Hepatocellular carcinoma is the sixth most common malignancy and the third leading cause of cancer-related death globally. Despite therapeutic advances over the past decade, most patients are diagnosed at intermediate or advanced stages—largely because conventional ultrasound and alpha-fetoprotein screening miss approximately 30 to 40 percent of early-stage cases. Even among those who undergo successful curative-intent resection, the five-year recurrence rate approaches 70 percent, with early recurrences driven by occult micrometastases and late recurrences arising from underlying chronic liver disease. The rising global burden of metabolic dysfunction-associated steatotic liver disease is further reshaping the epidemiological landscape, adding new complexity to an already challenging clinical picture. Based on these challenges, there is an urgent need for an integrated strategy that addresses the entire care continuum—from early detection through long-term recurrence surveillance—to meaningfully improve patient outcomes.
A team of researchers from the Eastern Hepatobiliary Surgery Hospital at Naval Medical University in Shanghai and the First Affiliated Hospital of Henan University has published (DOI: 10.20892/j.issn.2095-3941.2026.0045) a comprehensive review in Cancer Biology & Medicine (August 2026, Volume 23, Issue 8) outlining a surgery-centered precision management framework for hepatocellular carcinoma. The framework is built on three interconnected pillars—early detection, precision surgery, and recurrence prevention—and synthesizes international evidence, including substantial data from high-volume Asian centers where more aggressive surgical approaches have demonstrated meaningful survival advantages in carefully selected patients.
The review highlights several paradigm-shifting advances. In early detection, multi-parameter models such as the GALAD score—incorporating gender, age, alpha-fetoprotein (AFP), its Lens culinaris agglutinin-reactive fraction (AFP-L3), and des-gamma-carboxy prothrombin (DCP)—and the more cost-effective ASAP score [age, sex, AFP, and protein induced by vitamin K absence or antagonist-II (PIVKA-II)] achieve area under the receiver operating characteristic curve (AUROC) values exceeding 0.85 across various etiologies, significantly outperforming AFP alone. Circulating tumor DNA methylation-based liquid biopsy has shown promise for detecting hepatocellular carcinoma at stages amenable to curative intervention and detecting cases missed by conventional markers. In precision surgery, the China Liver Cancer (CNLC) staging system has shown advantages over the Barcelona Clinic Liver Cancer (BCLC) system, particularly for intermediate-stage patients, with higher homogeneity and monotonicity in survival prediction. Conversion therapy combining immunotherapy with locoregional treatments has expanded surgical opportunities for selected patients with initially unresectable hepatocellular carcinoma. Perhaps most significantly, the randomized phase 2/3 CARES-009 trial showed that perioperative therapywithcamrelizumab (a PD-1 inhibitor) and rivoceranib (a VEGFR-2 inhibitor) significantly improved event-free survival compared with surgery alone in patients with resectable HCC at intermediate or high risk of recurrence. The perioperative group also achieved a major pathological response rate of 35.1%, compared with 7.5% in the surgery-alone group, supporting further investigation of perioperative treatment as a strategy to address occult micrometastatic disease.
The authors said that the traditional approach of treating hepatocellular carcinoma as a series of isolated clinical events is no longer sufficient. "We need to think of this as a continuous care pathway," they explained. "Early detection, surgical precision, and recurrence prevention are not separate steps—they are mutually reinforcing components of a unified strategy. The emerging data on perioperative immunotherapy, particularly the CARES-009 results, suggest that we may be on the cusp of a fundamental shift in how we manage this disease. Our goal is to move from reacting to recurrence to proactively preventing it." They emphasized that integrating circulating tumor DNA-based minimal residual disease monitoring into postoperative surveillance could facilitate dynamic, personalized adjuvant therapy decisions based on real-time molecular evidence rather than static risk factors alone.
This integrated framework has immediate clinical implications. For patients, it means earlier detection through more sensitive blood-based biomarkers, expanding access to curative surgery through conversion therapy and minimally invasive techniques, and more personalized postoperative surveillance tailored to individual risk profiles. For clinicians, the review provides a practical roadmap for multidisciplinary decision-making that incorporates tumor biology, liver function, and patient performance status. The authors note that while much of the evidence comes from Asian centers where hepatitis B virus is the predominant etiology, the principles of precision intervention and active surveillance have broad applicability. Future multicenter prospective studies are needed to validate these approaches in Western populations, where metabolic dysfunction-associated steatotic liver disease and hepatitis C are more common drivers of disease.
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References
DOI
10.20892/j.issn.2095-3941.2026.0045
Original Source URL
https://doi.org/10.20892/j.issn.2095-3941.2026.0045
Funding information
National Natural Science Foundation of China (Grant Nos. 82425049, 82273074, 82372813, 82500794); Shanghai Outstanding Academic Leader Program (Grant No. 23XD1424900); Shanghai Health and Hygiene Discipline Leader Project (Grant No. 2022XD001); National Science and Technology Major Project of the Ministry of Science and Technology of China (Grant Nos. 2024ZD0520500, 2024ZD0520506); China Postdoctoral Science Foundation (Grant No. 2025M771998).
About Cancer Biology & Medicine
Cancer Biology & Medicine (CBM) is a peer-reviewed open-access journal sponsored by China Anti-cancer Association (CACA) and Tianjin Medical University Cancer Institute & Hospital. The journal monthly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China. The journal is indexed in SCOPUS, MEDLINE and SCI (IF 12.4), with all full texts freely visible to clinicians and researchers all over the world.