Multi-cancer early detection (MCED) test performance in cancer survivors.

Abstract

1628 Background: Cancer survivors (CS) are at risk for recurrent or new primary tumors in any organ, but there is lack of clear guidance and options for long-term surveillance. We analyzed the performance of a blood-based MCED test that detects cancer-specific methylation patterns and predicts cancer signal origin (CSO) in CS in the PATHFINDER study (PF; NCT04241796). Methods: PF enrolled6662 participants (pts) ≥50 yr without clinical suspicion of cancer; 6578 samples were analyzed with a refined MCED test. Pts were stratified by CS status (treated cancer >3 yr prior to study vs no prior cancer); in CS, prior cancer type and time from diagnosis were recorded. Cancers diagnosed during PF were classified as recurrent or new primaries. Positive predictive value (PPV), number needed to screen (NNTS), and CSO accuracy were assessed. Results: CS comprised 25% (1609/6578) of pts analyzed; 73% were female. Median age was 66 yr; age at prior diagnosis was 8% <40, 22% 40-49, 70% ≥50 yr. Most common prior cancers were breast (749, 47%), melanoma (163, 10%) and prostate (141, 9%). A higher proportion of pts with cancer diagnosis was observed in CS vs those with no prior cancer (Table). Among 20 CS with cancer signal detected, 10 cancers were diagnosed in 9 pts; 5 recurrent (all metastatic breast) and 5 new primaries (uterine stage 1 [found as incidental lesion on imaging during MCED-triggered workup for recurrent breast cancer], sarcoma stage 2, ovarian stage 3, lymphoma and CRC stage 4). During 1-yr follow-up in those with negative MCED result, new cancer diagnoses in CS included 13 recurrences (all local) and 15 new primaries. Of the 13 new primaries with known stage, 46% were stage 1 (2 breast, 1 melanoma, 1 thyroid, 1 lymphoma, 1 lung), 31% stage 2 (2 lymphomas, 1 melanoma, 1 breast), 15% stage 3 (1 pancreas, 1 pleural mesothelioma), and 7% stage 4 (1 prostate). Yield, PPV, NNTS, and CSO accuracy were similar in CS and no prior cancer group. Years between MCED cancer detection and prior cancer in CS was 4-11 for recurrent and 8-15 for new primaries. Most (4/5) new primaries were cancers with no USPSTF-recommended screenings. Conclusions: The MCED test detected both cancer recurrences and new primaries in CS for whom multiple years had elapsed since their original diagnosis, potentially expanding surveillance options for this patient group. Cancers in CS not detected by MCED were predominantly early stage. Test performance was similar in those with and without a cancer history. Clinical trial information: NCT04241796 . [Table: see text]