Since the release of the 2022 edition of the Primary Liver Cancer Diagnosis and Treatment Guidelines, numerous high-quality studies—both domestic and international—have advanced the field of hepatocellular carcinoma (HCC), especially in diagnosis, staging, and treatment. Research reflecting China's real-world clinical settings has provided important theoretical guidance for the management of liver cancer. Building on accumulated clinical experience, the National Health Commission has organized expert teams to revise the guidelines, culminating in the publication of the 2024 edition, which introduces comprehensive updates across screening, diagnosis, and treatment.To provide professional insights into the latest revisions concerning interventional and local therapies, Oncology Frontier invited Professor Zhengqiang Yang from the Cancer Hospital Chinese Academy of Medical Sciences to share his expert interpretation.
I. Ablation Therapy: Evolving Techniques and Focus on Recurrence Prevention
Common ablation techniques for hepatocellular carcinoma (HCC) include radiofrequency ablation (RFA), microwave ablation (MWA), percutaneous ethanol injection (PEI), and cryoablation (CRA). Among these, MWA stands out for its high efficiency and shorter ablation time, which reduces the “heat sink effect” commonly associated with RFA. This makes MWA particularly effective for tumors adjacent to major blood vessels, hypervascular tumors, and larger lesions, where more thorough ablation is required.
A landmark 12-year real-world multicenter study led by Professor Ping Liang’s team at the PLA General Hospital evaluated MWA in 2,354 patients with tumors ≤5 cm. The results showed 1-, 5-, and 10-year overall survival (OS) rates of 96.4%, 63.9%, and 41.1%, respectively. These findings demonstrate that MWA provides reliable long-term efficacy with a favorable safety profile for early-stage liver cancer.
Another multicenter retrospective study included 514 patients and used propensity score matching to compare 257 patients treated with MWA and 257 with laparoscopic liver resection (LLR) for solitary HCC tumors measuring 3–5 cm. The study found comparable efficacy between the two treatments: the median OS was 99.0 months for the MWA group and 93.8 months for the LLR group, indicating that MWA offers a non-surgical alternative with equivalent outcomes for appropriately selected patients.
Updated Recommendation: Adjuvant Therapy After Ablation Based on IMbrave050
The 2024 edition of the guidelines introduces, for the first time, a recommendation for adjuvant therapy after ablation to prevent recurrence and metastasis in liver cancer patients—based on the findings of the IMbrave050 trial.
IMbrave050 is a phase III, global, open-label, randomized clinical study comparing atezolizumab plus bevacizumab versus active surveillance in patients who had undergone curative resection or ablation for hepatocellular carcinoma (HCC). The study demonstrated a significant improvement in recurrence-free survival (RFS) with the combination therapy:
- RFS: 22.1 months (atezo + bev) vs. 21.4 months (surveillance)
- Hazard ratio (HR): 0.72
- 95% CI: 0.56–0.93; P = 0.012
These findings provide strong evidence supporting the use of atezolizumab + bevacizumab as adjuvant treatment following ablation, marking a notable advance in recurrence prevention strategies.
II. TACE: A More Refined and Comprehensive Therapeutic Strategy
As the understanding and technique of transarterial chemoembolization (TACE) evolve, so too do its indications and applications. The 2024 guidelines incorporate multiple updates supported by high-level evidence in line with modern principles of evidence-based medicine.
Key Updates Include:
- Expanded Indications and Refined Contraindications: The updated guidelines now include recommendations for using TACE in patients with portal vein branch tumor thrombus and emphasize the importance of dynamic liver function assessment throughout treatment planning.
- Clearer Technical Classifications: The guidelines differentiate between conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE), highlighting the latter’s superior tumor response rates in specific clinical scenarios.
- Inclusion of Radioembolization (TARE): Yttrium-90 microsphere-based transarterial radioembolization (TARE) is newly listed in the appendix, providing a forward-looking perspective on its potential clinical integration.
- Emphasis on Precision TACE: A “refined TACE” concept is introduced, advocating for stratified treatment objectives tailored to tumor size, anatomical location, and patient liver function.
