SBRT for Liver Cancer: Is a New Champion Emerging?

Liver cancer ranks fourth worldwide for cancer deaths, and approximately 6 thousand people are diagnosed annually in Türkiye. Around 90% of cases are hepatocellular carcinoma (HCC). Major causes include hepatitis B and C, excessive alcohol, fatty liver disease, and cirrhosis.

At diagnosis, approximately one-third of patients have tumors confined to the liver and are considered early stage. Treatment options include:

• Surgical resection (the preferred initial approach; potentially curative)
• Liver transplantation (for eligible patients)
• Thermal ablation (RFA [radiofrequency ablation], MWA [microwave ablation]), particularly as an alternative to surgery for small tumors (<3 cm).
• Transarterial chemoembolization (TACE) and radioembolization (TARE) for larger or multifocal tumors unsuitable for ablation.
• Stereotactic body radiotherapy (SBRT), particularly for large tumors or those near blood vessels that are unsuitable for ablation, is increasingly preferred because of high local control and a low adverse-effect profile.

Treatment selection depends on liver function, tumor size, location and number, general health, and the center's experience.

The following image shows early-stage liver cancer treatments other than surgery and transplantation:

The following image shows liver cancer treatments and survival statistics by stage:

What Is SBRT, and Why Does It Matter?

SBRT precisely targets high-dose radiation to a tumor over a few sessions. Recent comparative studies suggest important advantages over other regional liver cancer treatments such as TACE, RFA, and TARE.

Advantages of SBRT in Liver Cancer

Numerous retrospective and prospective studies have investigated SBRT in recent years, comparing it with TACE, RFA, and TARE. Important outcomes include local tumor control, overall and disease-free survival, adverse effects, quality of life, and cost-effectiveness.

1. Retrospective Propensity Score Analyses

SBRT versus TACE:

• Number of patients: 209 patients (125 SBRT, 84 TACE)
• Stage: Early and intermediate stage, Child-Pugh A-B
• Results: Local control at 1 year was 97% with SBRT versus 47% with TACE; at 2 years, 91% versus 23%.
• For local tumor control, SBRT performs 2 to 4 times better than TACE.
• The study noted a particularly dramatic reduction in TACE effectiveness in patients with vascular invasion.

• SBRT versus RFA:

  • Number of patients: 224 patients (63 SBRT, 161 RFA), plus a larger multicenter analysis of 2064 patients (496 SBRT, 1568 RFA)
  • Stage: HCC unsuitable for surgery, predominantly Child-Pugh A-B
  • Results: SBRT provided substantially better local control than RFA, particularly for tumors ≥3 cm or near blood vessels.

2. Prospective Randomized Controlled Trials (RCTs)

• Studies comparing SBRT with TACE:

  • First study: Phase-3, single-center, 40 patients (early and intermediate stages, Child-Pugh A-B).
    • Results: At 1 year, local control was 84% with SBRT versus 23% with TACE (79% received embolization).
  • Second study (TRENDY): Multicenter, phase-2, 28 patients (Child-Pugh A, one tumor each)
    • Results: Time to local recurrence exceeded 40 months with SBRT versus 12 months with TACE. Local control at 1 and 2 years was 100% with SBRT and around 54% with TACE.

• Adding SBRT to sorafenib (RTOG 1112):

  • Number of patients: 177 patients (mostly with extrahepatic disease and vascular invasion)
  • Design: Phase-3, multicenter randomized controlled trial.
  • Results: Adding SBRT to sorafenib increased median overall survival from 12.3 to 15.8 months and significantly improved progression-free survival from 5.5 to 9.2 months.

3. Ongoing or Planned Phase-3 Studies

• A multinational phase-3 study comparing SBRT and TACE (IAEA E33036) is ongoing; results are awaited.
• A phase-3 study comparing SBRT and RFA (NCT05433701) is ongoing.

4. Adverse Effects and Quality of Life

Adverse-effect rates are substantially lower with SBRT than TACE. Grade 3 or higher toxicity ranges from 0-8% with SBRT and may reach 13% with TACE. SBRT also substantially improves quality of life, particularly pain control.

5. Cost-Effectiveness

SBRT is much less expensive than TACE or TARE. By eliminating hospitalization, it offers substantial health-system savings. Total treatment costs, for example, are approximately half those of TACE.

The Future of SBRT: New Combinations and Technology

Important developments aim to improve SBRT effectiveness:

• SMART Technology: MR-guided adaptive radiotherapy improves safety and minimizes damage to surrounding tissue.

• Proton Therapy: Combining SBRT with proton therapy may preserve healthy liver tissue and reduce adverse effects.

• Single-Fraction SBRT: In suitable patients, high-dose treatment in one session offers a fast, effective, and economical option.

• Immunotherapy Combinations: Combining SBRT with immunotherapy may trigger immune responses and improve both local and systemic disease control.

Conclusion and Commentary

SBRT is a prominent option for unresectable HCC, offering excellent local control, improved quality of life, and cost advantages. Multidisciplinary teams should include it in treatment planning. Its advantages should not be overlooked, particularly for large tumors, tumors near blood vessels, or those with macrovascular invasion.

High-quality international multicenter trials are needed to expand and improve SBRT use in liver cancer. Nevertheless, current clinical evidence leaves little doubt that it will increasingly become a standard treatment option.