摘要2605:利用多参数MRI (mpMRI)研究前列腺癌(PCa)高危遗传男性的自然病史

F. Karzai, A. Couvillon, Y. McKinney, Katherine Lee-Wisdom, P. Choyke, V. Giri, T. Morgan, Heather H. Cheng, M. Merino, P. Pinto, B. Turkbey, W. Dahut
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One prt was upstaged on radical prostatectomy (RP). Conclusions: We found mpMRI-based PCa screening in men with high-risk gene mutations, especially DDR genes, is feasible and can be used to identify clinically significant PCa and monitor for disease progression. Future guidelines should consider age, mutation specificity and mpMRI. Accrual and correlative studies (biomarkers, PBMCs) are on-going. Citation Format: Fatima Karzai, Anna Couvillon, Yolanda McKinney, Katherine Lee-Wisdom, Peter L. Choyke, Veda N. Giri, Todd M. Morgan, Heather H. Cheng, Maria J. Merino, Peter A. Pinto, Baris Turkbey, William L. Dahut. A natural history study of men with high-risk genetics for prostate cancer (PCa) using multiparametric MRI (mpMRI) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. 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引用次数: 0

摘要

简介:了解分子遗传学在前列腺癌提供洞察疾病进展和治疗。对于PCa相关基因,特别是DNA损伤修复(DDR)中存在高危种系致病/可能致病变异的男性,PCa的发展情况知之甚少。mpMRI可以定位和检测该人群的前列腺癌病变。我们正在对男性参与者(prts)进行一项多中心自然史研究,这些参与者记录了BRCA1、BRCA2、MLH1、MSH2、MSH6、PMS2、EPCAM、HOXB13、ATM、NBN、TP53、CHEK2、PALB2、RAD51D、BRIP1或FANCA的种系变异,但没有使用mpMRI (NCT03805919)进行PCa诊断。方法:多达500名30-75岁(y/o)的男性将在基线和每2年(年)进行mpMRI评估。每隔12个月随访一次,以确定PSA、PCa诊断和/或疾病/生存状态,直至死亡。前列腺活检指征:30 - 49岁,PSA >2.0;50 - 75岁和/或PIRADS 3+ MRI病变>2.5 ng/mL或临床判断。获得的组织将进行完整的转录组分析。结果:100例患者入组。平均年龄为47岁。研究中PSA中位数为0.87 (0.16-10.05 ng/mL)。中位PSA密度为0.029。基因突变为BRCA2(40%)、BRCA1(33%)、MSH2(9%)和CHEK2(4%)。ATM、HOXB13、MLH1、MSH6、PMS2和EPCAM的突变≤3%。未观察到明显的ae。96例患者中,25例(26%)有活检指征[PIRADS 4级病变:16例(64%),PIRADS 3级病变:4例(16%),PSA升高:6例(24%),或临床指征1例(4%)]。22例行前列腺活检,6例诊断为前列腺癌。一名患者在根治性前列腺切除术(RP)中被抢镜。结论:我们发现基于mpmri的前列腺癌筛查在高危基因突变的男性,特别是DDR基因,是可行的,可用于识别临床显著的前列腺癌和监测疾病进展。未来的指南应考虑年龄、突变特异性和mpMRI。应计性和相关研究(生物标志物、PBMCs)正在进行中。引文格式:Fatima Karzai, Anna Couvillon, Yolanda McKinney, Katherine Lee-Wisdom, Peter L. Choyke, Veda N. Giri, Todd M. Morgan, Heather H. Cheng, Maria J. Merino, Peter A. Pinto, Baris Turkbey, William L. Dahut。使用多参数磁共振成像(mpMRI)对前列腺癌(PCa)高危遗传男性的自然史研究[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2605。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Abstract 2605: A natural history study of men with high-risk genetics for prostate cancer (PCa) using multiparametric MRI (mpMRI)
Introduction: The understanding of molecular genetics in PCa provides insight into disease progression and treatment. Less is known about PCa development in men with known high-risk germline pathogenic/likely pathogenic variants in PCa related genes, particularly DNA damage repair (DDR). mpMRI can localize and detect PCa lesions in this population. We are conducting a multicenter natural history study of male participants (prts) with documented germline variant(s) in BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, EPCAM, HOXB13, ATM, NBN, TP53, CHEK2, PALB2, RAD51D, BRIP1, or FANCA who do not have a PCa diagnosis using mpMRI (NCT03805919). Methods: Up to 500 men, 30-75 years old (y/o) will undergo mpMRI evaluation at baseline and every 2 years (yrs). Prts are followed at 12-mo intervals to determine PSA, PCa diagnosis, and/or disease/survival status until death. Indication for prostate biopsy includes PSA >2.0 for 30 - 49 y/o; >2.5 ng/mL for 50 - 75 y/o and/or PIRADS 3+ MRI lesion or clinical discretion. Tissue obtained will undergo full transcriptome analysis. Results: 100 prts have enrolled. Median age is 47 y/o. Median on-study PSA is 0.87 (0.16-10.05 ng/mL). Median PSA density is 0.029. Gene mutations are BRCA2 (40%), BRCA1 (33%), MSH2 (9%), and CHEK2 (4%). Mutations in ATM, HOXB13, MLH1, MSH6, PMS2, and EPCAM are ≤3%. No significant AEs have been observed. Of 96 prts, 25 (26%), had indication for biopsy [PIRADS 4 lesion: 16 (64%), PIRADS 3 lesion: 4 (16%), elevated PSA: 6 (24%), or clinical indication 1: (4%)]. 22 prostate biopsies were performed and 6 prts were diagnosed with PCa. One prt was upstaged on radical prostatectomy (RP). Conclusions: We found mpMRI-based PCa screening in men with high-risk gene mutations, especially DDR genes, is feasible and can be used to identify clinically significant PCa and monitor for disease progression. Future guidelines should consider age, mutation specificity and mpMRI. Accrual and correlative studies (biomarkers, PBMCs) are on-going. Citation Format: Fatima Karzai, Anna Couvillon, Yolanda McKinney, Katherine Lee-Wisdom, Peter L. Choyke, Veda N. Giri, Todd M. Morgan, Heather H. Cheng, Maria J. Merino, Peter A. Pinto, Baris Turkbey, William L. Dahut. A natural history study of men with high-risk genetics for prostate cancer (PCa) using multiparametric MRI (mpMRI) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2605.
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