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

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.

This commentary evaluates the retrospective and prospective data, comparative cohorts, registries, and meta-analyses of SIRT with systemic therapy in unresectable iCCA.

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.

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.