- Expansion of TACE-Based Combination Therapy: TACE is now positioned as a core component of multimodal strategies, including combinations with portal vein iodine-125 seed stents, RFA, radiotherapy, surgery, hepatic arterial infusion chemotherapy (HAIC), and systemic therapies.
Clinical Highlight: TACE + Ablation Outperforms Ablation Alone for 3–7 cm Tumors
For non-resectable CNLC stage Ib or IIa patients with solitary or multiple tumors ranging from 3 to 7 cm, the guidelines now recommend TACE combined with ablation over ablation alone (Level 2 evidence, Recommendation B).
This recommendation is supported by a phase III randomized trial conducted between October 2006 and June 2009, which enrolled 189 early-stage HCC patients. Patients were randomly assigned to receive either TACE + RFA (N = 94) or RFA alone (N = 95). Long-term follow-up demonstrated that the combination therapy group achieved significantly improved overall survival (OS) and recurrence-free survival (RFS) compared to RFA monotherapy, affirming the synergistic benefit of this integrated approach.
Would you like me to continue with the next set of updates on TACE combined with radiotherapy and other modalities?
The combination of TACE and external beam radiotherapy (EBRT) has been shown to significantly improve local tumor control in patients with large, localized HCC. In the 2024 guideline, this combined approach is especially recommended for patients with CNLC stage III liver cancer, including those with portal vein or inferior vena cava tumor thrombus, and those with extrahepatic metastases. The supporting evidence comes from a meta-analysis that included 25 studies (11 of which were randomized controlled trials) and a total of 2,577 patients. Among these, eight studies involved patients with stage III or IV disease, and 18 involved patients with portal vein tumor thrombus (PVTT). Compared to TACE alone, TACE combined with radiotherapy demonstrated significantly better outcomes in both overall survival and tumor response.
Another key update in the guidelines highlights the value of TACE as a downstaging tool for liver transplantation. TACE can effectively reduce tumor burden, enabling some patients who initially exceed liver transplant criteria to meet eligibility standards. This approach improves the transplant rate and lowers post-transplant recurrence, with outcomes comparable to those of patients initially within standard criteria. A prospective multi-regional study using the UNOS-DS criteria showed that TACE achieved a downstaging success rate of over 80%. Moreover, the study found that TACE and Yttrium-90 radioembolization had similar efficacy when used as initial downstaging strategies. Two-year survival rates following liver transplantation reached as high as 95%, reinforcing the clinical value of this approach.
The guidelines also recognize the growing role of TACE combined with targeted and immunotherapy in conversion therapy for unresectable hepatocellular carcinoma. A retrospective study conducted from November 2018 to December 2020 involved 62 patients with uHCC who received a triple combination of lenvatinib, PD-1 inhibitors, and TACE. Of these patients, 35 were classified as BCLC-C, 21 as BCLC-B, and 6 as BCLC-A. The study found an objective response rate of 80.6% by investigator assessment and 77.4% by blinded independent review. Notably, 33 patients (53.2%) were successfully converted to resectable status, with 29 ultimately undergoing surgery. Among those, 16 achieved pathological complete response, and 24 showed major pathological response. These results underscore the potential of integrated treatment strategies to significantly improve surgical conversion rates in intermediate and advanced HCC.
In patients with a high risk of recurrence following surgery, the 2024 guidelines recommend adjuvant TACE to detect and treat residual or recurrent lesions early. This recommendation applies to cases involving tumor rupture before surgery, tumors larger than 5 cm, multiple lesions, microvascular or macrovascular invasion, positive margins, poor differentiation, or elevated tumor markers that do not return to normal postoperatively. A meta-analysis of ten randomized controlled trials involving a total of 1,216 patients demonstrated that the combination of liver resection and adjuvant TACE significantly reduced both mortality and recurrence compared with resection alone. The hazard ratio for death was 0.66, and for recurrence was 0.70, both with strong statistical significance.
