Combining Selective Internal Radiation Therapy (SIRT) and Systemic Therapy in Intrahepatic Cholangiocarcinoma

Background: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer, with increasing presentation. Less than one-third of patients are resectable at diagnosis, and the first-line systemic standard, gemcitabine–cisplatin plus durvalumab, yields a modest median overall survival (OS) of approximately 13 months. In liver-dominant iCCA, selective internal radiation therapy (SIRT) with yttrium-90 (90Y) microspheres can deliver a high, parenchyma-sparing tumoricidal dose in loco and, paired with systemic therapy, is a valid treatment option. Methods: This commentary evaluates the retrospective and prospective data, comparative cohorts, registries, and meta-analyses of SIRT with systemic therapy in unresectable iCCA. Results: Across the data sets identified, the efficacy signal is in favor of combined approaches when SIRT is delivered in the first line selectively and concurrently with chemotherapy, reaching a median OS of about 22 months with 98% disease control. Propensity-weighted comparisons describe the added value of SIRT in improving OS and roughly doubling the progression-free survival and secondary resection rate. Downstaging to surgery (in approximately 5–19%) and, in highly selected patients with liver predominant disease, transplants can yield favorable longer-term survival with a good safety profile. Conclusions: To date, no completed randomized trial exists on combined locoregional SIRT and systemic therapy in patients with iCCA. SIRT should be considered a multimodal personalized therapeutic treatment option in patients with upfront unresecatable liver predominant disease.