Radical prostatectomy (RP) represents one treatment option for clinically localized prostate cancer (PCa). The most updated guidelines of the European Association of Urology indicate the need to perform ePLND in patients with a lymph node invasion (LNI) risk >5% according to the Briganti nomogram. This approach allows sparing ePLND in two thirds of contemporary surgically treated patients; however, many patients still receive ePLND in the absence of lymph node metastases. This is clinically relevant, since ePLND is associated with significant risks of complications.

Improving the ability to detect LNI in PCa would be important for two main reasons: (1) enabling more timely treatments that may improve patient outcomes, and (2) avoiding significant overtreatment and reducing ePLND-related toxicity.

The hypothesis of the present study is that lymphatic spread of PCa cells may be predicted through integration of clinical variables, radiologic findings, and epigenomic information. The objective of the study is to develop an accurate predictive model including radiological and epigenomic information.

Inclusion Criteria:

• Patients diagnosed with localized prostate cancer (cTanyN0M0) who underwent radical prostatectomy and extended PLND
• All included patients presented one or multiple lesions at the mp-MRI of the prostate, defined as PI-RADS 3 to 5
• At least two biopsy cores were required: i) one positive core from the mp-MRI PI-RADS 3- 5 lesion/s (target lesion), ii) one positive core from the systematic sampling (outside the target lesion)

Exclusion Criteria:

• Unavailable or negative mp-MRI, unavailable or negative target or systematic biopsy, and refute to undergo radical prostatectomy with PLND at the Ospedale San Raffaele

Data collection followed the principles outlined in the Declaration of Helsinki. All enrolled patients signed an informed consent form agreeing to supply their own anonymous information and tissue specimens for this and future studies.