Evaluation of a Multimodal Strategy for Early Diagnosis of Men at High Genetic Risk of Prostate Cancer
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 入组人数
- 880
- 主要终点
- Rate of men diagnosed with PC and aggressive PC (ISUP>3 or T2c-T3)
研究概览
简要总结
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.
详细描述
Hereditary prostate cancer (HPC) has been defined by strict clinical criteria and represents 5% of all newly diagnosed prostate cancers (PC). Inherited predisposition to PC is also genetically determined by the presence of a deleterious mutation of DNA repair genes related to breast/ovarian cancers (BRCA2, BRCA1, ATM,...) or of PC specific variants (HOXB13 and 8q24-CASC19).
According typology of genetic risk, predisposition exposes to an earlier age of onset or a more aggressive form of the disease, increasing the risk of death from this cancer.
Currently, abnormal digital rectal examination (DRE) and PSA level above 4ng/mL are validated as an indication for performing a MRI and prostate biopsies to establish PC diagnosis in its frequent sporadic form. Recommendations for the management and the mitigation of PC risk with early screening just emerge for BRCA2 mutation carriers.
The unaffected relatives from these HPC families and the carriers of these mutations are potentially at higher risk of PC and need a dedicated screening procedure.
This project is based on our experience and the results from the international IMPACT study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Rate of men diagnosed with PC and aggressive PC (ISUP>3 or T2c-T3)
时间窗: Through study completion, up to 5 years
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.
次要结局
- 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 adverse events related to the diagnostic procedures(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)