Prognostic Significance of Blood-Based Multicancer Detection in Circulating Tumor DNA: Five-Year Outcomes Analysis
Charles Swanton1, Alan Bryce2, Allen L Cohn3
1Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, United Kingdom.
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.
