PRISM Study: Real-World Outcomes of First-Line Systemic Therapy for Unresectable HCC: Liver Cancer | May 2026

• PRISM is one of the largest prospective real-world studies evaluating systemic therapy for unresectable hepatocellular carcinoma in routine clinical practice across Japan.

• This analysis reports outcomes from the first 1,000 prospectively enrolled patients, providing important validation of results seen in clinical trials.

• Among evaluable patients, the vast majority received atezolizumab plus bevacizumab (82.8%), while 15.2% received lenvatinib as first-line therapy.

• Median overall survival reached 21.8 months with Atezo+Bev and 20.8 months with lenvatinib, demonstrating excellent real-world outcomes.

• Survival outcomes were numerically better than those reported in the original registration trials, suggesting that careful patient selection, multidisciplinary management, and effective sequential therapy may be improving outcomes in practice.

• Progression-free survival remained consistent with clinical trial data at 7.7 months for Atezo+Bev and 6.7 months for lenvatinib.

• Objective response rates were impressive for both regimens, confirming that real-world effectiveness closely mirrors clinical trial efficacy.

• Sorafenib was rarely used and showed substantially lower response rates compared with modern first-line therapies.

• Grade 3 or higher treatment-related adverse events occurred in approximately 22% of patients, with no unexpected safety concerns.

• Importantly, nearly 50% of patients were able to receive second-line therapy, highlighting the growing importance of sequential treatment strategies in advanced HCC.

• The most common sequencing pattern was:

• Atezolizumab + bevacizumab → lenvatinib

• Lenvatinib → atezolizumab + bevacizumab

• Second-line therapy provided a median progression-free survival of approximately 4 months, while benefit progressively decreased with later treatment lines.

• The study demonstrates that modern systemic therapies can be safely delivered to a broad real-world population, not just highly selected clinical trial patients.

• PRISM also highlights the importance of maintaining liver function and performance status to allow access to sequential therapies, which likely contributes significantly to prolonged survival.

• Future analyses are expected to provide valuable information regarding special populations, including elderly patients, those with impaired liver function, and different molecular or clinical subgroups.

Bottom line: The PRISM study confirms that atezolizumab plus bevacizumab and lenvatinib achieve reproducible real-world outcomes in unresectable HCC, with median overall survival exceeding 20 months and nearly half of patients successfully receiving subsequent lines of therapy.