Treatment patterns and survival outcomes in Klatskin tumors: A real-world analysis of the TriNetX network.

513 Background: Klatskin tumors (perihilar cholangiocarcinoma) are rare biliary tract malignancies with poor prognosis. Surgical resection offers the only chance of long-term survival, but most patients present with unresectable disease. Systemic options now include gemcitabine-cisplatin, recently combined with the PD-L1 inhibitor durvalumab as standard first-line therapy, and FOLFOX in the second-line setting. Real-world outcomes with immunotherapy and disparities in treatment delivery remain underexplored. Methods: We conducted a retrospective cohort study using the TriNetX Research Network (2010–2024). Adult patients (≥18 years) with perihilar cholangiocarcinoma were identified using ICD-10-CM codes. Patients were stratified into four groups: (1) surgical resection, (2) gemcitabine/cisplatin, (3) gemcitabine/cisplatin + durvalumab, and (4) best supportive care. Primary outcome was overall survival (OS). Secondary outcomes included 12- and 24-month survival and treatment disparities by age, sex, race/ethnicity, and insurance. Kaplan–Meier and multivariable Cox regression were used for analysis. Results: Among 2,146 patients, 21% underwent surgical resection, 32% received gemcitabine/cisplatin, 16% received gemcitabine/cisplatin + durvalumab, and 31% received supportive care. Median OS was 26.4 months with resection, 11.2 months with gemcitabine/cisplatin, 14.8 months with gemcitabine/cisplatin + durvalumab, and 4.7 months with supportive care (p<0.001). Two-year survival was 42% with resection, 25% with chemo-immunotherapy, 18% with chemotherapy alone, and 6% with supportive care. On multivariable analysis, both resection (HR 0.38, 95% CI 0.32–0.46, p<0.001) and chemo-immunotherapy (HR 0.71, 95% CI 0.59–0.85, p<0.01) were independently associated with improved OS compared to supportive care. Black patients and those with Medicaid/uninsured status were significantly less likely to undergo resection (OR 0.58 and OR 0.64, respectively, p<0.01). Women were also underrepresented in surgical cohorts compared with men (18% vs. 23%, p=0.04). Conclusions: In this large real-world cohort, surgical resection remained the most effective strategy for Klatskin tumors, but chemo-immunotherapy with gemcitabine/cisplatin + durvalumab provided meaningful survival benefit over chemotherapy alone. Despite advances, fewer than one-quarter of patients underwent resection, and disparities persisted in access to both surgery and systemic therapies.