At the 2025 Annual Cholangiocarcinoma Foundation Conference, a working group that included co-chairs Simon Rushbrook and Bruno Odisio, as well as Alejandro Forner, Ana Lleo, Iwan Paolucci, Mike Goggins, Irene Bargellini, Jean-Charles Nault, Shahid Khan, Terence Gade, Vincenzo Cardinale, Angela Ammirabile, Leigh Nash, and Leslie Swanson, presented on radiomics, biomarkers, and optimal biliary decompression.
Cholangiocarcinoma (CCA), a rare but aggressive malignancy of the bile ducts, has long presented significant diagnostic and treatment challenges. Recent advancements in radiomics, biomarkers, and optimal biliary decompression have provided new opportunities to improve outcomes for patients. These innovations are reshaping the understanding and management of this complex disease, offering noninvasive diagnostic tools, enhanced prognostic capabilities, and improved therapeutic strategies.
Radiomics is emerging as a powerful tool in the diagnosis and management of CCA. By extracting and analyzing quantitative features from medical imaging modalities such as CT, MRI, and PET-CT, radiomics allows clinicians to uncover tumor characteristics that are invisible to the naked eye. These features are related to tumor size, shape, intensity, and texture and can be transformed into data for statistical analysis, enabling the creation of diagnostic and prognostic models. One of the significant advantages of radiomics lies in its ability to assess tumor heterogeneity, a critical factor in CCA prognosis. Heterogeneous tumors are often associated with poorer outcomes, and radiomics provides a noninvasive method to evaluate the heterogeneity of tumors comprehensively. For example, radiomics has been successfully applied to identify tumor subtypes, detect microvascular and neural invasion, and assess lymph node status, all of which are crucial factors in determining treatment strategies. However, challenges remain. The accuracy of current radiomics models, typically approximately 80%, falls short of the near-perfect sensitivity required for widespread clinical adoption. Additionally, the lack of external validation studies and standardization across imaging techniques limits reproducibility and reliability. Future research must address these gaps, focusing on integrating radiomics with clinical data to enhance its diagnostic and prognostic utility.
Biomarkers also hold significant promise for early detection and personalized treatment of CCA. Circulating tumor DNA (ctDNA) has shown potential in diagnosing CCA and monitoring disease progression. Innovations in next-generation sequencing have enabled the detection of DNA mutations, methylation patterns, and chromosomal rearrangements, providing valuable insights into tumor biology. For instance, ctDNA has demonstrated prognostic value, often reflecting the presence of micrometastases. However, its diagnostic utility remains limited due to low signal sensitivity, particularly in early-stage cancers. To overcome this limitation, researchers are exploring advanced methods to analyze DNA fragmentation and aneuploidy, which could enhance the specificity and sensitivity of blood-based diagnostics. Additionally, traditional protein biomarkers like CA-99, although widely used, exhibit significant individual variability that limits their reliability. Personalizing biomarker monitoring by considering genetic factors and longitudinal trends could unlock their full potential, particularly for patients under surveillance for primary sclerosing cholangitis, a known risk factor for CCA. Beyond blood-based biomarkers, novel approaches to analyzing bile and tissue samples are gaining traction. Techniques such as branched DNA-enhanced RNA in situ hybridization and next-generation sequencing applied to bile or biopsy samples offer new avenues for improving diagnostic accuracy and identifying actionable genetic alterations.
Biliary decompression is a critical intervention for patients with biliary obstruction due to CCA. It aims to alleviate jaundice, reduce complications, and improve eligibility for treatments like surgery or chemotherapy. However, determining the optimal approach to biliary decompression, whether endoscopic or percutaneous, remains a topic of ongoing debate. Recent studies have highlighted the benefits of percutaneous biliary drainage (PBD) in reducing the risk of hepatic failure in patients with high bilirubin levels. However, this approach carries risks including infection and bleeding, necessitating careful patient selection. Noninvasive tools such as magnetic resonance elastography measure liver stiffness and jaundice severity and may help identify patients most likely to benefit from PBD. For unresectable disease, innovative techniques like primary percutaneous stenting, which avoids crossing the ampulla and minimizes infection risk, are showing promise. Early results from clinical trials indicate lower complication rates and improved survival outcomes for primary percutaneous stenting compared with traditional approaches. These advancements underscore the importance of tailoring biliary decompression strategies to individual patient needs and disease characteristics. The convergence of radiomics, biomarkers, and optimized biliary decompression represents a significant step forward in the fight against CCA.
Radiomics offers a noninvasive window into tumor biology, whereas biomarkers may enable personalized treatment strategies, and refined biliary decompression techniques improve patient outcomes. Despite these advancements, challenges remain. Standardization, external validation, and integration across these modalities are essential to translate these innovations into routine clinical practice. Furthermore, there are gaps in biomarker research, including the need for multiple biomarkers and risk-prediction markers in high-risk conditions. Future research should focus on combining these tools into comprehensive diagnostic and therapeutic pathways, ensuring that patients with CCA receive the most effective and personalized care possible. With continued investment in multidisciplinary approaches and cutting-edge technologies, the outlook for patients with CCA is brighter than ever, paving the way for improved survival and quality of life in this challenging disease.
Rushbrook S, Odisio B. WG1-Diagnostics/Interventional. Presented at: 2025 Annual Cholangiocarcinoma Foundation Conference. April 9-11, 2025; Salt Lake City, UT.
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