In patients with intermediate‑to‑advanced hepatocellular carcinoma, Child‑Pugh A or early B liver function and ECOG performance status 0‑1, what are the median overall survival and progression‑free survival when transarterial chemoembolization (TACE) is combined with chemo‑immunotherapy (atezolizumab plus bevacizumab) compared with TACE alone?

TACE Combined with Chemo-Immunotherapy: Survival Statistics

Current Evidence Does Not Support Routine Combination of TACE with Chemo-Immunotherapy

The 2025 EASL guidelines explicitly state that intra-arterial therapy must NOT be combined with systemic tyrosine-kinase inhibitors in intermediate-stage HCC with large tumor burden (Level 2 evidence, strong recommendation, 82% consensus), and this caution extends to immunotherapy combinations due to lack of proven benefit and significant safety concerns. 1

Survival Data for TACE Alone (Standard of Care)

• TACE monotherapy in intermediate-stage HCC achieves a median overall survival of 19-31 months in large randomized controlled trials, with response rates of 36-42%. 2

• Historical meta-analyses demonstrate TACE improves survival from 16 to 20 months in patients with intermediate HCC compared to untreated controls. 2

• A recent international study showed 5-year overall survival of 22.5% with TACE, with better outcomes in Child-Pugh A (29.4%) versus Child-Pugh B patients (12.8%). 2

Survival Data for Atezolizumab Plus Bevacizumab Alone (Without TACE)

• Atezolizumab plus bevacizumab as first-line systemic therapy achieves a median overall survival of 19.2 months and median progression-free survival of 6.9 months in patients with unresectable HCC, Child-Pugh A, and ECOG 0-1. 3, 4

• The objective response rate is 27.3% with atezolizumab plus bevacizumab versus 11.9% for sorafenib. 3

Limited Data on TACE Combined with Chemo-Immunotherapy

Retrospective Studies (Not Definitive)

• A 2025 retrospective cohort study of TACE + lenvatinib + PD-1 inhibitor (n=35) versus TACE + lenvatinib alone (n=80) in intermediate-stage HCC exceeding up-to-7 criteria showed:
  • Median PFS: 10.0 months versus 5.7 months (P=0.002) 5
  • Median OS: 21.0 months versus 16.2 months (P=0.096, not statistically significant) 5
  • Time to progression to macrovascular invasion or extrahepatic spread: 12.0 months versus 7.5 months (P=0.007) 5
  • Grade 3-4 adverse events: 48.6% versus 42.5% (P=0.546) 5

Ongoing Randomized Trial (Results Pending)

• The LEAP-012 trial is evaluating TACE plus lenvatinib plus pembrolizumab versus TACE plus placebo in 950 patients with intermediate-stage HCC, with dual primary endpoints of overall survival and progression-free survival. 6

• Results are not yet available, and this represents the only adequately powered randomized trial addressing this question. 6

Critical Safety Concerns with TACE Plus Bevacizumab

• A 2015 randomized controlled trial of TACE plus bevacizumab was stopped prematurely for safety reasons due to severe septic (n=8 versus n=3) and vascular complications (n=9 versus n=0) almost exclusively in the bevacizumab group. 7

• Median survival was worse in the TACE plus bevacizumab group (5.3 versus 13.7 months, P=0.195), reaching statistical significance in Child-Pugh A patients (7.3 versus 26.5 months, HR 2.6, P=0.049). 7

• Bevacizumab cannot be recommended as adjuvant treatment to TACE based on this trial showing no improvement in radiologic response or survival but severe and lethal complications. 7

Hepatic Function Deterioration with Repeated TACE

• After each TACE session, hepatic function deteriorates from Child-Pugh A to B in 9-14% of patients and ALBI grade 1 to 2 in 18-21% of patients. 2, 1

• Repeated TACE-induced liver function decline can preclude the benefit of subsequent systemic therapy, as liver function is a critical prognostic factor for immunotherapy efficacy. 2, 1

• Prior phase III trials combining TACE with sorafenib (SPACE, TACE-2) failed to demonstrate any survival advantage (Level 2 evidence). 1

Guideline-Recommended Treatment Algorithm

For Liver-Confined Intermediate-Stage HCC

1. TACE monotherapy should be preferred to systemic therapy when selective approach is feasible (low tumor size/number, non-infiltrative pattern, preserved portal flow). 2, 1

2. Perform contrast-enhanced CT or MRI at 4-6 weeks post-TACE and evaluate with mRECIST criteria. 1

3. Complete or partial response → continue TACE on-demand. 1

4. Stable disease after one TACE → repeat TACE once more. 1

5. Progressive disease or stable disease after two TACE sessions → declare TACE refractoriness and switch to systemic immunotherapy (atezolizumab plus bevacizumab). 1, 4

Critical Contraindications

• Do not combine TACE with systemic immunotherapy in patients with large tumor burden or Child-Pugh B/C liver function due to unacceptably high risk of hepatic decompensation. 1, 8

• Confirm preserved liver function (Child-Pugh A) and ECOG 0-1 before initiating immunotherapy after TACE failure. 1, 4

Common Pitfalls to Avoid

• Do not continue TACE concurrently with immunotherapy; sequential therapy is the recommended approach. 1

• Do not treat more than 50% of liver volume in a single TACE session to limit post-procedural liver failure. 1

• Screen for esophageal varices before initiating atezolizumab plus bevacizumab, as untreated high-risk varices are a contraindication. 4

• Avoid TACE in Child-Pugh C patients, as liver toxicity and decompensation rates are unacceptably high. 8