.
Department of Urology, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy.
Department of Urology, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy.
Department of Translational Medical Sciences, University of Naples Federico II, Via Sergio Pansini, 5, 80131 Naples, Italy.


Widespread prostate-specific antigen (PSA) testing notably increased the number of prostate cancer (PCa) diagnoses. However, about 30% of these patients have low-risk tumors that are not lethal and remain asymptomatic during their lifetime. Overtreatment of such patients may reduce quality of life and increase healthcare costs. Active surveillance (AS) has become an accepted alternative to immediate treatment in selected men with low-risk PCa. Despite much progress in recent years toward identifying the best candidates for AS in recent years, the greatest risk remains the possibility of misclassification of the cancer or missing a high-risk cancer. This is particularly worrisome in men with a life expectancy of greater than 10-15 years. The Prostate Cancer Research International Active Surveillance (PRIAS) study showed that, in addition to age and PSA at diagnosis, both PSA density (PSA-D) and the number of positive cores at diagnosis (two compared with one) are the strongest predictors for reclassification biopsy or switching to deferred treatment. However, there is still no consensus upon guidelines for placing patients on AS. Each institution has its own protocol for AS that is based on PRIAS criteria. Many different variables have been proposed as tools to enrol patients in AS: PSA-D, the percentage of freePSA, and the extent of cancer on biopsy (number of positive cores or percentage of core involvement). More recently, the Prostate Health Index (PHI), the 4 Kallikrein (4K) score, and other patient factors, such as age, race, and family history, have been investigated as tools able to predict clinically significant PCa. Recently, some reports suggested that epigenetic mapping differs significantly between cancer patients and healthy subjects. These findings indicated as future prospect the use of epigenetic markers to identify PCa patients with low-grade disease, who are likely candidates for AS. This review explores literature data about the potential of epigenetic markers as predictors of clinically significant disease.


active surveillance; epigenetic biomarkers; prostate cancer

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