Response to Haiman, Kote-Jarai, Darst et al.
Response to Haiman, Kote-Jarai, Darst et al.
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对 Haiman、Kote-Jarai、Darst 等人的回应
DOI：
10.1093/jnci/djad006
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Hauger,RichardL
中科院分区：
文献类型：
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作者：
Seibert,TylerM;Pagadala,MeghanaS;Lynch,Julie;Karunamuni,Roshan;Carter,Hannah;Rose,BrentS;Hauger,RichardL
我们感谢作者对我们工作的兴趣以及他们对前列腺癌（PCa）遗传学的重要贡献。作者对我们强调致命的PCa表示担忧。我们纳入了3个终点：PCa发生率、转移性PCa和致死性PCa。每个都是临床相关的。我们使用考克斯回归来评估每个终点发生时的年龄。这种方法在流行病学和肿瘤学中很常见，在病例对照状态方面比逻辑回归有很大的优势。例如，最初诊断为Gleason 7 PCa的男性可能后来发展为转移性PCa或可能具有惰性病程。同样，在52岁时被诊断患有Gleason 6 PCa的男性在其一生中很可能发展出临床显著的PCa。生存分析适当地考虑了这些可能性，允许在分析早期检测策略旨在避免的关键终点（转移性或致命性PCa）时纳入早期PCa诊断，我们同意目前的多基因评分并不特异于侵袭性疾病，并相应地提醒读者。男性应被告知前列腺特异性抗原检测假阳性，过度诊断和过度治疗。我们和其他人正致力于开发特异于致命PCa的标记物和诊断测试。与此同时，我们注意到应使用现有的工具来缓解筛查危害，包括磁共振成像，血液或尿液检查以及对可诊断风险PCa的主动监测。
We thank the writers for their interest in our work and for their important contributions to prostate cancer (PCa) genetics. The writers express concern about our emphasis on lethal PCa. We included 3 endpoints: PCa incidence, metastatic PCa, and fatal PCa. Each is clinically relevant. We used Cox regression to evaluate age at occurrence for each endpoint. This approach—common in epidemiology and oncology—offers substantial advantages over logistic regression for case-control status. For example, a man initially diagnosed with Gleason 7 PCa may later develop metastatic PCa or may have an indolent course. Likewise, a man diagnosed with Gleason 6 PCa at age 52 years could very well develop clinically significant PCa in his lifetime. Survival analyses appropriately account for these possibilities, permitting inclusion of early PCa diagnoses in analyses of critical endpoints that early detection strategies intend to avoid (metastatic or fatal PCa).We agree that current polygenic scores are not specific for aggressive disease and have cautioned readers accordingly. Men should be counseled about false-positive prostate-specific antigen tests, overdiagnosis, and overtreatment. We and others are working to develop markers and diagnostic tests specific for lethal PCa. Meanwhile, we noted that existing tools for mitigation of screening harms should be used, including magnetic resonance imaging, blood or urine tests, and active surveillance of favorable-risk PCa.