Real-World Evidence from a Nationwide Prospective Study of the Efficacy/Safety of Systemic Therapy for Unresectable Hepatocellular Carcinoma: First 1,000 Patients of the PRISM Study.

Background: The PRISM study is a nationwide, multicenter, prospective observational study in Japan evaluating the real-world efficacy and safety of systemic therapies for unresectable hepatocellular carcinoma (HCC). HCC patients starting systemic therapy are prospectively enrolled, enabling assessment of outcomes and tolerability across treatment lines. By capturing all patients treated in routine practice, the study is expected to provide a clear picture of the actual treatment outcomes in Japan. Methods: We analyzed the first 1,000 patients enrolled between July 2020 and July 2022, focusing on outcomes of first-line therapy and subsequent patterns. Data on demographics, tumor stage, liver function, regimens, survival, and adverse events (AEs) were prospectively collected and centrally monitored. Survival was estimated by Kaplan-Meier method, and tumor responses were assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST). Results: Of 935 evaluable patients, 82.8% received atezolizumab + bevacizumab (Atezo+Bev) and 15.2% lenvatinib as first-line therapy. Median overall survival and progression-free survival were 21.8 and 7.7 months for Atezo+Bev, respectively, and 20.8 and 6.7 months for lenvatinib, with overall survival numerically longer than that reported in pivotal clinical trials, while progression-free survival remained comparable. Objective response rates were 29.6% (RECIST) and 35.0% (mRECIST) for Atezo+Bev, 24.6% and 35.2% for lenvatinib, and 0% and 6.3% for sorafenib by RECIST and mRECIST, respectively. Grade ≥3 treatment-related AEs occurred in 21.6% and 22.9%, with safety profiles consistent with prior reports. Approximately 50% of patients received second-line therapy, most often lenvatinib after Atezo+Bev and vice versa, with a median progression-free survival of ∼4 months; later-line regimens yielded even shorter benefit. Conclusion: The PRISM study confirms the real-world reproducibility of Atezo+Bev and lenvatinib in Japan, demonstrating their feasibility across diverse patient populations. Ongoing follow-up and subgroup analyses, particularly in special populations, are expected to help optimize long-term outcomes.