Prostate Cancer Prevention Clinic for Men With Risk of Familial Prostate Cancer

NCT05681416 | Not Yet Recruiting

• 1 other identifier: Studien-Nr.: 2022-2051
• Study Type: interventional
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief Summary

Secondary prevention of prostate cancer (PCa) is not standardized and high-risk groups at the time of diagnosis are not well defined. Hereditary susceptibility which is reported in about 10% of men is one important risk factor for PCa development but the absolute risk and clinical importance is fairly unknown. The population risk for developing PCa is estimated to be 11%. If men carry a mutation in BRCA2 or HOXB13, the lifetime risk is 2 to 10-fold increased. "ProFam-Risk" is a prospective cohort analysis not only to validate the known genetic risk scores but also to establish recommendations for follow of high risk populations based on a combination of clinical parameters, imaging (magnetic resonance imaging of the prostate), and genetic profile. Aim of this individualized recommendation is on the one hand to early detect PCa before developing of advanced disease and on the other hand to counsel men at low risk in order to prevent overdiagnosis and overtreatment. Overall, "ProFam-Risk" aims to create a best possible counseling and clinical care for men with familial risk to develop PCa. In this pilot study, about 100 men per year will be included for a total period of 3 years. In addition to the registration of clinical, imaging, and genetic information, liquids and tissue (if available) will be sampled for analysis in the above mentioned research questions.

Conditions

Prostate Cancer; Familial Prostate Cancer

Keywords

BRCA Mutation; Familial Prostate Cancer; Genetic Predisposition; Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Number and kind of Genetic Alterations and correlation with clinical and pathologic features

  mutation database for germline mutations and tumor mutations in familial PCA: Besides the mutation positive men (group 2), all will receive multigene panel analysis( ATM, BRCA1, BRCA2, EPCAM, HOXB13, MLH1, MSH2, MSH6, PMS2, TP53) and if negative, whole exome sequencing (WES), whole genome sequencing and transcriptome analyses The aim is to systematically and prospektively review genotype-phenotype correlations in the established candidate genes and to systematically correlate the clinical and pathologic features with the identified underlying genetic alterations. DNA for WES, WGS and RNA will be prepared by standard procedures, e.g. the FlexiGene DNA Kit (Qiagen) and PAXgene Blood RNA Kit (Qiagen)

  3-4 years

• Reduction in PCA-specific anxiety

  Assessment if men after risk assessment and genetic counseling will have a reduction in cancer-specific anxiety --\>Follow-ups with 3 measurement points (before, during, after counseling (T0, T1, T2)) The reduction in cancer-specific anxiety and improvement of personal risk perception and of personal control are tested by using a of variance- analytical model with repeated measures (T0, T1, T2) and the group factor "risk group" (high vs. intermediate vs. low) Quantitative questionnaire: • Prostate Cancer-specific anxiety (MAX-PC, modified scale 'prostate cancer anxiety', Lehmann 2006)

  3-4 years

Secondary Outcomes (1)

• Improvement of PCA-specific personal risk perception

  3-4 years

Study Arms (3)

Healthy men with familial risk

OTHER

≥ 2 first-degree relatives with PCA diagnosed at any age oder ≥ 1 first-degree relative with PCA diagnosed at the age \<60

Diagnostic Test: Panel sequencing, whole exome sequencing, whole genome sequencing

healthy men with genetic risk

OTHER

BRCA1/2 Germline mutation

Diagnostic Test: Panel sequencing, whole exome sequencing, whole genome sequencing

Men with PCA and genetic oder familial risk

OTHER

familial risk = ≥ 2 first-degree relatives with PCA diagnosed at any age oder ≥ 1 first-degree relative with PCA diagnosed at the age \<60 genetic risk= BRCA1/2 Germline mutation

Diagnostic Test: Panel sequencing, whole exome sequencing, whole genome sequencing

Interventions

Panel sequencing, whole exome sequencing, whole genome sequencing DIAGNOSTIC_TEST

Besides the mutation positive men (group 2), all will receive multigene panel analysis in a patient care setting and if negative, whole exome sequencing (WES), whole genome sequencing and transcriptome analyses. In PCA-affected men (group 3), additional mutational analysis will be performed on formalin-fixed paraffin embedded (FFPE) - and fresh frozen (FF) tumor tissue from biobanked radical prostatectomy specimens using FFPE panel analysis (like TruSightOncology 500) or WES if FF samples are available.

Also known as: mpMRI, psychometric tests, PSA Testing

Healthy men with familial risk; Men with PCA and genetic oder familial risk; healthy men with genetic risk

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Prostate cancer is only observed in men
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy men with familial risk ( ≥ 2 first-degree relatives with PCA diagnosed at any age oder ≥ 1 first-degree relative with PCA diagnosed at the age \<60)
• healthy men with genetic risk (BRCA1/2 Germline mutation)
• Men with PCA and genetic oder familial risk (familial risk = ≥ 2 first-degree relatives with PCA diagnosed at any age oder ≥ 1 first-degree relative with PCA diagnosed at the age \<60; genetic risk= BRCA1/2 Germline mutation)

You may not qualify if:

• \<18 years
• no consent

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead
• German Cancer Aid: collaborator

Related Publications (10)

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MeSH Terms

Conditions

Prostatic Neoplasms; Prostate cancer, familial; Genetic Predisposition to Disease

Interventions

Exome; Multiparametric Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Genome; Genetic Structures; Genetic Phenomena; Magnetic Resonance Imaging; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Peter Albers

  Department of Urology, University of Dusseldorf, Germany

  PRINCIPAL INVESTIGATOR

• Dagmar Wieczorek

  Humangenetics, University of Dusseldorf, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jale Lakes

CONTACT

+492118118110; jale.lakes@med.uni-duesseldorf.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: senior doctor at the department of urology

Model Details: Men with family history or already known BRCA1 or BRCA2 mutation and their family members will be offered a combined clinical, imaging and genetic profiling to tailor their risk to develop PCA. In addition, men with prostate cancer and positive family history will be offered genetic testing and mutational profiling of tumor tissue in order to exclude or detect hereditary cancer syndromes.

Study Record Dates

• First Submitted: November 29, 2022
• First Posted: January 12, 2023
• Study Start: February 1, 2023
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: January 12, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share