A Targeted Methylation-Based Multicancer Early Detection Blood Test Preferentially Detects High-Grade Prostate Cancer While Minimizing Overdiagnosis of Indolent Disease.

IF 5.3 2区医学 Q1 ONCOLOGY JCO precision oncology Pub Date : 2024-08-01 DOI:10.1200/PO.24.00269

Brandon A Mahal, Matthew Margolis, Earl Hubbell, Cheng Chen, Jeffrey M Venstrom, John Abran, Jordan J Kartlitz, Alexander W Wyatt, Eric A Klein

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Abstract

Purpose: Indolent prostate cancer (PCa) is prevalent in the intended use population (adults age 50-79 years) for blood-based multicancer early detection (MCED) tests. We examined the detectability of PCa by a clinically validated, targeted methylation-based MCED test.

Methods: Detectability by Gleason grade group (GG), clinical stage, association of detection status with tumor methylated fraction (TMeF), and overall survival (OS) were assessed in substudy 3 of Circulating Cell-Free Genome Atlas (CCGA; ClinicalTrials.gov identifier: NCT02889978) and PATHFINDER (ClinicalTrials.gov identifier: NCT04241796) studies.

Results: Test sensitivity for PCa in substudy 3 of CCGA was 11.2% (47/420). The test detected 0 (0%) of 58 low-grade (GG1), 3 (1.9%) of 157 favorable intermediate-grade (GG2), 4 (5.1%) of 78 unfavorable intermediate-grade (GG3), and 36 (31.9%) of 113 high-grade (GG4 and 5) cancers and 3 (3.2%) of 95 stage I, 11 (4.7%) of 235 stage II, 7 (14.9%) of 47 stage III, and 22 (81.5%) of 27 stage IV cases. The median TMeF was higher for detected than nondetected cases (2,106.0 parts per million [PPM]; IQR, 349.8-24,376.3 v 24.4 PPM; IQR, 17.8-38.5; P < .05). Nondetected cases had better OS (P < .05; hazard ratio [HR], 0.263 [95% CI, 0.104 to 0.533]) and detected cases had similar survival (P = .2; HR, 0.672 [95% CI, 0.323 to 1.21]) compared with SEER adjusted for age, GG, and stage. Performance was similar in PATHFINDER, with no detected GG1/2 (0/13) or stage I/II (0/16) cases.

Conclusion: This MCED test preferentially detects high-grade, clinically significant PCa. Use in population-based screening programs in addition to standard-of-care screening is unlikely to exacerbate overdiagnosis of indolent PCa.

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一种基于目标甲基化的多癌症早期检测血液检验能优先检测高级别前列腺癌，同时最大限度地减少对隐匿性疾病的过度诊断。

目的：在基于血液的多癌症早期检测（MCED）试验的预期使用人群（50-79 岁的成年人）中，多见偶发性前列腺癌（PCa）。我们研究了一种经过临床验证的、基于甲基化靶向的 MCED 检验对 PCa 的检测能力：方法：在循环无细胞基因组图谱（CCGA；ClinicalTrials.gov identifier：NCT02889978）和PATHFINDER（ClinicalTrials.gov identifier：NCT04241796）研究的子研究3中，按格里森分级组（GG）、临床分期、检测状态与肿瘤甲基化率（TMeF）的关系以及总生存率（OS）评估了检测能力：CCGA子研究3的PCa检测灵敏度为11.2%（47/420）。该检测发现了 58 例低度癌（GG1）中的 0 例（0%）、157 例中度癌（GG2）中的 3 例（1.9%）、78 例中度癌（GG3）中的 4 例（5.1%）和 113 例高级别癌（GG4 和 5）中的 36 例（31.9%），以及 95 例 I 期癌中的 3 例（3.2%）、235 例 II 期癌中的 11 例（4.7%）、47 例 III 期癌中的 7 例（14.9%）和 27 例 IV 期癌中的 22 例（81.5%）。检测到的病例的 TMeF 中值高于未检测到的病例（百万分之 2,106.0 [PPM]；IQR，349.8-24,376.3 v 24.4 PPM；IQR，17.8-38.5；P < .05）。与根据年龄、GG 和分期调整的 SEER 相比，未检出病例的 OS 更好（P < .05；危险比 [HR]，0.263 [95% CI，0.104 至 0.533]），检出病例的生存率相似（P = .2；HR，0.672 [95% CI，0.323 至 1.21]）。在PATHFINDER中的表现类似，没有发现GG1/2（0/13）或I/II期（0/16）病例：结论：这种 MCED 检验能优先检测出高级别、有临床意义的 PCa。结论：该MCED检验能优先检测出高级别、有临床意义的PCa。在人群筛查项目中，除了标准治疗筛查外，使用该检验不太可能加剧对不太严重的PCa的过度诊断。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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