Evaluation of a Multimodal Strategy for Early Diagnosis of Men at High Genetic Risk of Prostate Cancer

Inherited predisposition to prostate cancer (PC) has been defined by strict clinical criteria or by genetic profile determined by the presence of a deleterious mutation of deoxyribonucleic acid (DNA) repair genes related to breast/ovarian cancers (such as BRCA2, BRCA1) or by PC specific variants (HOXB13 and 8q24CASC19). But currently, recommendations for management and mitigation of PC risk with early screening just emerge for BRCA2 mutation carriers. Our study compares a PC screening strategy based on an annual prostate specific antigen (PSA) test and a clinical examination to a strategy that also includes an annual multiparametric magnetic resonance imaging (mpMRI). It focus not only on 440 unaffected men carrying the BRCA2 mutation, but also on 440 unaffected men member of hereditary PC families with an unidentified mutation or carriers of a mutation of another gene that predisposes to PC, for a total number of participants included of 880. This project estimates the benefits and inconveniences to extend the proposed early diagnosis procedure from unaffected men with BRCA2 mutation to all unaffected men meeting criteria of an inherited predisposition. It should allow to diagnose PC at a more curable stage, and to establish national recommendations for the management of men with high genetic risk of PC useful in clinical routine, depending on typology of the genetic risk. This project aims to efficiently diagnose them, without performing unnecessary biopsies, at curable stage of the disease. It should reduce their risk of death from this cancer known to be of bad prognosis at an advanced stage.

Sex

Male

Minimum age

40 Years

Maximum age

70 Years

Inclusion Criteria:

* Unaffected men at high genetic risk of prostate cancer (PC) defined as being a member from a family that meets hereditary PC criteria or by carrying a mutation of a DNA repair gene (BRCA1 / BRCA2 / CDH1 / MLH1 / MSH2 / MSH6 / PALB2 / PTEN / RAD51C / RAD51D / TP53 / ATM / BARD1 / BLM / BRIP1 / CHEK2 / MRE11A / MLH3 / NBN / RAD50 / STK11) or a gene specific to PC (HOXB13 / 8q24-CASC19)
* Aged between 40 and 70 years old
* Written informed consent signed by the participant
* Affiliated to the social security system

Exclusion Criteria:

* Contraindication for MRI (any foreign metallic bodies: cardiac implantable electronic device (CIED) such as pacemakers, implantable cardioverter defibrillators (ICDs) etc., metallic intraocular foreign bodies, implantable neurostimulation systems, cochlear implants/ear implant, drug infusion pumps (insulin delivery, analgesic drugs, or chemotherapy pumps): If possible, the participant has to remove the device. catheters with metallic components (Swan-Ganz catheter), metallic fragments such as bullets, shotgun pellets, and metal shrapnel , cerebral artery aneurysm clips, magnetic dental implants, tissue expander, artificial limb, hearing aid , piercing, clostrophobia, contrast agents allergy or any other contraindication to contrast agents and to their excipients)
* Treatment with a drug that changes PSA level such as 5 alpha reductase inhibitors (dutastéride, finasteride),
* Prostatic biopsy during the last 2 years, or other progressive cancer or co-morbidities threatening survival at 10 years
* Participant under tutorship or / guardianship, and incapable to give informed consent
* Participation to another interventional clinical trial

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