A groundbreaking study has demonstrated that circulating tumor DNA (ctDNA) testing can serve as a powerful prognostic biomarker for predicting relapse in patients with early-stage biliary tract cancer (BTC) who have undergone curative resection.
The findings, published in JCO Precision Oncology, represent the first evaluation of ctDNA's prognostic value in resected BTC in a real-world setting, according to lead study author Dr. James Yu, a radiation oncologist at Smilow Cancer Hospital at Saint Francis Hospital in Hartford, Connecticut.
"Our findings demonstrate that ctDNA detected by this personalized, tumor-informed assay is highly prognostic of relapse-free survival and that ctDNA monitoring has the potential to detect molecular recurrence early ahead of standard radiographic surveillance in early-stage BTC," Yu and colleagues wrote.
Study Design and Patient Characteristics
The retrospective, multicenter cohort study analyzed 195 plasma samples collected from 56 patients with biliary tract cancer who had undergone curative resection. The cohort included 61% males and 39% females, with a median follow-up of 12.8 months.
Researchers assessed ctDNA positivity and negativity during both the molecular residual disease window and the surveillance period. The study utilized a personalized, tumor-informed ctDNA assay to detect minimal residual disease (MRD) following surgery.
Significant Findings on Recurrence Detection
After a median follow-up of 12.8 months from surgery, the results were striking. Patients who tested ctDNA-positive during the molecular residual disease window had a median relapse-free survival of just 6.6 months, while those who tested negative had not yet reached median relapse-free survival.
Among the 16 patients who experienced confirmed recurrence, ctDNA identified the recurrence in 93.8% (15 of 16) of cases, with an average lead time of 3.7 months compared to standard imaging techniques. This early detection capability could potentially provide a critical window for intervention before clinical recurrence becomes apparent.
Notably, carbohydrate antigen 19-9 levels, which are commonly used as tumor markers, did not show a significant correlation with relapse-free survival, highlighting the superior prognostic value of ctDNA testing in this patient population.
Implications for Clinical Practice
Biliary tract cancer is a rare but aggressive malignancy with limited treatment options. The current standard of care for early-stage BTC involves surgical resection followed by adjuvant capecitabine with or without chemoradiation.
The study findings suggest that ctDNA testing could play a valuable role in post-surgical surveillance and treatment decision-making. In particular, the researchers noted that 10.8% (4 of 37) of non-recurrent patients with ctDNA-negative results initially had positive imaging findings that were not confirmed by subsequent testing.
"This highlights ctDNA testing's potential to determine which indeterminate radiographic findings warrant further imaging or invasive biopsy," the authors explained, suggesting that the technology could help reduce unnecessary procedures while ensuring that true recurrences are detected promptly.
Growing Evidence for ctDNA Across Cancer Types
The findings align with emerging research on ctDNA's utility in other cancer types. In colorectal cancer, for example, recent data from the VICTORI study presented at the American Association for Cancer Research Annual Meeting 2025 showed that a novel ctDNA-based liquid biopsy assay could identify recurrence indicators before imaging.
In that study, researchers found that ctDNA detection as early as two weeks after surgery was associated with reduced disease-free survival, with the strongest association observed at week 8 post-surgery.
Future Directions
While the results from the biliary tract cancer study are promising, the authors acknowledge that further research is needed to confirm their findings and determine whether early detection of recurrence via ctDNA monitoring can ultimately translate into survival benefits.
"Further larger randomized controlled trials are warranted to confirm these findings," the study authors concluded. "Whether this early detection of recurrence by ctDNA can ultimately be translated into survival benefits by early intervention is the next question of investigation."
As liquid biopsy technologies continue to advance, ctDNA testing may become an increasingly important tool in the management of biliary tract cancer and other malignancies, potentially allowing for more personalized and timely interventions to improve patient outcomes.
