Atezolizumab Plus Bevacizumab for Advanced Hepatocellular Carcinoma with Macroscopic Vascular Invasion: An Inverse Probability of Treatment Weighted Analysis

<b>Background/Objectives</b>: Management of hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) varies between systemic immunotherapy and locoregional approaches. We compared atezolizumab plus bevacizumab (Atezo-Bev) with locoregional therapy in treatment-naïve patients. <b>Methods</b>: We conducted a retrospective cohort study of patients with image- or biopsy-proven HCC and MVI, Child-Pugh A/B, and ECOG 0-1 who received first-line Atezo-Bev or locoregional therapy (transarterial chemoembolization [TACE] with or without external-beam radiotherapy [RT]). Inverse probability of treatment weighting (IPTW) minimized baseline imbalances. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Modified RECIST assessed radiologic response, and major adverse events were classified using Society of Interventional Radiology criteria. <b>Results</b>: We analyzed 475 patients (Atezo-Bev, <i>n</i> = 191; locoregional therapy, <i>n</i> = 284). Baseline characteristics were similar, and IPTW achieved covariate balance. Median OS was 9.3 months with Atezo-Bev and 10.8 months with locoregional therapy; after IPTW, OS remained comparable (hazard ratio [HR] 0.95; 95% CI 0.76-1.19; <i>p</i> = 0.635). Median PFS was 6.0 versus 4.1 months, favoring Atezo-Bev; this persisted after IPTW (HR 0.64; 95% CI 0.52-0.79; <i>p</i> < 0.001). Objective response rates were similar (45% vs. 48%; <i>p</i> = 0.49). Major adverse events occurred in 11% of patients in both groups. Subgroup analyses showed no OS differences and a consistent PFS advantage with Atezo-Bev. <b>Conclusions</b>: In HCC with MVI, first-line Atezo-Bev achieved longer PFS than locoregional therapy, with comparable OS and safety, supporting Atezo-Bev as a valid and effective first-line option for disease control while locoregional modalities remain relevant within multidisciplinary care.