The Evolving Role of Neoadjuvant Radiation Therapy in Cholangiocarcinoma
Shifting radiation therapy into the neoadjuvant setting for borderline resectable or locally advanced cholangiocarcinoma offers potential clinical advantages in margin-negative resections, according to insights shared ahead of the 2026 Chicago Cholangiocarcinoma Symposium. Ethan B. Ludmir, MD, associate professor in the Department of Gastrointestinal Radiation Oncology at The University of Texas MD Anderson Cancer Center, detailed evolving therapeutic options during a discussion with CancerNetwork regarding preoperative and nonoperative care paradigms.
- Neoadjuvant radiation is being evaluated to improve the likelihood of R0 surgical resections in select extrahepatic cholangiocarcinoma cases, drawing on parallels from pancreatic cancer management.
- Modern delivery techniques, including hypofractionation, stereotactic body radiation therapy (SBRT), and proton beam therapy, are being discussed in the context of preoperative and nonoperative care.
- Sequencing radiation alongside chemoimmunotherapy regimens—such as gemcitabine, cisplatin, and durvalumab—alongside recent drug approvals like lirafugratinib (Lyrfigtu) for FGFR2-altered tumors, highlights a rapidly evolving multidisciplinary approach.
The Clinical Rationale for Preoperative Radiation
Most existing clinical data regarding radiotherapy in cholangiocarcinoma stem from the adjuvant setting, notably trials like the SWOG S0809 study (NCT00789958). These historical protocols frequently utilized radiation as a postoperative cleanup strategy for margin-positive resections or patients presenting with adverse pathologic features such as T2-stage disease or higher or pathologic node positivity. However, patient tolerance often presents a challenge in the adjuvant phase following major hepatobiliary resections.
According to Ludmir, clinicians increasingly extrapolate from sister diseases such as pancreatic cancer when evaluating distal extrahepatic cholangiocarcinoma, given the anatomical overlap in the head of the pancreas. Evidence from borderline resectable pancreatic cancer suggests that preoperative radiation is generally better tolerated by patients and can assist surgeons in achieving an R0 resection by clearing disease away from vital vasculature. Individual practitioner expertise remains a critical variable, as well-timed radiation delivered six to eight weeks prior to surgery can foster edematous tissue planes that facilitate tumor removal.
Anatomical Subsets and Tumor Location Considerations
Patient selection for neoadjuvant radiation depends heavily on whether the tumor is intrahepatic or extrahepatic. Intrahepatic cholangiocarcinoma currently lacks strong prospective evidence supporting neoadjuvant or adjuvant radiation paradigms, with population studies like those derived from the National Cancer Database offering limited guidance. For resectable intrahepatic disease, perioperative chemotherapy and chemoimmunotherapy remain the primary focus of evolving clinical trials.
Despite the paucity of broad population data, multidisciplinary teams at tertiary and quaternary care centers may occasionally incorporate radiation for select intrahepatic cases involving tumors abutting major hepatic vessels to secure clear surgical margins during hepatectomy. Conversely, distal extrahepatic cholangiocarcinoma represents an anatomical setting where preoperative radiation aligns closely with established pancreatic cancer treatment models. Hilar cholangiocarcinoma tumors occupy a more complex clinical space where therapeutic strategies remain highly individualized.
Integrating Multimodal Regimen Sequencing
Modern clinical investigation in cholangiocarcinoma increasingly focuses on sequencing radiation alongside systemic therapies, including chemoimmunotherapy combinations comprising gemcitabine, cisplatin, and durvalumab. Targeted therapeutic advancements—exemplified by the September 23, 2026, FDA approval of lirafugratinib (Lyrfigtu) for patients with FGFR2-altered cholangiocarcinoma—continue to refine how oncologists sequence local-regional treatments with systemic and targeted agents. Clinical endpoints such as overall survival remain central to evaluating these emerging strategies in trials like the randomized phase 2 HYPERION CCA study (NCT06858735).
Patients diagnosed with biliary tract malignancies should consult with qualified hepatobiliary oncologists and radiation oncology specialists to explore multidisciplinary evaluation pathways and ongoing clinical trial opportunities.
*Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider regarding any medical condition, diagnosis, or treatment plan.*