局部前列腺癌的基因组检测可以识别出具有侵袭性疾病的非裔美国人亚群。
Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease.
机构信息
H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Veracyte Inc, South San Francisco, CA, USA.
出版信息
J Natl Cancer Inst. 2022 Dec 8;114(12):1656-1664. doi: 10.1093/jnci/djac162.
BACKGROUND
Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting.
METHODS
This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score.
RESULTS
The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes.
CONCLUSIONS
Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.
背景
个性化基因组分类器通过鉴定最具侵袭性的前列腺癌（PCa）亚群，改变了 PCa 的治疗管理模式。然而，迄今为止，在前瞻性研究中，基因组分类器在风险分类方面对非裔美国男性的表现仍存在不足。
方法
这是一项针对国家综合癌症网络低危和中危 PCa 的 Decipher 基因组分类器的前瞻性研究。符合条件的非裔美国男性与非裔美国男性相匹配。对诊断性活检标本进行处理，以估计 Decipher 评分。在 NCT02723734 前瞻性研究中，对入组样本进行分析，以确定传统临床风险分类器与 Decipher 评分之间的基因组再分类风险（GrR）。
结果
最终分析纳入了具有完整基因组信息的 226 例临床平衡队列患者（113 例非裔美国男性和 113 例非裔美国男性）。具有国家综合癌症网络低危（18.2%）和有利中危（37.8%）PCa 的非裔美国男性中，有更高比例的男性具有较高的 Decipher 评分。自我认定的非裔美国男性发生 GrR 的可能性是非裔美国男性的两倍（相对风险 [RR] = 2.23，95%置信区间 [CI] = 1.02 至 4.90；P = 0.04）。在基于祖先的种族模型中，我们一致验证了非裔美国男性再分类风险更高（RR = 5.26，95%CI = 1.66 至 16.63；P = 0.004）。GrR 与非 GrR 肿瘤的种族分层分析也揭示了这些肿瘤亚型的分子差异。
结论
将基因组分类器与基于临床的风险分类相结合，有助于识别出患有局限性 PCa 的非裔美国男性亚群，这些患者具有早期转移性疾病的高基因组风险。重要的是要识别和适当分层具有侵袭性疾病的非裔美国男性亚群，这些患者可能受益于更有针对性的干预措施。
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