For patients with portal vein tumor thrombus or massive tumors, especially those with involvement of the main portal vein trunk, the guidelines introduce a new recommendation: TACE combined with hepatic arterial infusion chemotherapy (HAIC) using the mFOLFOX regimen. A retrospective study covering 155 patients treated between January 2011 and December 2016 compared the outcomes of those receiving cTACE plus HAIC (86 patients) versus cTACE alone (69 patients). The analysis revealed that the combination therapy offered better overall survival and progression-free survival outcomes. This further confirms the therapeutic benefit of using a dual-modality approach in complex, high-tumor-burden cases.
For patients with moderate to high tumor burden or those who exhibit resistance or poor response to TACE, the 2024 guidelines emphasize the need for early combination with molecular targeted therapies. This recommendation is supported by a multicenter retrospective observational study involving 1,719 patients with unresectable, liver-limited HCC. Among them, 313 patients received TACE combined with sorafenib, while 1,406 were treated with TACE alone. The study aimed to assess whether combining TACE with targeted therapy improved clinical outcomes. Results showed that patients with intermediate tumor burden or favorable liver function (low ALBI scores) had improved survival when treated with the combination regimen.
In addition to this, the new guidelines highlight that TACE combined with molecular targeted therapy outperforms targeted therapy alone. This conclusion is based on a phase III, multicenter, randomized controlled trial conducted across 12 hospitals in China from June 2019 to July 2021. The study enrolled 338 patients with advanced primary HCC who had either not received any prior treatment or experienced recurrence after curative surgery without further postoperative therapy. Patients were randomized into two groups: lenvatinib plus TACE (n = 170) and lenvatinib monotherapy (n = 168). The results demonstrated that the combination group achieved significantly higher objective response rates (ORR) as well as longer median overall survival (mOS) and median progression-free survival (mPFS) compared to lenvatinib alone, confirming the superior efficacy of the combination strategy.
Further strengthening this recommendation are the findings from CHANCE001, the largest real-world multicenter study in China to date examining TACE combined with targeted immunotherapy. The study confirmed that TACE plus targeted immunotherapy significantly improves PFS and OS in patients with intermediate or advanced HCC compared to TACE alone.
Another important study, CHANCE2211, was a national, multicenter, retrospective, real-world study that used propensity score matching to evaluate the efficacy of TACE combined with camrelizumab and apatinib versus TACE alone in patients with HCC. The findings were compelling: in the combination group, progression-free survival reached 13.5 months compared to 7.7 months in the TACE-alone group (hazard ratio = 0.52, 95% CI: 0.37–0.74, P < 0.001). Overall survival was also significantly prolonged in the combination group, reaching 24.1 months (95% CI: 20.0 to not reached) versus 15.7 months (95% CI: 13.2–22.7) in the TACE-alone group (hazard ratio = 0.41, 95% CI: 0.26–0.64, P < 0.001).
III. Expanding Role of Radiotherapy: Growing Evidence Supports Broader Applications
The 2024 edition of the guidelines highlights a progressively expanding role for external radiotherapy (RT) in the treatment of hepatocellular carcinoma, supported by an increasing body of evidence-based data.
One of the key updates is the inclusion of external radiotherapy as a bridging therapy prior to liver transplantation. This recommendation (Level 2 evidence, Recommendation B) is based on findings from a phase II, single-center, single-arm, prospective non-randomized trial involving 38 patients with central-type HCC. All patients received neoadjuvant intensity-modulated radiation therapy (IMRT) followed by surgery. The study aimed to assess the safety and efficacy of preoperative IMRT in this subgroup.
The primary endpoint was the five-year overall survival (OS), while secondary endpoints included tumor response to IMRT, five-year disease-free survival (DFS), and treatment-related adverse events. The results showed that 13 patients (34.2%) achieved a major pathological response, and 5 patients (13.2%) achieved complete pathological remission. At a median follow-up of 45.8 months, the median OS had not yet been reached, with a five-year OS rate of 69.1%. The median DFS was 45.8 months, with a five-year DFS rate of 41.0%. These findings support the feasibility of incorporating radiotherapy as a neoadjuvant strategy to optimize outcomes in transplant-eligible patients.
