The PROFILE Feasibility Study: Targeted Screening of Men With a Family History of Prostate Cancer.
The PROFILE Feasibility Study: Targeted Screening of Men With a Family History of Prostate Cancer.
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DOI：
10.1634/theoncologist.2015-0336
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Eeles RA
中科院分区：
文献类型：
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作者：
Castro E;Mikropoulos C;Bancroft EK;Dadaev T;Goh C;Taylor N;Saunders E;Borley N;Keating D;Page EC;Saya S;Hazell S;Livni N;deSouza N;Neal D;Hamdy FC;Kumar P;Antoniou AC;Kote-Jarai Z;PROFILE Study Steering Committee;Eeles RA
为了改进筛查，需要更好地评估前列腺癌(PrCa)风险。这项初步研究探索了在有前列腺癌家族史(FH)的男性中进行单核苷酸多态分析的可行性，以调查在前列腺活检(PB)中检测到PrCA的可能性。目前的初步研究结果表明，对于患有FH的男性，PB是一种可行且安全的PrCa筛查方法。为了改进筛查，需要更好地评估个性化前列腺癌(PrCa)的风险。在一般人群中使用前列腺特异性抗原(PSA)水平进行筛查是有局限性的，目前并不提倡。大约100个常见的单核苷酸多态(SNPs)已经被确定与发生PrCA的风险相关。Profile试验性研究探索了在有PrCa家族史(FH)的男性中使用SNP图谱的可行性，以调查在前列腺活检(PB)中检测PrCa的可能性。这项先导性研究的主要目的是确定在FH患者中使用经直肠超声引导的经直肠外周血加或不加弥散加权磁共振成像(DW-MRI)进行PrCa筛查的安全性和可行性。第二个目的是评估SNP图谱作为筛查工具在这一人群中的潜在用途。共有100名年龄在40-69岁、FH为PrCA的男性接受了PB，无论他们的基线PSA水平如何。使用71个常见的PrCa易感等位基因计算每个参与者的多基因风险分数(PRSS)。我们将PB的疾病转归作为转归变量，并用单变量Logistic回归分析其与患者的PR、PSA水平和DW-MRI结果之间的关系。在100名男性中，25人被诊断为PrCA，其中12人(48%)有临床上的重大疾病。共发生4例不良反应，无死亡病例。PSA水平和研究开始时的年龄与PB的PrCa相关(p=.00037和p=.00004)。目前的初步研究结果表明，对于患有FH的男性，PB是一种可行且安全的PrCa筛查方法，因为发现的PrCa很高比例需要根治性治疗。收集PrCa风险SNPs的数据以评估其作为潜在筛查工具的联合效应是可行的。一项旨在检测统计相关性的更大规模的前瞻性研究正在进行中。对于有家族病史的男性，前列腺活检是一种可行且安全的前列腺癌筛查方法，可以检测出需要根治性治疗的前列腺癌的很高比例。使用前列腺癌风险单核苷酸多态计算多基因风险评分可能成为未来前列腺癌的潜在筛查工具。
A better assessment of prostate cancer (PrCa) risk is needed to improve screening. The PROFILE pilot study explored the feasibility of single nucleotide polymorphism profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH. A better assessment of individualized prostate cancer (PrCa) risk is needed to improve screening. The use of the prostate-specific antigen (PSA) level for screening in the general population has limitations and is not currently advocated. Approximately 100 common single nucleotide polymorphisms (SNPs) have been identified that are associated with the risk of developing PrCa. The PROFILE pilot study explored the feasibility of using SNP profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The primary aim of this pilot study was to determine the safety and feasibility of PrCa screening using transrectal ultrasound-guided PB with or without diffusion-weighted magnetic resonance imaging (DW-MRI) in men with a FH. A secondary aim was to evaluate the potential use of SNP profiling as a screening tool in this population. A total of 100 men aged 40–69 years with a FH of PrCa underwent PB, regardless of their baseline PSA level. Polygenic risk scores (PRSs) were calculated for each participant using 71 common PrCa susceptibility alleles. We treated the disease outcome at PB as the outcome variable and evaluated its associations with the PRS, PSA level, and DW-MRI findings using univariate logistic regression. Of the 100 men, 25 were diagnosed with PrCa, of whom 12 (48%) had clinically significant disease. Four adverse events occurred and no deaths. The PSA level and age at study entry were associated with PrCa at PB (p = .00037 and p = .00004, respectively). The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH, with a high proportion of PrCa identified requiring radical treatment. It is feasible to collect data on PrCa-risk SNPs to evaluate their combined effect as a potential screening tool. A larger prospective study powered to detect statistical associations is in progress. Prostate biopsy is a feasible and safe approach to prostate cancer screening in men with a family history and detects a high proportion of prostate cancer that needs radical treatment. Calculating a polygenic risk score using prostate cancer risk single nucleotide polymorphisms could be a potential future screening tool for prostate cancer.