Tumor-Informed ctDNA Surveillance for HCC and CCA After Liver Transplant Shows High Specificity
Key Clinical Summary
- Personalized, tumor-informed circulating tumor DNA (ctDNA) assays were feasible for post–liver transplant surveillance in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA).
- Among evaluable patients, ctDNA demonstrated 75% sensitivity and 100% specificity for detecting recurrence, comparable to standard tumor biomarkers.
- High assay failure rates due to insufficient tumor tissue and compliance challenges may limit routine surveillance use, supporting a potential confirmatory role.
Recurrence after liver transplantation (LT) for primary liver cancers remains uncommon but carries a poor prognosis when it occurs. Earlier detection could improve outcomes. A recent study evaluated whether personalized, tumor-informed ctDNA assays from peripheral blood could support post-LT surveillance in patients with HCC or CCA, alongside standard imaging and tumor biomarkers.
Study Findings
The study included 38 LT recipients with HCC or CCA undergoing longitudinal surveillance using personalized ctDNA assays in addition to standard-of-care imaging and peripheral tumor biomarkers, including alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9). Testing frequency was approximately every 4 months, aligning with recommended surveillance intervals of 3 to 6 months.
Radiologic recurrence was identified in 6 patients. Of these, ctDNA assays were positive in 3 patients and negative or insufficient to process (ITP) in the remaining three. Overall, 9 ctDNA assays were deemed ITP, primarily due to insufficient primary tumor tissue for assay development.
Among the 31 patients with evaluable ctDNA results, the assay demonstrated a sensitivity of 75% (95% CI, 19%-99%) and a specificity of 100% (95% CI, 87%-100%). In comparison, standard tumor biomarkers showed the same sensitivity of 75% (95% CI, 19%-99%) but a lower specificity of 93% (95% CI, 76%-99%). Statistical comparisons between ctDNA and biomarkers were not significant.
Notably, ctDNA positivity preceded imaging-based diagnosis in only one patient, indicating limited lead-time advantage in this cohort.
Clinical Implications
For oncologists and transplant teams, these findings suggest that tumor-informed ctDNA assays are technically feasible in the post-LT setting and offer excellent specificity for recurrence detection. High specificity is particularly relevant in transplant recipients, where invasive diagnostic procedures such as biopsy carry added risk.
However, the relatively low sensitivity and high ITP rate raise concerns about ctDNA as a standalone surveillance tool. The failure rate appears linked to the effectiveness of pre-transplant locoregional therapies, which may reduce available tumor tissue for assay design. Additionally, increasing delays between test ordering and blood collection highlight potential compliance challenges during the recommended 5-year surveillance period.
For oncology payers and pathway developers, these results suggest ctDNA may be best positioned as a confirmatory or diagnostic adjunct rather than a replacement for imaging. Its potential role may be to reduce unnecessary biopsies when conventional imaging or biomarkers raise suspicion for recurrence.
The study authors concluded that “ctDNA assays show promise in confirming recurrence and minimizing the need for invasive biopsy,” while emphasizing that “additional prospective studies are needed to confirm ctDNA test utility in surveillance protocols.” They noted that the high specificity and lower sensitivity support a diagnostic rather than screening role in post-LT surveillance for primary liver cancers.
Conclusion
Personalized tumor-informed ctDNA testing after liver transplantation for HCC or CCA is feasible and highly specific but limited by sensitivity, assay failure, and compliance issues. Larger prospective studies are needed to define how ctDNA can be optimally integrated into post-transplant surveillance pathways before routine clinical adoption.
Reference
Abdelrahim M, Connor AA, Esmail A, et al. Tumor-informed circulating tumor DNA assay for surveillance post-liver transplantation in patients with hepatocellular and cholangiocarcinoma. J Gastrointest Oncol. 2025;16(4):1573-1585. doi:10.21037/jgo-24-791
