Prostate Cancer Screening Among Men With High Risk Genetic Predisposition

Study Overview
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Brief Summary
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This will be a prospective diagnostic trial of screening for prostate cancer among men with genetic predisposition.

Detailed Description
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This will be a prospective diagnostic trial of screening for prostate cancer among men with genetic predisposition. The target population is males (40-70 year old) carrying a BRCA1 and/or BRCA2 germ line mutation. They will be identified via our Genetic counseling unit. All men after signing an informed consent will undergo the following tests: PSA, free to total PSA, MRI of prostate and prostate biopsy. The primary endpoint will be to estimate the prevalence, stage and grade of prostate cancer in this population. Additionally, the study aims to estimate the impact of these germ line mutations on benign prostatic hyperplasia. Furthermore, this study aims to create a bio-bank of tissue, urine and serum of this unique cohort for future investigations. Finally, this study will identify an inception cohort for future interventional studies of primary and secondary prevention.

Official Title
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Personalized Prostate Cancer Screening Among Men With High Risk Genetic Predisposition- a Prospective Cohort Study

Conditions
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BRCA1 Syndrome, BRCA2 Syndrome, Lynch Syndrome

Intervention / Treatment
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* Other: PSA
* Other: IPSS questionnaire
* Other: DRE (Digital Rectal Examination )
* Other: urine flow and residual
* Procedure: a multiparametric prostate MRI
* Procedure: trans-rectal ultra-sound guided prostate biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male carrier of mutation in BRCA 1\2 or germ-line mutations in the MMR genes (MLH1, MSH2 , MSH6 or PMS2). WHO performance status 0-2 (Appendix 2) Absence of any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow-up schedule. Individuals that cannot undergo the MRI exam due to high creatinine level or claustrophobic will be disc loud from the MRI part. Informed written consent must be sought according to ICH/EU GCP, before subject registration. Exclusion Criteria: Previous cancer with a terminal prognosis of less than five years. Previous prostate cancer

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: screening tests<br>The screening will include: DRE, PSA , a multiparametric prostate MRI and a trans-rectal ultra-sound guided prostate biopsy/ MRI-US fusion , IPSS questionnaire, trans-rectal US assessment of prostate size, urine flow and residual. | Other: PSA<br>* PSA. Serum & plasma will be stored for future investigations<br>Other: IPSS questionnaire<br>* the validated International Prostate Symptom Score<br>Other: DRE (Digital Rectal Examination )<br>* physical examination for the prostate gland<br>Other: urine flow and residual<br>* The post void residual will be recorded by using ultrasound. Creatinine level will be checked.<br>Procedure: a multiparametric prostate MRI<br>* The MRI will be reported on a 5 point Likert Scale<br>Procedure: trans-rectal ultra-sound guided prostate biopsy<br>* 12 core Trans-rectal prostatic biopsy for diagnostic purposes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence, stage and pathology of screen-detected prostate cancer in BRCA1/BRCA2 founder mutation carriers and Lynch mutation carriers |  | within 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of different screening tests (PSA, free to total PSA, prostate MRI) in detecting prostate cancer among men with genetic predispositions. |  | within 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, BRCA1 Syndrome, BRCA germ-line mutation, Lynch syndrome, BRCA2 Syndrome