SBRT Versus Surgical Resection for Small HCC

Stereotactic Body Radiotherapy (SBRT) Versus Surgical Resection in Patients With Small Hepatocellular Carcinoma: A Phase III, Open-label, Randomized Controlled Trial

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related incidence and mortality in China and represents a major public health challenge. Surgical resection is the most commonly used curative treatment for HCC and can provide favorable long-term outcomes. However, resection is associated with substantial perioperative morbidity, and its applicability is limited in certain patient populations, including those with recurrent disease, those who have undergone conversion therapy, and those with significant coexisting medical conditions.

Advances in radiotherapy technology and the development of highly precise delivery techniques have led to the increasing use of stereotactic body radiotherapy (SBRT) in the management of HCC, particularly in patients with small tumors. Randomized controlled trials conducted by our group have shown that, in patients with recurrent small HCC, SBRT provides superior local tumor control compared with radiofrequency ablation. These findings suggest that SBRT may represent a potentially curative treatment option for selected patients with small HCC.

On the basis of this evidence, the present study is designed to compare the efficacy and safety of surgical resection and SBRT in patients with small HCC. Patients with a solitary tumor measuring 5 cm or less in maximum diameter will be randomly assigned to undergo either surgical resection or SBRT. The primary end point of the study is overall survival. This trial aims to define the relative benefits and risks of these two treatment strategies and to provide high-quality evidence to inform clinical decision making and future guideline recommendations.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Procedure: Resection; Radiation: Stereotactic body radiotherapy (SBRT)

• Study Type: Interventional
• Enrollment (Estimated): 312
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Minshan Chen, PhD, MD; Phone Number: +86 13902241061; Email: chenmsh@sysucc.org.cn
• Study Contact Backup: Name: Yaojun Zhang, PhD, MD; Email: zhangyuj@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 to 75 years, with no restriction on sex;
2. Clinically or pathologically diagnosed hepatocellular carcinoma, according to the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2024 edition);
3. A solitary tumor with a maximum diameter of ≤5 cm, for which treatment is indicated;
4. No radiologic evidence of macrovascular invasion, distant metastasis, or lymph node metastasis;
5. Treatment-naïve or previously treated patients are eligible, provided that they are deemed suitable for both surgical resection and radiotherapy by a multidisciplinary team (MDT) and do not require concomitant systemic therapy at enrollment;
6. For patients with recurrent disease, recurrence must occur at least 1 year after prior curative treatments;
7. Previously treated patients must not have received systemic therapy within 6 months before enrollment;
8. In previously treated patients, tumor size must be assessed according to RECIST version 1.1 at enrollment;
9. A normal liver volume of ≥700 cc, with an estimated future liver remnant volume of >40% after resection;
10. A Karnofsky performance-status score of ≥90;
11. Child-Pugh class A liver function;
12. An estimated life expectancy of more than 6 months;
13. Adequate organ function, defined as follows: white-cell count ≥3.5×10⁹/L, absolute neutrophil count ≥1.5×10⁹/L, platelet count ≥75.0×10⁹/L, hemoglobin ≥90 g/L; serum albumin ≥28 g/L; total bilirubin ≤1.5 times the upper limit of normal (ULN), alanine aminotransferase or aspartate aminotransferase ≤2.5 times the ULN; serum creatinine ≤1.5 times the ULN or creatinine clearance >60 mL per minute; and no severe concomitant organic disease;
14. The ability to understand the study procedures and to provide written informed consent before the initiation of any study-specific procedures, with agreement to receive treatment and follow-up according to the study protocol.

Exclusion Criteria:

1. Severe dysfunction of major organs, including the heart, lungs, or kidneys; active infection other than viral hepatitis; or other serious concomitant conditions that preclude tolerance of either surgery or radiotherapy;
2. Contraindications to surgical resection or radiotherapy;
3. A history of other malignant tumors, with the exception of nonmelanoma skin cancer, carcinoma in situ of the cervix, or previously cured prostate cancer, nasopharyngeal carcinoma, breast cancer, or early-stage laryngeal cancer;
4. A history of multiple abdominal surgeries or liver or other solid-organ transplantation;
5. Previous radiotherapy to the upper abdomen;
6. Pregnancy or breastfeeding;
7. Any other condition that may interfere with patient enrollment or the assessment of study outcomes;
8. Refusal to comply with the follow-up requirements of the study protocol or refusal to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Resection; Patient receive surgical resection	Procedure: Resection; Surgical resection serves as the control treatment in this study
Experimental: SBRT; Patient receive SBRT	Radiation: Stereotactic body radiotherapy (SBRT); The SBRT dose ranges from 33 to 54 Gy and is delivered in three fractions on alternate days, with treatment completed within one week. This study enrolls patients with small hepatocellular carcinoma, defined as a solitary tumor with a maximum diameter of ≤5 cm, and compares the efficacy of SBRT with that of surgical resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	time from random assignment to death from any cause	time from random assignment to death from any cause, assessed up to 100 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	time from random assignment to tumor progression or death fromany cause	time from random assignment to tumor progression or death fromany cause, assessed up to 100 months
LPFS	time from random assignment to local tumor progression or death fromany cause	time from random assignment to local tumor progression or death fromany cause, assessed up to 100 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: January 16, 2026
• First Submitted That Met QC Criteria: January 27, 2026
• First Posted (Actual): February 2, 2026

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 27, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: HCC; SBRT; Resection
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: B2025-806-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD are available from the corresponding author (Minshan Chen and Yaojun Zhang) by request.
• IPD Sharing Time Frame: Beginning 6 months and ending 2 years after the publication of results
• IPD Sharing Access Criteria: For academic discussion purposes, investigators who are interested in this study may contact the study team by email to request the study protocol, the statistical analysis plan, and other relevant materials.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No