ProFam-Risk registry aims to establish model for personalized prostate cancer prevention

Investigators from University Hospital Düsseldorf in Germany are seeking to validate a personalized counseling and monitoring strategy for patients who are at an increased risk of prostate cancer due to positive family history or pathogenic genetic variants.¹

The prospective registry, called ProFam-Risk (NCT05681416), is enrolling participants across 3 cohorts: men without known prostate cancer who have an increased familial risk of prostate cancer (defined as at least 2 first-degree relatives with prostate cancer at any age or 1 first-degree relative with early onset prostate cancer); men without known prostate cancer who have confirmed pathogenic germline variants associated with prostate cancer; and men 40 years and older who have diagnosed prostate cancer and a familial and/or genetic risk.

Across these cohorts, the study aims to identify likely pathogenic or pathogenic variants or novel cancer signaling pathways, evaluate multiparametric MRI (mpMRI) for prostate cancer prevention in high-risk individuals, and assess psychosocial factors as part of thepsychosocial subproject ProFam-Psych.

According to the authors, “ProFam-Risk may serve as a proof-of-concept project by demonstrating the feasibility, clinical utility, and added value of an integrated, interdisciplinary high-risk screening approach, including patient acceptance, psychological outcomes, and adherence to follow-up recommendations.”

Participants in the study will first be seen by the urology department at the University Hospital Düsseldorf, where they will receive counseling on the consequences of genetic testing and intensified screening, complete a psychosocial assessment, and undergo a clinical investigation consisting of a physical examination and collection of blood samples for prostate-specific antigen (PSA) measurement. Participants will then be referred to genetic counseling, and genetic testing will be offered to all patients in group 1 or 3. mpMRI is also obtained for those without a history of prostate cancer.

Those who proceed with genetic testing with undergo next-generation sequencing for a multigene panel analysis, comprised of 20 established cancer susceptibility genes: ATM, BRCA1, BRCA2, EPCAM, HOXB13, MLH1, MSH2, MSH6, PMS2, TP53, NBN, CHEK2, ATR, BRIP1, FANCA, GEN1, PALB2, PTEN, RAD51C, and RAD51D.

The authors noted, “We estimate that 80% to 85% of healthy men at risk of [prostate cancer] will not have any pathogenic variants identified by the 20-gene panel. Only these participants proceed to whole exome sequencing (WES). Literature suggests an additional 10% to harbor pathogenic variants in other genes. For the remaining 70% of participants without findings from the panel or WES, whole genome sequencing (WGS) and a transcriptome analysis are conducted to identify novel genomic alterations related to [prostate cancer].”

Ultimately, all clinical, genetic, and imaging results will be reviewed by a “risk board”, comprised of human geneticists, urologists, radiologists, and psychologists who will place patients into a risk group and provide recommendations for PSA or MRI follow-up or a prostate biopsy, if needed. In cohort 3, which includes patients with histologically confirmed prostate cancer and thus men likely to be already treated or under treatment, the investigators will seek to identify prostate cancer susceptibility genes and offer extended screening to their family members.

As of July 2025, 123 men had attended the prevention clinic, of whom 25 were placed into group 1 (family history of prostate cancer), 32 were placed into group 2 (germline variants; 13 with BRCA2, 12 with BRCA1, 3 with ATM, 1 with MLH1, 1 with CHEK2, 1 with MSH2, and 1 with MSH6), and 66 were placed into group 3 (of whom 22 were under active surveillance).

Although the initial recruitment results are promising, the authors note that larger sample sizes are still needed.

“The ProFam-Risk project represents an innovative step toward precision medicine in [prostate cancer] prevention, targeting men with familial or genetic predisposition,” the authors concluded. “By integrating genetic testing, mpMRI, and psychosocial assessment, the clinic addresses both clinical and psychological aspects of cancer risk. Despite promising first recruitment results, challenges such as limited sample size and cost effectiveness remain, warranting further research. The inclusion of other study locations is therefore essential.”

Final completion of the study is expected in February 2027.²

REFERENCES

1. Lakes J, Boschheidgen M, Antoch G, et al. Genetic Testing and Imaging in Men with Familial History or Genetic Predisposition of Prostate Cancer—Introducing the Prospective “ProFam-Risk” Study. Eur Urol Open Sci. 2026:84:13-21. doi:10.1016/j.euros.2025.12.018

2. Prostate Cancer Prevention Clinic for Men With Risk of Familial Prostate Cancer (ProFam-Risk). ClinicalTrials.gov. Last updated January 12, 2023. Accessed January 22, 2026. https://clinicaltrials.gov/study/NCT05681416