一种基于靶向甲基化的多癌种早期检测血液检测，在优先检测高级别前列腺癌的同时，最大限度地减少了惰性疾病的过度诊断。
A Targeted Methylation-Based Multicancer Early Detection Blood Test Preferentially Detects High-Grade Prostate Cancer While Minimizing Overdiagnosis of Indolent Disease.
机构信息
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL.
GRAIL, Inc, Menlo Park, CA.
出版信息
JCO Precis Oncol. 2024 Aug;8:e2400269. doi: 10.1200/PO.24.00269.
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 24.4 PPM; IQR, 17.8-38.5; < .05). Nondetected cases had better OS ( < .05; hazard ratio [HR], 0.263 [95% CI, 0.104 to 0.533]) and detected cases had similar survival ( = .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.
目的
血液多癌种早期检测（MCED）试验的目标人群为年龄在 50-79 岁的成年人，其中包括惰性前列腺癌（PCa）。我们研究了一种经过临床验证的靶向甲基化 MCED 试验对 PCa 的检测能力。
方法
在 Circulating Cell-Free Genome Atlas（CCGA；ClinicalTrials.gov 标识符：NCT02889978）和 PATHFINDER（ClinicalTrials.gov 标识符：NCT04241796）研究的亚研究 3 中，根据 Gleason 分级组（GG）、临床分期、检测状态与肿瘤甲基化分数（TMeF）的关系以及总生存（OS）评估检测能力。
结果
CCGA 亚研究 3 中，该检测对 PCa 的敏感度为 11.2%（47/420）。该检测未检出 58 例低级别（GG1）肿瘤中的 0 例，157 例中级别（GG2）肿瘤中的 3 例，78 例中高级别（GG3）肿瘤中的 4 例，113 例高级别（GG4 和 GG5）肿瘤中的 36 例，95 例 I 期肿瘤中的 3 例，235 例 II 期肿瘤中的 11 例，47 例 III 期肿瘤中的 7 例和 27 例 IV 期肿瘤中的 22 例。与未检出病例相比，检出病例的 TMeF 中位数更高（2106.0 个 ppm；四分位距[IQR]，349.8-24376.3 24.4 ppm；IQR，17.8-38.5；<0.05）。与 SEER 相比，未检出病例的 OS 更好（<0.05；风险比[HR]，0.263[95%CI，0.104-0.533]），检出病例的生存情况相似（=0.2；HR，0.672[95%CI，0.323-1.21]）。该检测的性能在 PATHFINDER 中相似，未检出 GG1/2（0/13）或 I/II 期（0/16）病例。
结论
该 MCED 试验可优先检测高级别、有临床意义的 PCa。将其与标准护理筛查联合用于基于人群的筛查计划不太可能加重对惰性 PCa 的过度诊断。
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