Neoadjuvant Immunotherapy for Hepatocellular Carcinoma Is Associated with Improved Survival After Hepatectomy: A Matched Analysis of the 2017 to 2022 National Cancer Database

Background: Effects of neoadjuvant immunotherapy (NIT) before liver resection are not well-described in hepatocellular carcinoma (HCC). Survival and R0 resection rates in HCC patients undergoing curative-intent resection with or without NIT were evaluated. Methods: A retrospective study of stage I-III HCC patients undergoing hepatectomy from the 2017–2022 National Cancer Database was performed. Patients receiving NIT were exactly matched 1:3 to non-NIT patients by clinical stage. Primary outcomes were margin positivity, 30- and 90-day mortality, and overall survival. Results: After matching 510 patients, 97 received NIT and 291 did not (non-NIT). Resections included segmental (178, 45.9%), lobar (149, 38.4%), and extended hepatectomy (61, 15.7%). The NIT group included ablation (6, 6.2%), radiation (25, 25.8%), and Y90 (18, 18.6%). The non-NIT group included 124 (42.6%) chemotherapy, 23 (7.9%) chemotherapy plus ablation, 31 (10.7%) chemotherapy plus radiation, four (1.4%) radiation, and 109 (37.5%) upfront surgery. NIT patients were treated more at high-volume (41.2% vs. 0%) and academic/research centers (85.4% vs. 50.5%). NIT R0 resection rates were higher (97.9% vs. 93.2%, p = 0.009). Median survival was higher in the NIT group (59.1 vs. 50.4 months, p = 0.002); 30- and 90-day mortality were similar. NIT was not independently associated with improved survival in multivariable Cox regression (HR 0.73, 95% CI [0.35, 1.55]), although the effect estimate indicates a protective effect may be present. Conclusions: NIT was associated with higher R0 resection rates and overall survival without increasing short-term mortality in selected patients at high-volume academic centers, but was not independently associated with survival when adjusting for confounders. As we continue to see increasing use of immunotherapy in the neoadjuvant setting, these findings should be considered hypothesis-generating and warrant prospective validation before widespread adoption for HCC.