What are the indications for Transarterial Chemoembolization (TACE) in Hepatocellular Carcinoma (HCC)?

TACE Indications in Hepatocellular Carcinoma

TACE is the standard first-line treatment for intermediate-stage HCC (BCLC stage B) in patients with preserved liver function (Child-Pugh A or favorable B7), good performance status (ECOG 0-1), large or multifocal tumors, and no macroscopic vascular invasion or extrahepatic spread. 1

Primary Indications

Intermediate-Stage HCC (BCLC Stage B)

• Patients with large or multinodular asymptomatic HCC who maintain excellent liver function and have no evidence of vascular invasion or extrahepatic spread are ideal TACE candidates. 1
• The tumor characteristics include multiple nodules or solitary lesions not amenable to curative therapies (resection, transplantation, or ablation). 1
• TACE extends median survival from approximately 16 months with supportive care to about 20 months. 2, 3

Alternative Indication: Early-Stage HCC

• TACE can be performed in early-stage HCC when curative treatments (resection, transplantation, ablation) cannot be conducted due to compromised liver function, performance status, underlying diseases, portal hypertension, unfavorable tumor location, or poor tumor visibility on ultrasonography. 1
• This represents a pragmatic deviation from guidelines when curative options are technically unfeasible. 1

Bridge to Transplantation

• For liver transplant candidates with anticipated waiting times exceeding 6 months, TACE may be offered to minimize tumor progression risk and serve as a bridge to transplant. 1
• This applies to patients within or potentially exceeding Milan criteria during the waiting period. 1

Essential Patient Selection Criteria

Required Characteristics

• Preserved liver function: Child-Pugh A or Child-Pugh B7 without ascites 1, 2
• Good performance status: ECOG 0-1 1, 2
• No radiologic evidence of main portal vein occlusion (complete thrombosis) 1, 2
• Absence of extrahepatic spread 1
• Adequate renal function: creatinine clearance ≥30 ml/min 1

Tumor Burden Considerations

• While increasing tumor size and number reduce TACE efficacy, the procedure remains indicated for multinodular disease when liver function is preserved. 1
• Superselective TACE can be considered even in patients with compromised liver function when tumors are small and technically accessible. 1

Absolute Contraindications

TACE must not be performed in the following situations: 1, 2

• Decompensated cirrhosis (Child-Pugh B ≥8 or Child-Pugh C), including jaundice, clinical encephalopathy, or refractory ascites 1
• Main portal vein occlusion or hepatofugal blood flow 1, 2
• Extensive tumor with massive replacement of both entire lobes 1
• Untreatable arteriovenous fistula 1
• Bilioenteric anastomosis or biliary stents (high risk of liver abscess) 1
• Creatinine clearance <30 ml/min 1
• ECOG performance status ≥2 2, 4

Expanded Indications in Select Populations

HCC with Vascular Invasion

• In Eastern guidelines, TACE may provide survival benefit in selected patients with locally advanced HCC and portal vein thrombosis when liver function is preserved. 1
• This represents a departure from Western guidelines and requires careful patient selection with superselective technique. 1
• The risk of liver failure increases substantially with macroscopic portal vein invasion, making this a high-risk scenario. 4

Recurrent HCC After Prior Treatment

• TACE is widely used for recurrent HCC following previous curative treatments or prior TACE sessions. 1
• Decision-making adopts metrics from initial treatment guidelines, though well-designed studies for this population are limited. 1

Treatment Technique Selection

Conventional TACE (cTACE) vs. Drug-Eluting Bead TACE (DEB-TACE)

• Both techniques are considered equivalent treatment options. 1, 5
• DEB-TACE with doxorubicin-eluting beads demonstrates less systemic chemotherapy leakage, resulting in fewer side effects while maintaining equivalent efficacy. 1
• DEB-TACE is particularly beneficial for HCC ≥3 cm. 5
• Selective administration with drug-eluting beads minimizes systemic toxicity. 1

When to Repeat or Stop TACE

Repeat TACE Protocol

• Perform repeat TACE "on-demand" with 1-2 month intervals between sessions based on radiological assessment. 2
• Follow-up imaging (CT or MRI) should occur at 4-6 weeks post-procedure using mRECIST criteria. 2

Criteria to Stop TACE

Discontinue TACE after 2-3 unsuccessful sessions showing no radiological response or progressive disease. 2

Additional stopping criteria include: 2

• Liver function deterioration to Child-Pugh B8 or higher
• ECOG performance status worsening to ≥2
• Development of main portal vein thrombosis
• Appearance of extrahepatic spread

Transition to Systemic Therapy

• When TACE fails or disease progresses, transition to systemic therapy with atezolizumab plus bevacizumab or sorafenib/lenvatinib. 2, 5
• The combination of TACE with sorafenib—either sequential or concomitant—cannot be recommended in routine clinical practice based on current evidence. 1

Critical Safety Considerations

Post-Embolization Syndrome

• The most common side effect includes fever, abdominal pain, and nausea, which are generally self-limited. 1, 4

Risk of Liver Failure

• Risk factors for post-procedural liver failure include main portal vein occlusion, obstructive jaundice, underlying liver dysfunction, extensive TACE treating more than half the liver, non-selective TACE, and hepatic arterial occlusion from repetitive procedures. 1
• Even patients with well-preserved liver function require careful assessment when treatment extent is large. 1

Liver Abscess Risk

• Risk increases dramatically in patients with biliary obstruction, bile duct injury from previous surgery, bilioenteric anastomosis, or biliary stenting. 1
• Consider alternative therapies (radioembolization, external beam radiotherapy, systemic therapy) in high-risk patients. 1

Common Pitfalls to Avoid

• Do not perform TACE in patients with Child-Pugh B ≥8, as this dramatically increases mortality risk from liver failure. 1
• Avoid non-selective TACE when superselective catheterization is technically feasible, as this increases complication rates. 1, 5
• Do not continue TACE indefinitely without objective response—establish clear stopping criteria after 2-3 failed sessions. 2
• Recognize that TACE cannot cure intermediate-stage HCC as single-modality treatment—it is palliative with survival benefit. 1