The 2025 Annual Cholangiocarcinoma (CCA) Summit brought together experts to discuss innovative strategies to improve surgical outcomes in CCA. A unifying theme across the session was the integration of systemic therapies, radiotherapy, and advanced surgical techniques to achieve complete resections and enhance survival outcomes in patients with high-risk CCA, where surgery remains the only curative option.
Laleh Melstrom, MD, began the discussion by outlining the evolving strategies for converting unresectable or borderline-resectable intrahepatic CCA (iCCA) to resectable disease. She highlighted the complexities of high-risk resectable cases, which are often marked by vascular invasion, multifocality, lymph node metastases, and elevated CA 19-9 levels. These factors are often a sign of a worse prognosis, making multimodality therapeutic approaches essential.
To guide surgical decision-making, Dr Melstrom emphasized the utility of prognostic tools and biomarkers. She cited a study of 367 patients with iCCA, in which a prognostic nomogram demonstrated superior predictive accuracy for survival outcomes compared with the American Joint Committee on Cancer staging system, with a concordance index of 0.74.1 Additionally, she described a newly developed digital application, based on a multicenter study, which predicts 90-day mortality and overall survival (OS) using clinical factors such as tumor size, the use of neoadjuvant therapy, and CA 19-9 levels.1
Dr Melstrom then reviewed several tumor downstaging strategies that aim to shrink tumors and enable surgical resection. She highlighted systemic therapy, radioembolization, and immunotherapy as promising approaches. For example, the ABC trial showed that gemcitabine/cisplatin improved OS (11.7 vs 8.6 months) and tumor control rates (81.4% vs 71.8%) compared with gemcitabine alone in patients with locally advanced or metastatic biliary tract cancer (BTC).1 Similarly, the TOPAZ-1 study revealed that the addition of durvalumab to gemcitabine/cisplatin significantly increased objective response rates compared with gemcitabine/cisplatin alone (26.7% vs 18.7%, respectively).1
Real-world data also support downstaging strategies in iCCA. Neoadjuvant regimens have shown strong potential in allowing patients to proceed to surgery. As an example, Dr Melstrom shared the results from the phase 2 NEO-GAP study in high-risk iCCA, where 73% of patients completed neoadjuvant gemcitabine, cisplatin, and nab-paclitaxel treatment, and proceeded to surgery.1 Dr Melstrom noted that molecular profiling is increasingly guiding treatment decisions for CCA. Specifically, she highlighted that ARID1A mutations have been associated with reduced progression-free survival (PFS) outcomes in patients receiving gemcitabine/cisplatin, highlighting the need for personalized approaches for selecting effective therapies. Dr Melstrom further highlighted ongoing clinical trials, such as PURITY, NEO-GAP, and ZSAB-TransGOLP, which are actively advancing neoadjuvant and conversion strategies for BTC.
Next, Ryan Fields, MD, reviewed adjuvant therapies in CCA, emphasizing that the impact of adjuvant therapies on survival benefits may vary based on patient and disease factors.2 Dr Fields discussed key adjuvant therapy trials in BTC, including BILCAP, STAMP, and PRODIGE 12-ACCORD 18, highlighting mixed or modest results in improving survival outcomes. In consideration of these limited gains, Dr Fields suggested exploring alternative strategies, such as neoadjuvant approaches and “sandwich” approaches, which combine preoperative and postoperative treatments to maximize disease control.
To illustrate how neoadjuvant strategies can improve outcomes, Dr Fields referenced the SWOG S1801 melanoma trial, where 3 preoperative doses of programmed death-ligand 1 inhibitors followed by 15 cycles of adjuvant therapy significantly improved PFS compared with 18 cycles of adjuvant therapy (79% vs 30%).2 Dr Fields also discussed a study where chemoradiation and immunotherapy in the adjuvant setting improved survival outcomes in patients with extrahepatic CCA and gallbladder cancer. Specifically, patients who received immunotherapy (camrelizumab) in combination with capecitabine and radiotherapy showed a 3-year OS rate of 58.2% compared with 30.5% for patients under observation alone.2
Additionally, Dr Fields highlighted the prognostic value of biomarkers, such as the systemic immune-inflammation index and CA 19-9, which could stratify patients and guide therapeutic decisions in the adjuvant settings. Dr Fields concluded that innovative trial designs and further research are essential to advancing the role of adjuvant therapies in BTC.
During the discussion, experts reviewed recent trials and strategies for BTCs, raising concerns about high postoperative mortality rates and challenges with preoperative radiation. Barriers to transplantation, particularly insurance limitations, were also highlighted, with calls for greater collaboration across smaller trials. Recommendations emphasized regular multidisciplinary reviews, clear treatment goals, and tailoring interventions to tumor biology and location. The session stressed the importance of accurate prognostic tools, biomarker-driven approaches, and strong collaboration to improve BTC patient outcomes.
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