Comparing the efficacy of immune checkpoint inhibitors with and without microwave ablation in advanced hepatocellular carcinoma in real-world clinical practice: A retrospective cohort study.

Immune checkpoint inhibitors (ICIs) are widely used in the treatment of hepatocellular carcinoma (HCC). Microwave ablation (MWA), a form of thermal ablation, may elicit systemic immune responses and could potentially augment the clinical activity of ICIs, particularly in advanced disease. The present study retrospectively assessed 52 eligible patients with limited progression or oligometastatic disease treated between January 2022 and January 2024 with either ICIs alone or ICIs plus MWA. A total of 21 patients received the combination regimen (predominantly programmed cell death protein 1 inhibitors), and 31 received ICI monotherapy. The recorded baseline characteristics did not suggest notable between-group imbalances; however, key tumor burden descriptors were incompletely captured, and residual confounding cannot be excluded. The objective response rate (ORR) and disease control rate (DCR) were 9.7 and 51.6% with ICIs alone, respectively, vs. 28.6 and 81.0% with ICIs plus MWA. The DCR was higher in the combination group (P=0.031), whereas the between-group difference in ORR was not statistically significant (P=0.133) compared with the monotherapy group. Median overall survival (OS) was 11.0 months with monotherapy and 16.8 months with combination therapy (log-rank P=0.008). In the multivariable Cox analysis, the combination therapy was associated with improved OS (adjusted HR=0.176; 95% CI, 0.048-0.642; Wald P=0.008); however, given the small sample size and limited number of OS events, this adjusted HR may be imprecise and sensitive to model specification and should be interpreted as exploratory. The median progression-free survival (PFS) was 4.0 vs. 9.0 months (log-rank P<0.001), consistent with the multivariable model (adjusted HR=0.270; 95% CI, 0.122-0.595; Wald P=0.001). There was not a clear unexpected safety pattern observed, but safety comparisons were descriptive only and underpowered. In the present retrospective cohort of selected patients with advanced HCC and limited progression/oligometastatic disease, ICIs plus MWA was associated with longer PFS and OS compared with ICIs alone. The interpretation is limited by the small sample size, potential residual confounding and model instability. The direction of benefit was consistent across Kaplan-Meier and Cox analyses, although the adjusted OS effect estimate may be imprecise. The present study was registered on ClinicalTrials.gov on 03 September 2024 (trial no. NCT06581497).