A Targeted Methylation-Based Multicancer Early Detection Blood Test Preferentially Detects High-Grade Prostate Cancer...

Area of Science:

• Oncology
• Genomics
• Biomarker Discovery

Background:

• Indolent prostate cancer (PCa) is common in adults aged 50-79, the target demographic for blood-based multicancer early detection (MCED) tests.
• Evaluating the detectability of PCa by MCED tests is crucial for their clinical utility.

Purpose of the Study:

• To assess the detectability of prostate cancer (PCa) using a targeted methylation-based multicancer early detection (MCED) test.
• To examine PCa detection rates based on Gleason grade group (GG) and clinical stage.
• To analyze the association between detection status, tumor methylated fraction (TMeF), and overall survival (OS).

Main Methods:

• Analysis of data from substudy 3 of the Circulating Cell-Free Genome Atlas (CCGA) and the PATHFINDER studies.
• Assessment of MCED test performance across different Gleason grade groups (GG1-5) and clinical stages (I-IV).
• Correlation of test detection status with tumor methylated fraction (TMeF) and comparison of overall survival (OS) with SEER data.

Main Results:

• The MCED test demonstrated a PCa sensitivity of 11.2% in the CCGA study.
• Detection rates varied significantly by grade and stage, with higher sensitivity for high-grade (GG4/5: 31.9%) and advanced-stage (Stage IV: 81.5%) cancers.
• Detected cases had a higher median TMeF, and nondetected cases showed better OS, while detected cases had similar survival compared to expected.
• Similar performance was observed in the PATHFINDER study, with no detection of low-grade (GG1/2) or early-stage (Stage I/II) PCa.

Conclusions:

• The evaluated MCED test preferentially detects high-grade, clinically significant prostate cancer.
• Its use in population-based screening is unlikely to worsen the overdiagnosis of indolent PCa.
• The test shows potential as a complementary tool in prostate cancer screening strategies.