Approximately 10-25% of cancer patients (pts) develop MPCs, often metachronous, resulting from environmental exposures, prior therapies, and inherited genetic factors. Monitoring individual tumor progression is challenging due to the lack of sensitive biomarkers and tumor-specific imaging characteristics that can distinguish between recurrences and MPCs. This study demonstrates the feasibility of individually monitoring MPCs using a tumor-informed ctDNA assay.

This retrospective analysis used real-world data from commercial ctDNA testing in pts with MPCs who had a personalized, tumor-informed, mPCR-NGS ctDNA assay (SignateraTM, Natera, Inc.) designed for each primary tumor. Pt treatment and the collection of longitudinal blood samples were at the treating physician's discretion. Clinicopathologic information for ctDNA analyses was collected retrospectively from Natera’s commercial database. The patterns of tumor-specific ctDNA results for each pt were summarized.

In total, 41 pts with MPCs underwent ctDNA monitoring for two (40 pts) or three (1 pt) primary tumors. Tumor A included breast (21.9%, n=9), gastrointestinal (GI) (31.7%, n=13), genitourinary (GU) (14.6%, n=6), gynecologic (gyn) (4.9%, n=2), skin (14.6%, n=6), sarcoma (2.4%, n=1), lung cancer (7.3%, n=3), and unknown histology (2.4%, n=1). Stage distribution for Tumor A was: stage I: 5 (12.2%), stage II: 8 (19.5%), stage III: 20 (48.8%), stage IV: 6 (14.6%), and unknown: 2 (4.9%). Tumors B and C comprised of GI (38.6%, n=17), gyn (20.5%, n=9), breast (13.6%, n=6), skin (13.6%, n=6), GU (4.5%, n=2), lung (4.5%, n=2), hematological cancer (2.3%, n=1), and unknown histology (2.3%, n=1). Stage distribution for Tumor B was: stage I: 8 (18.2%), stage II: 5 (11.4%), stage III: 16 (36.4%), stage IV: 10 (22.7%), and unknown: 5 (11.4%). Among these, 17 pts had multiple primary tumors originating in the same organ. Analysis of clinical data was performed for 33 pts, including one with three primary tumors. The median follow-up was 14.5 months for Tumor A and 2.7 months for Tumor B/C. A total of 302 ctDNA tests were performed: 241 for Tumor A and 61 for Tumor B. Among 33 pts, one tested ctDNA negative in both tumors, while 4 pts tested positive for both tumors at some point. 12 pts tested positive for Tumor A but were consistently negative for tumor B. Lastly, 16 pts were positive for Tumor B or C but serially negative for Tumor A.

This study demonstrates the feasibility of real-time tracking of MPCs using tumor-informed ctDNA assays. Reliable assessment of tumor-specific molecular disease burden during surveillance and treatment monitoring can be critical for timely and informed clinical management decisions and personalized treatment plans.