Factors Associated With Detection and Survival of T1 Hepatocellular Carcinoma in the United States: National Cancer Database Analysis

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  • 1 Division of Digestive and Liver Diseases,
  • 2 Comprehensive Transplant Center,
  • 3 Samuel Oschin Comprehensive Cancer Institute, and
  • 4 Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, West Hollywood, California; and
  • 5 Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas.
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Background: It remains unknown to what extent hepatocellular carcinomas (HCCs) are detected very early (T1 stage; ie, unifocal <2 cm) in the United States. The aim of this study was to investigate the trends and factors associated with very early detection of HCC and resultant outcomes. Methods: Patients with HCC diagnosed from 2004 through 2014 were identified from the National Cancer Database. Logistic regression was used to identify factors associated with T1 HCC detection, and Cox proportional hazard analyses identified factors associated with overall survival among patients with T1 HCC. Results: Of 110,182 eligible patients, the proportion with T1 HCC increased from 2.6% in 2004 to 6.8% in 2014 (P<.01). The strongest correlate of T1 HCC detection was receipt of care at an academic institution (odds ratio, 3.51; 95% CI, 2.31–5.34). Older age, lack of insurance, high Model for End-Stage Liver Disease (MELD) score, high alpha-fetoprotein, increased Charlson-Deyo comorbidity score, and nonsurgical treatment were associated with increased mortality, and care at an academic center (hazard ratio [HR], 0.27; 95% CI, 0.15–0.48) was associated with reduced mortality in patients with T1 HCC. Liver transplantation (HR, 0.27; 95% CI, 0.20–0.37) and surgical resection (HR, 0.67; 95% CI, 0.48–0.93) were independently associated with improved survival compared with ablation. This is the first study to examine the trend of T1 HCC using the National Cancer Database, which covers approximately 70% of all cancer diagnoses in the United States, using robust statistical analyses. Limitations of the study include a retrospective study design using administrative data and some pertinent data that were not available. Conclusions: Despite increases over time, <10% of HCCs are detected at T1 stage. The strongest correlates of survival among patients with T1 HCC are receiving care at an academic institution and surgical treatment.

Submitted February 3, 2020; accepted for publication March 25, 2020.

Author contributions: Study concept: Yang, Singal, Noureddin, Kuo, Ayoub, Sundaram, Kotler, Kim, Todo, Voidonikolas, Brennan, Kosari, Klein, Hendifar, Lu, Nissen, Gong. Study design: Yang. Data acquisition: Yang. Data interpretation: All authors. Manuscript preparation: Yang. Statistical analysis: Luu. Critical revision of the manuscript: Luu, Singal, Noureddin, Kuo, Ayoub, Sundaram, Kotler, Kim, Todo, Voidonikolas, Brennan, Kosari, Klein, Hendifar, Lu, Nissen, Gong.

Disclosures: Dr. Yang has disclosed that he serves as a consultant for Exact Sciences. Dr. Singal has disclosed that he serves as a consultant for Glycotest, Exact Sciences, Wako Diagnostics, TARGET Pharmasolutions, Bayer, Eisai, Bristol-Myers Squibb, Exelixis, and Roche/Genentech. Dr. Noureddin has disclosed that he has received grant/research support from Allergan, Bristol-Myers Squibb, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Novartis, Shire, and Zydus, and he is a scientific advisor for Gilead, Intercept, Pfizer, Novartis, Allergan, Blade, EchoSens North America, Fractyl, OWL, Siemens, Roche Diagnostic, and Abbott. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health (R01 MD12565 and R01 CA222900).

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Correspondence: Ju Dong Yang, MD, MS, Cedars-Sinai Medical Center, 8900 Beverly Boulevard, Los Angeles, CA 90048. Email: judong.yang@cshs.org

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