A Tailored Polygenic Risk Score for Predicting Progression in Prostate Cancer Under Active Surveillance

NCT07491406 | Completed

• 1 other identifier: PRS-AS
• Study Type: observational
• Target: 185
• Locations: 1 country
• Sites: 1

Brief Summary

Prostate cancer is the most common malignancy in men, and in patients with low-risk disease, active surveillance represents the preferred initial approach to avoid unnecessary treatments. However, up to 50% of men under active surveillance develop clinical progression or histological upgrading within five years, making improved risk stratification essential. A family history of prostate cancer is a well-established risk factor and reflects the importance of genetic predisposition. Genome-wide studies have identified numerous common variants associated with disease risk, enabling the development of polygenic risk scores (PRS) that integrate the effects of multiple genetic loci. Recent evidence suggests that these PRS may also correlate with tumor aggressiveness and the likelihood of progression in patients undergoing active surveillance. This study aims to analyze 185 patients, stratified according to the presence or absence of family history and progression during active surveillance, using germline DNA that has already been biobanked and analyzed with the Axiom™ PMDA array. PRS will be calculated as a weighted sum of risk variants. The objective is to identify PRS models capable of accurately predicting progression, with particular focus on men with a family history, thereby improving the personalization of clinical monitoring. By integrating genomic and clinical data, the study seeks to support a precision oncology approach in patients with early-stage prostate cancer.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Polygenic risk score

Outcome Measures

Primary Outcomes (1)

• Disease progression

  Disease progression during active surveillance, defined as the occurrence of histological upgrading at repeat biopsy

  at confirmatory biopsy

Study Arms (2)

PCa Family History

Non PCa Family History

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with prostate cancer undergoing an active surveillance protocol.

You may qualify if:

• Diagnosis of low-risk PCa (Gleason score ≤7 )
• PSA \<20 ng/mL
• Clinical stage ≤T3
• Enrollment in AS with confirmatory biopsy and longitudinal follow-up
• Reported family history
• Signed URBAN consent
• Signed protocol N. 2014 - BIOPSIE PROSTATICHE e PROSTATECTOMIE RADICALI

You may not qualify if:

• Absence of a biological sample available in the biobank.
• Lack of complete clinical data related to diagnosis or follow-up during active surveillance.
• Failure to perform the confirmatory biopsy required by the active surveillance protocol.
• Lack of information on family history.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS San Raffaele

Milan, IT, 20132, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

Prostatic Neoplasms; Genetic Risk Score

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Genetic Predisposition to Disease; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: March 24, 2026
• Study Start: January 1, 2018
• Primary Completion: December 31, 2025
• Study Completion: March 18, 2026
• Last Updated: May 15, 2026

Record last verified: 2026-05

Locations

IT (1)