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supported by reliable and precise test able to define an upgrading or upstaging of PCa. The reduction of
costs associated to unnecessary treatment will be devolved for more precise screening and diagnosis able to
improve the quality of life of our patients.

Some of the biomarkers are candidates for identifying more aggressive forms such as HOXD8rc, CXCL14,
SLC16A5rc and GRASP or to predict progression such as DOCKK2, HAPLN3 and FBXO30. It is important
[14]
to note that methylation of some biomarkers that can be found in tissues, cannot be found in ctDNA .
This is because PCa does not release cancer cells if it is at the early stages. Thus, the analysis of cfDNA
methylation associated to the study of PCa tissues, remains a very important task to deepen the role of
cfDNA biomarkers methylation.

In conclusion the studies showed the possibility to analyze the methylation of cfDNA biomarkers either
from plasma or urine, thus opening more possibilities to monitor PCa patients and, possibly to develop
screening programs. A challenge is to study the integration of the anamnestic data, the PSA and the
molecular methylation status on cfDNA to personalize the patient’s care.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception, data search, design and writing of the review: Pavan N,
Scaggiante B
Performed critical revision: Grassi G

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2021.

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