Diagnostic and Therapeutic Delays in Patients With Hepatocellular Carcinoma

Authors: Ashwin Rao MD1, Nicole E. Rich MD, MS1,2, Jorge A. Marrero MD, MS1,3, Adam C. Yopp MD2,4, and Amit G. Singal MD, MS1,2,3
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  • 1 Department of Internal Medicine,
  • | 2 Harold C. Simmons Comprehensive Cancer Center,
  • | 3 Department of Population and Data Sciences, and
  • | 4 Department of Surgery, UT Southwestern Medical Center and Parkland Health and Hospital System, Dallas, Texas.

Background: Delays in diagnosis and treatment have been reported for many cancers, with resultant stage migration and worse survival; however, few data exist in patients with hepatocellular carcinoma (HCC). These data are of particular importance in light of the COVID-19 pandemic, which has caused disruptions in healthcare processes and may continue to impact cancer care for the foreseeable future. The aim of our study was to characterize the prevalence and clinical significance of diagnostic and treatment delays in patients with HCC. Methods: We performed a retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and July 2017 at 2 US health systems. Diagnostic and treatment delays were defined as >90 days between presentation and HCC diagnosis and between diagnosis and treatment, respectively. We used multivariable logistic regression to identify factors associated with diagnostic and treatment delays and Cox proportional hazard models to identify correlates of overall survival. Results: Of 925 patients with HCC, 39.0% were diagnosed via screening, 33.1% incidentally, and 27.9% symptomatically. Median time from presentation to diagnosis was 37 days (interquartile range, 18–94 days), with 120 patients (13.0%) experiencing diagnostic delays. Median time from HCC diagnosis to treatment was 46 days (interquartile range, 29–74 days), with 17.2% of patients experiencing treatment delays. Most (72.5%) diagnostic delays were related to provider-level factors (eg, monitoring indeterminate nodules), whereas nearly half (46.2%) of treatment delays were related to patient-related factors (eg, missed appointments). In multivariable analyses, treatment delays were not associated with increased mortality (hazard ratio, 0.90; 95% CI, 0.60–1.35); these results were consistent across subgroup analyses by Barcelona Clinic Liver Cancer stage and treatment modality. Conclusions: Diagnostic and therapeutic delays exceeding 3 months are common in patients with HCC; however, observed treatment delays do not seem to significantly impact overall survival.

Submitted July 25, 2021; final revision received November 19, 2021; accepted for publication November 23, 2020. Published online May 28, 2021.

Author contributions: Study concept and design: Singal. Data acquisition: Rao, Rich. Data analysis and interpretation: Rich, Singal. Funding acquisition: Singal. Administrative, technical, and material support: Singal. Study supervision: Singal. Drafting of manuscript: Rao, Rich, Singal. Critical revision of manuscript for important intellectual content: All authors.

Disclosures: Dr. Marrero has disclosed serving on a data safety monitoring board for AstraZeneca and receiving consulting fees from Glycotest. Dr. Singal has disclosed serving on advisory boards for and receiving consulting fees from Wako Diagnostics, Roche, Exact Sciences, Glycotest, Bayer, Eisai, Exelixis, Bristol Myers Squibb, Merck/Genentech, and TARGET-Pharmasolutions, and receiving consulting fees from GRAIL. 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 article was supported by the NCI of the NIH under award number R01 MD12565 (to A.C. Yopp and A.G. Singal) and NIH NCI U01 CA230694 (to A.G. Singal).

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

Correspondence: Amit G. Singal, MD, MS, Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Boulevard, POB 1, Suite 420, Dallas, TX 75390-8887. Email: amit.singal@utsouthwestern.edu

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