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

NCT05333432 | Withdrawn

• 1 other identifier: APHP210359
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

Urology; Oncogenetics; Radiology

Outcome Measures

Primary Outcomes (1)

• Rate of men diagnosed with PC and aggressive PC (ISUP>3 or T2c-T3)

  ISUP grade group 2 or higher PC are detected by prostate biopsies which are performed in case of abnormal DRE, PSA \> 3ng/mL or PIRADS-V2 \> 2 on mpMRI. DRE examination, PSA test and mpMRI examination are annual. Timepoint is at the end of the study.

  Through study completion, up to 5 years

Secondary Outcomes (5)

• Rate of men diagnosed with PC according aggressiveness classification (ISUP and TNM) in each genetic group

  Through study completion, up to 5 years

• Rate of performed prostatic biopsies

  Through study completion, up to 5 years

• Rate of men diagnosed with PC using mpMRI with or without perfusion sequence

  Through study completion, up to 5 years

• Rate of men diagnosed with PC according to the type of deleterious mutations, and genetic background/environment modulators of risk

  Through study completion, up to 5 years

• Rate of adverse events related to the diagnostic procedures

  Through study completion, up to 5 years

Study Arms (1)

Men at high genetic risk of prostate cancer

OTHER

Cohort of unaffected men from 40 to 70 years olds with high 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 or a gene specific to PC.

Procedure: Multiparameric MRI with injection

Interventions

Multiparameric MRI with injection PROCEDURE

Participants have a prostate multiparametric MRI with gadolinium injection (T2, diffusion and perfusion sequences) every year. PIRADS-V2 is used as decisional endpoint, and subjective score LIKERT as secondary analysis. To compute sensivity and specificity, we consider LIKERT as suspicious and/or malignant (PIRADS-V2 = 3, 4 or 5) as positive.

Men at high genetic risk of prostate cancer

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• National Cancer Institute, France: collaborator

Related Publications (2)

• Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, Collaco-Moraes Y, Ward K, Hindley RG, Freeman A, Kirkham AP, Oldroyd R, Parker C, Emberton M; PROMIS study group. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017 Feb 25;389(10071):815-822. doi: 10.1016/S0140-6736(16)32401-1. Epub 2017 Jan 20.

  PMID: 28110982 BACKGROUND

• Page EC, Bancroft EK, Brook MN, Assel M, Hassan Al Battat M, Thomas S, Taylor N, Chamberlain A, Pope J, Raghallaigh HN, Evans DG, Rothwell J, Maehle L, Grindedal EM, James P, Mascarenhas L, McKinley J, Side L, Thomas T, van Asperen C, Vasen H, Kiemeney LA, Ringelberg J, Jensen TD, Osther PJS, Helfand BT, Genova E, Oldenburg RA, Cybulski C, Wokolorczyk D, Ong KR, Huber C, Lam J, Taylor L, Salinas M, Feliubadalo L, Oosterwijk JC, van Zelst-Stams W, Cook J, Rosario DJ, Domchek S, Powers J, Buys S, O'Toole K, Ausems MGEM, Schmutzler RK, Rhiem K, Izatt L, Tripathi V, Teixeira MR, Cardoso M, Foulkes WD, Aprikian A, van Randeraad H, Davidson R, Longmuir M, Ruijs MWG, Helderman van den Enden ATJM, Adank M, Williams R, Andrews L, Murphy DG, Halliday D, Walker L, Liljegren A, Carlsson S, Azzabi A, Jobson I, Morton C, Shackleton K, Snape K, Hanson H, Harris M, Tischkowitz M, Taylor A, Kirk J, Susman R, Chen-Shtoyerman R, Spigelman A, Pachter N, Ahmed M, Ramon Y Cajal T, Zgajnar J, Brewer C, Gadea N, Brady AF, van Os T, Gallagher D, Johannsson O, Donaldson A, Barwell J, Nicolai N, Friedman E, Obeid E, Greenhalgh L, Murthy V, Copakova L, Saya S, McGrath J, Cooke P, Ronlund K, Richardson K, Henderson A, Teo SH, Arun B, Kast K, Dias A, Aaronson NK, Ardern-Jones A, Bangma CH, Castro E, Dearnaley D, Eccles DM, Tricker K, Eyfjord J, Falconer A, Foster C, Gronberg H, Hamdy FC, Stefansdottir V, Khoo V, Lindeman GJ, Lubinski J, Axcrona K, Mikropoulos C, Mitra A, Moynihan C, Rennert G, Suri M, Wilson P, Dudderidge T; IMPACT Study Collaborators; Offman J, Kote-Jarai Z, Vickers A, Lilja H, Eeles RA. Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers. Eur Urol. 2019 Dec;76(6):831-842. doi: 10.1016/j.eururo.2019.08.019. Epub 2019 Sep 16.

  PMID: 31537406 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Injections

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Pierre MONGIAT-ARTUS, PUPH

  Department of Urology - Hôpital Saint Louis - APHP Sorbonne Université

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a non-comparative multicenter prospective cohort. It follows annually two population groups according to their initial panel of PC predisposing genes. Therefore, it is not randomised.The follow-up is the same for all the participants: it is non-comparative. Participant is benefiting of a substantial and close medical surveillance during 3 years: each participant undergoes 4 annual mpRMI of which 2 are added by the research.

Study Record Dates

• First Submitted: April 11, 2022
• First Posted: April 19, 2022
• Study Start: January 1, 2026
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: June 25, 2025

Record last verified: 2025-06