Most Liver Cancer Patients in China May Qualify for Tumor-Shrinking Therapy Before Surgery, Survey Finds

Liver cancer remains one of the most formidable challenges in modern oncology, and nowhere is that challenge starker than in China, where more than 367,700 new cases of liver cancer were recorded in 2022, making it the fourth most common cancer diagnosis in the country. With 316,500 deaths in the same year, liver cancer ranked second among all cancer-related deaths. Hepatocellular carcinoma, the dominant form of primary liver cancer, accounts for roughly 75 to 85 percent of these cases. The central tragedy of the disease is timing: most Chinese patients are diagnosed at intermediate or advanced stages, when the tumor has already grown beyond the window in which surgical resection—the only reliably curative option—can be safely performed. A new nationwide survey of senior specialists, published in Holistic Integrative Oncology, now offers the most detailed picture yet of how Chinese physicians are responding to this crisis with an increasingly influential strategy known as conversion therapy.

Conversion therapy, sometimes called downstaging therapy, refers to the use of systemic drugs, local regional treatments, or both, to shrink initially unresectable tumors until they become candidates for curative surgery. The concept has gained momentum in recent years as systemic treatments have improved dramatically. Combinations of anti-angiogenic targeted drugs and immune checkpoint inhibitors now achieve objective response rates of around 30 percent in advanced or unresectable hepatocellular carcinoma, while local therapies such as transarterial chemoembolization (TACE), hepatic artery infusion chemotherapy (HAIC), and radiation therapy have become more effective at reducing tumor volume and controlling tumor thrombus within blood vessels. When these approaches succeed, patients who once had no surgical option can undergo resection, and studies suggest their post-surgical survival can approach that of patients whose tumors were resectable from the start.

To understand how this evolving paradigm is actually being applied, a team led by investigators from the National Cancer Center in Beijing and the China Liver Cancer Study Group Young Investigators conducted a structured survey between January and July 2024. The researchers distributed questionnaires to physicians meeting strict criteria: they had to work at a tertiary hospital, practice in hepatobiliary surgery or interventional radiology, hold the rank of associate chief physician or above, see at least five new hepatocellular carcinoma patients per month, and serve as primary decision-makers for conversion therapy. Ultimately, 120 valid responses were collected from 79 tertiary hospitals across 20 provinces. Nearly 70 percent of respondents were hepatobiliary surgeons and the remainder were interventional radiologists, reflecting the two specialties that dominate conversion therapy decision-making in China’s disease-centered, surgery-led multidisciplinary model.

The headline finding is striking: physicians reported that approximately 51 percent of newly diagnosed patients with stage Ib to IIIa disease, according to the China Liver Cancer Staging (CNLC) system, were selected for conversion or downstaging treatment with the goal of eventual resection. The proportion was highest among patients with stage IIb and IIIa tumors, of whom 52 percent and 59 percent respectively received such treatment. In other words, more than half of newly diagnosed patients in these intermediate stages are now being routed through a treatment pathway designed to convert an impossible operation into a possible one. This represents a profound shift from a decade ago, when most of these patients would have gone directly to palliative local or systemic therapy without any surgical ambition.

Which patients do physicians choose for this aggressive approach? The survey identified three dominant factors. Portal vein tumor thrombus (PVTT)—the invasion of tumor into the main blood vessel draining the liver—was considered by 97 percent of respondents, making it the most widely weighed criterion. Future liver remnant volume, the amount of healthy liver that would remain after resection, and Child–Pugh liver function classification were each cited by 90 percent. Tumor number followed at 89 percent, with extrahepatic metastasis and tumor size each at 88 percent. When physicians rated the importance of each factor on a seven-point scale, extrahepatic metastasis and portal vein tumor thrombus received the highest weights, with 82 percent and 78 percent of relevant respondents scoring them six or above. The typical candidate for conversion therapy, according to the respondents, had Child–Pugh A liver function or well-preserved B7 function, a tumor larger than five centimeters, good performance status, and early or moderate portal vein tumor thrombus.

The prominence of portal vein tumor thrombus reveals a genuine philosophical evolution in the field. Under the Barcelona Clinic Liver Cancer (BCLC) staging system, used widely in Europe and the United States, hepatocellular carcinoma with portal vein invasion is classified as advanced stage C, and systemic therapy is recommended as the only option. Japanese guidelines take a middle path, recommending surgery when thrombus has not invaded first-order portal vein branches. Chinese guidelines classify vascular invasion as stage IIIa and list TACE with or without systemic therapy as the primary treatment, followed by surgery. Yet 72 percent of surveyed physicians considered patients with Vp1/2 thrombus—where tumor invasion remains limited—suitable for conversion therapy, reflecting what the authors describe as a shift from a narrow to a broad concept of conversion intent. The rationale is twofold: modern drug combinations can shrink both the tumor and the thrombus, facilitating complete resection, and the treatment period itself helps identify biologically aggressive tumors that would recur quickly after surgery, sparing those patients a futile operation.