The guidelines also address a novel and promising approach: combining immune checkpoint inhibitors with stereotactic body radiotherapy (SBRT). Preliminary research suggests that this combination may have synergistic effects, although further high-level evidence is still needed (Level 3 evidence, Recommendation C). A comprehensive meta-analysis of 46 studies involving 7,595 patients with unresectable intermediate to advanced HCC examined seven therapeutic interventions, including sorafenib plus radiotherapy, sorafenib plus HAIC, sorafenib plus TACE, radiotherapy alone, TACE, HAIC, and sorafenib monotherapy.
The analysis revealed that external radiotherapy combined with sorafenib outperformed all other interventions in terms of clinical efficacy for unresectable HCC.
In addition to the meta-analysis findings, a single-arm, open-label, phase II clinical trial was conducted at a single center to evaluate the efficacy of SBRT combined with sintilimab in patients with recurrent or oligometastatic HCC. The study enrolled 25 patients and demonstrated promising early outcomes, suggesting the potential clinical value of this combined immunoradiotherapy approach in selected advanced-stage cases.
Conclusion
The 2024 edition of the Primary Liver Cancer Diagnosis and Treatment Guidelines introduces significant updates to interventional and local therapies, encompassing ablation, transarterial chemoembolization (TACE), and external beam radiotherapy (EBRT).
Ablation therapy remains a key modality for CNLC stage Ia and select Ib cases, with growing evidence supporting its long-term efficacy and safety. Research on technique optimization, particularly for microwave ablation, has matured, and the new guideline includes, for the first time, adjuvant therapy following ablation to prevent recurrence and metastasis, based on the IMbrave050 study.
TACE, as a cornerstone treatment for CNLC stage IIb, IIIa, and select IIIb patients, has seen notable evolution. The updated guidelines underscore the importance of individualized therapy—promoting the concept of precision TACE to reduce treatment heterogeneity—and endorse TACE-based combination therapies involving ablation, radiotherapy, surgery, HAIC, targeted agents, and immunotherapy to enhance treatment efficacy and broaden clinical benefit.
External radiotherapy, once narrowly applied, now plays an increasingly active role. Its indications have expanded to include pre-transplant bridging therapy, and combination regimens with targeted agents or immune checkpoint inhibitors have shown early promise for improving survival in unresectable or oligometastatic HCC. Supported by real-world data and prospective trials, EBRT is now firmly positioned as a valuable component of multidisciplinary care in liver cancer.
Altogether, the updated guidelines reflect a shift toward precision, multimodal, and evidence-based treatment paradigms, offering renewed hope for patients and empowering clinicians with refined tools to improve outcomes across the HCC spectrum.
About the Expert
Professor Zhengqiang Yang Cancer Hospital, Chinese Academy of Medical Sciences
- Chief Physician and Doctoral Supervisor, Department of Interventional Therapy
- Standing Committee Member, Minimally Invasive Therapy Committee, Chinese Anti-Cancer Association
- Standing Committee Member, Tumor Ablation Committee, Chinese Anti-Cancer Association
- Standing Committee Member, Digestive Surgery Branch, Chinese Research Hospital Association
- Executive Committee Member, Interventional Radiology Branch, Chinese Maternal and Child Health Association
- Vice Chair, Peripheral Vascular and Venous Access Branch, Chinese Association of Integrative Medicine
- Executive Committee Member, Minimally Invasive and Interventional Therapy Committee, World Chinese Oncologist Association
- Secretary-General, Interventional Therapy Committee, Beijing Oncology Society
- Committee Member, Academic Committee, Center for Drug Evaluation, National Medical Products Administration (NMPA)
- Member, Gastrointestinal and Pancreatic Disease Branch, Chinese Society of Radiology
- Editorial Board Member, Chinese Journal of Interventional Radiology
- Editorial Board Member, Chinese Journal of Digestive Diseases and Imaging
