45Prognostic Utility of ctDNA vs. Conventional Biomarkers in Resected Biliary Tract Cancer: A Real-World Analysis
Maen Abdelrahim, Abdullah Esmai1, Antony Tin, Lokesh Bathla, Catherine Bridges, Chris M Brewer, Jenifer Ferguson, James Yu, Aiwu Ruth He, Timothy Cannon, Arthur Winer, Gentry King, Amit Mahipal, Arun Nagarajan, Joseph Franses, Midhun Malla, Michael M Khayat, Adham Jurdi, Minetta C Liu, Richard KimAbstract
Background
Biliary tract cancer (BTC) remains a rare but aggressive malignancy of the gastrointestinal system. Although surgical resection offers the only potential for a cure in early-stage disease, the clinical outlook is often marred by high recurrence rates, typically ranging between 60% and 70%. These high rates of relapse contribute significantly to the poor prognosis associated with the disease. While traditional blood-based biomarkers have long been utilized for monitoring, circulating tumor DNA (ctDNA) has recently emerged as a potentially more reliable prognostic tool. This study sought to evaluate the prognostic utility of ctDNA in comparison to conventional biomarkers within a real-world patient cohort.
Methods
This study involved a retrospective analysis of real-world data from 167 patients diagnosed with stage 1-111 resectable BTC between July 2020 and February 2024. Patients underwent ctDNA analysis using a personalized, tumor-informed 16-plex mPCR-NGS assay (Signatera™). A total of 769 plasma samples were collected and analyzed across three critical timeframes: prior to surgery, within a 2-12-week post-operative molecular residual disease (MRD) window, and longitudinally throughout a surveillance window until death or the final follow-up. The prognostic performance of ctDNA was directly compared against traditional markers, specifically Carbohydrate Antigen 19-9 (CA19-9) and Carcinoembryonic Antigen (CEA).
Results
The patient cohort had a median age of 68 years and a median follow-up period of 21 months. Analysis revealed ctDNA-positivity in 23% of patients during the MRD window and 32% during the surveillance period. Detection of ctDNA at either stage was significantly correlated with inferior relapse-free survival (RFS) and overall survival (OS). Multivariate analysis further identified ctDNA-positivity during surveillance as the most robust prognostic factor for RFS, yielding a hazard ratio of 8.17, 95% Cl: 2.98-22.4, P < 0.001. In striking contrast, CA 19-9 and CEA levels failed to provide significant predictive value for either RFS or OS during the MRD or surveillance windows.
Conclusions
These findings demonstrate that post-surgical ctDNA detection using a tumor-informed assay provides significant prognostic value in both the immediate MRD window and long-term surveillance. Given its clear superiority over traditional biomarkers like CA 19-9 and CEA, ctDNA appears to be a more effective tool for post-operative risk stratification. Integrating ctDNA analysis into the clinical management of BTC could enhance decision-making and lead to more personalized treatment strategies for patients at high risk of recurrence.