Gemcitabine-cisplatin induction treatment in patients with locally advanced perihilar cholangiocarcinoma (IMPACCA): A prospective registration study

Background: Induction treatment may be beneficial in patients with unresectable locally advanced perihilar cholangiocarcinoma (LAPCCA). Prospective studies are currently lacking. This study aimed to assess the feasibility and efficacy of gemcitabine and cisplatin as induction treatment in patients with unresectable LAPCCA.

Methods: In this prospective single-center registration study, consecutive patients with unresectable LAPCCA who received induction treatment with gemcitabine and cisplatin in an intent to downsize the tumor to allow for resection were included. The primary outcomes were resection rate and overall survival.

Results: Overall, 265 patients with perihilar cholangiocarcinoma were screened between January 2020 and June 2023, of whom 23 patients (9%) with unresectable LAPCCA met the eligibility criteria. Eight patients (35%) became eligible for resection, of whom six ultimately underwent resection (resection rate, 26% (11-42%)). Two out of 23 patients (9%) experienced adverse events grade≥3, forcing one to stop induction treatment. Compared to baseline, CA19.9 levels decreased by 42% (95 % CI, -65 to -5%; P = 0.039) and 8% (-44 to 112%; P = 0.80) at the first and second restaging, respectively. Tumor size did not significantly decrease after chemotherapy. Median overall survival was 27 months (18-36), with 40 (24-56) in the resected and 19 (13-26) in the unresected group (P = 0.127).

Conclusion: Patients with LAPCCA frequently tolerate induction gemcitabine-cisplatin, leading to a 26% resection rate with 40 months overall survival. These findings support routine re-staging after three to six cycles of palliative treatment, and lay the groundwork for future prospective trials in this patient group.