JCO Precis Oncol. 2026 Mar;10(3):e2500725. doi: 10.1200/PO-25-00725. Epub 2026 Mar 12.
ABSTRACT
PURPOSE: A multicancer early detection (MCED) test was developed and validated in the case-control Circulating Cell-free Genome Atlas (CCGA) study (ClinicalTrials.gov identifier: NCT02889978). Previous analysis of the second (cross-validation) CCGA substudy identified prognostic value of cancer signal detection by the MCED test with 3-year follow-up. Here, we evaluated the prognostic value of a cancer signal detected (CSD) result in the third (validation) CCGA substudy (CCGA3) using an updated statistical methodology with 5-year follow-up.
METHODS: CCGA3 participants with confirmed cancer were followed for up to 5 years; overall survival was stratified by MCED test result (CSD or no CSD [NCSD]). Observed survival was compared with the expected survival of a reference population calculated from Surveillance, Epidemiology, and End Results data matched to clinical characteristics (age, sex, cancer type, and stage) in each signal detection group.
RESULTS: Of 2,513 participants with stageable, invasive cancer, 792 (31.5%) died and 1,683 (67.0%) were confirmed alive at follow-up, with 38 (1.5%) lost to follow-up. CSD rates were higher in participants who died during follow-up compared with those alive (85% v 34%). Overall observed survival versus expected survival was similar for CSD (43% observed v 40% expected) and NCSD (88% observed v 81% expected) groups. For NCSD, hazard ratios (HRs) were more favorable (<1) relative to the matched reference population at all stages (P < .0001); for CSD, HRs were <1 at stages III to IV (P < .0001) and ≅1 at stages I to II (P > .4).
CONCLUSION: CSD cancers had long-term survival similar to expectations, even in early stages, indicating that CSD early-stage cancers are unlikely to be more micrometastatic and lethal than cancers detected by conventional means. The MCED test was likely to find clinically significant cancers without contributing to overdiagnosis.
PMID:41818645 | DOI:10.1200/PO-25-00725
