# Integrating Circulating Tumor DNA (ctDNA) Into Postoperative Surveillance After the Resection of Intrahepatic Cholangiocarcinoma: A Proposed Hybrid Imaging-Molecular Framework

## TL;DR

This paper proposes a new surveillance strategy for intrahepatic cholangiocarcinoma that combines imaging with ctDNA to detect early recurrence.

## Contribution

A hybrid imaging-molecular framework is proposed for postoperative surveillance of ICC, emphasizing ctDNA as a complementary tool.

## Key findings

- ctDNA can detect tumor recurrence 2-6 months earlier than imaging in solid tumors.
- Current ICC-specific performance metrics for ctDNA are limited and require further validation.
- ctDNA should be used alongside imaging, not as a standalone method, due to practical challenges.

## Abstract

Recurrence after curative-intent resection remains common in intrahepatic cholangiocarcinoma (ICC) and continues to limit long-term survival. Although repeat liver resection may benefit carefully selected patients, this opportunity is often lost because recurrence is detected only after radiographic progression. Postoperative surveillance relies primarily on cross-sectional imaging, which performs well for macroscopic disease but lacks sensitivity for microscopic residual tumor. Consequently, relapse is frequently recognized only after structural visibility, when tumor biology may already be unfavorable. Minimal residual disease (MRD) represents the persistence of viable malignant cells below the threshold of radiographic detection and is increasingly implicated in early relapse. Circulating tumor DNA (ctDNA) analysis enables the detection of tumor-specific genomic alterations in peripheral blood and reflects active tumor biology rather than delayed anatomical change. Across solid tumors, ctDNA positivity has been associated with recurrence lead times of approximately 2-6 months before radiographic detection; however, ICC-specific prospective performance metrics, including sensitivity, specificity, and predictive values, remain limited and incompletely defined. Important practical challenges include assay variability, tumor shedding heterogeneity in biliary tract cancers, clonal hematopoiesis-related false positives, and uncertainty in managing isolated low-level molecular positivity. Accordingly, ctDNA should be considered a complementary rather than a replacement modality. This narrative review synthesizes current imaging and molecular evidence and proposes a hypothesis-generating hybrid imaging-molecular surveillance framework intended to guide future prospective validation rather than serve as an evidence-validated clinical algorithm.