When it comes to the regimens themselves, the survey found overwhelming preference for combination therapy. Approximately 73 percent of patients received a combination of local treatment with targeted therapy and immunotherapy. Within this group, 29 percent received targeted plus immunotherapy with TACE, 26 percent with HAIC, and 18 percent with both local modalities together. Only about 10 percent of physicians used systemic therapy alone. Interventional radiologists were significantly more likely than surgeons to favor quadruple combinations including both TACE and HAIC, while surgeons more often selected systemic therapy alone. The biological logic of these combinations is compelling: anti-angiogenic drugs inhibit the new vessel formation that TACE can paradoxically stimulate, while TACE itself increases expression of immune-suppressive molecules such as CTLA-4 and PD-L1, which immune checkpoint inhibitors then block, restoring anti-tumor immunity. A recent meta-analysis covering 2007 to 2024 reported conversion rates of 5 to 28 percent for systemic therapy alone, 13 to 33 percent for combined local and systemic therapy, and peaks around 35 percent for regimens combining lenvatinib, PD-1 inhibitors, and local treatment.

Drug selection showed a clear winner. Lenvatinib combined with immunotherapy was the preferred systemic backbone for 64 percent of physicians, with 49 percent using the original formulation and 13 percent using generics. The next most popular regimens—bevacizumab biosimilar with sintilimab, and bevacizumab with atezolizumab—trailed far behind at around 11 percent. Physicians explained their choices through a hierarchy of priorities: a higher objective response rate was the foremost consideration for 83 percent, followed by rapid onset of response at 68 percent, adherence to guidelines and consensus documents at 63 percent, and lower tumor progression rate at 58 percent. Lenvatinib-based regimens scored well across efficacy, safety, and practical metrics, including lower bleeding risk, shorter preoperative drug discontinuation times, and easier dose adjustment—considerations that matter enormously when the endpoint is not merely tumor control but a safe operation.

What defines success, and what happens after it? Physicians ranked R0 resectability—the ability to remove all visible tumor with clear margins—as the most important criterion for successful conversion, selected by 96 percent and weighted most heavily. Tumor thrombus regression, adequate future liver remnant volume, achievement of complete or partial radiological response, and tumor stability for more than two months followed. The survey’s estimated overall conversion success rate was approximately 32 percent, but the figure fell sharply with disease stage: 57 percent for stage Ib patients, 42 percent for stage IIa, 35 percent for stage IIb, 28 percent for stage IIIa, and just 15 percent for stage IIIb, where extrahepatic metastases make radical surgery far harder to achieve. Among patients who converted successfully, about 57 percent went on to surgery, and 79 percent of those surgical patients received postoperative adjuvant therapy, most commonly systemic treatment with targeted and immunotherapy combinations.

The authors are candid about the limitations of their work. All surveyed hospitals were tertiary referral centers, so the findings may not generalize to community hospitals. The conversion success rates reflect physician estimates rather than audited patient-level data, and the anonymous cross-sectional design precluded assessing test–retest reliability or comparing respondents with non-respondents. Still, the survey’s value lies in mapping real-world clinical attitudes at a moment when the evidence base consists largely of retrospective studies and small single-arm trials, with randomized controlled data still scarce. By documenting that over half of newly diagnosed intermediate-stage patients in China are now considered candidates for conversion therapy, and by identifying the criteria and regimens that dominate practice, the study provides a foundation for the multicenter collaboration and standardized protocols that the authors say are needed next. For a disease that kills more than 300,000 people a year in China alone, turning initially hopeless diagnoses into curative operations is a goal worth pursuing with both enthusiasm and rigor.

Subject of Research: Physician perceptions and clinical practice of conversion and downstaging therapy for hepatocellular carcinoma in China

Article Title: Physicians’ perceptions of HCC conversion/downstaging therapy: a nationwide survey among tertiary hospital physicians in China

Article References: Bi, X., Liang, X., Tan, G., Zhao, H.-T., Huang, T., Zhao, M., Chen, J., Zhu, X.-D., Xue, J., Sun, H.-C., Cai, J., & China Liver Cancer Study Group Young Investigators(CLEAP) (2026). Physicians’ perceptions of HCC conversion/downstaging therapy: a nationwide survey among tertiary hospital physicians in China. Holistic Integrative Oncology, 5(1), Article 37. https://doi.org/10.1007/s44178-026-00256-x

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00256-x

Keywords: hepatocellular carcinoma, conversion therapy, downstaging, portal vein tumor thrombus, liver cancer, lenvatinib, immunotherapy, TACE, HAIC, surgical resection, China, nationwide survey