The COVID-19 pandemic significantly strained healthcare systems globally, impacting access to and delivery of oncologic care. While the pandemic's effect on various cancers has been studied, its impact on hepatocellular carcinoma (HCC) management remains largely unclear. HCC is a significant global health concern, representing a substantial portion of primary liver cancers and a leading cause of cancer-related deaths. This study aimed to assess the pandemic's effect on TTI for HCC in the US using the National Cancer Database (NCDB), a comprehensive resource capturing a significant portion of newly diagnosed cancers. The study hypothesized that the pandemic would lead to increased TTI for HCC, and sought to identify patient and hospital factors predictive of extended treatment intervals. The importance of this research lies in understanding the pandemic's potential to exacerbate existing healthcare disparities and inform strategies to mitigate such effects in the future. Understanding the impact on HCC, a particularly challenging cancer to manage, is crucial for optimizing patient outcomes during crises and beyond. This study is unique in its use of the NCDB to perform a nationwide analysis, adding a crucial piece to the understanding of the pandemic's effects on HCC management, which was lacking in previous research.

Prior research has shown significant declines in cancer screenings and encounters during the pandemic across various cancer types, including breast, colorectal, prostate, and melanoma cancers. These delays have been linked to worse prognoses. Studies have explored the pandemic's effect on breast, colon, and prostate cancer care, but its national impact on HCC management in the US remained unstudied until this current research. The existing literature highlighted the potential for oncologic treatment delays to negatively affect patient overall survival. This lack of specific research on HCC necessitated the current study to fill this gap in knowledge and understanding of the pandemic’s impact on HCC care.

This retrospective study utilized data from the NCDB, a nationwide database encompassing approximately 72% of newly diagnosed cancers in the US. The study included patients diagnosed with clinical stages I-IV HCC from 2017 to 2020. Patients were categorized into "Pre-COVID" (2017-2019) and "COVID" (2020) cohorts. TTI was defined as the number of days between diagnosis and treatment initiation (ablation, liver resection, systemic therapy, or radiation). Liver transplantation was excluded due to the complexity of its allocation process. Covariates included patient demographics (age, sex, race, ethnicity), socioeconomic factors (insurance status, income, education, residency), and hospital-specific factors (travel distance, facility type, location). The Mann-Whitney U test compared TTI between the cohorts, and logistic and negative binomial regression models evaluated factors associated with increased TTI and treatment delays (>90 days). The study used backward selection in the multivariate analysis with a significance level of p<0.05.

The study identified 23,922 patients with HCC during the study period (18,673 pre-COVID, 5249 COVID). A statistically significant but not clinically meaningful shorter median TTI was observed during the COVID year (49 days) compared to the pre-COVID years (51 days) for any first-line treatment. This shorter TTI was observed across various treatment modalities including ablation, systemic therapy, and radiation, but not surgery. Multivariate analysis revealed that Black race, Hispanic ethnicity, and uninsured/Medicaid/Other Government insurance were significantly associated with increased TTI and treatment delays. Specifically, the odds ratios for delayed treatment were higher for Black patients (1.172) and Hispanic patients (1.121) compared to white and non-Hispanic patients, respectively. Patients with Medicare or other government insurance also had significantly increased odds of delayed treatment compared to those with private insurance. Patients treated at academic facilities also showed a higher risk of increased TTI and delayed treatment. A sub-analysis showed that patients who received liver transplantation had a shorter median TTI during the COVID year compared to the pre-COVID years (64 vs 121 days). This finding is likely attributable to factors that are not accounted for in the database. The number of HCC diagnoses dropped by 12.2% in 2020 compared to previous years.

The findings suggest that despite the pandemic's strain on healthcare systems, the initiation of HCC treatment was not significantly delayed nationally. The slightly shorter TTI observed for some treatment modalities during the COVID year may be attributable to a shift towards outpatient treatments (systemic therapy, radiation) and alternative treatment strategies recommended by national societies to mitigate COVID-19 exposure risks. However, the significant disparities observed among vulnerable populations highlight the pandemic's potential to exacerbate existing healthcare inequalities. These findings align with previous research demonstrating racial and socioeconomic disparities in HCC treatment access and times to treatment. The pandemic may have further amplified these inequities, suggesting a need for targeted interventions to ensure equitable access to timely HCC care for all populations. The study's findings are consistent with some single-institution studies on other cancers, showing minimal changes in TTI, potentially due to continued treatment efforts in those settings. However, multicenter studies showed larger variations among different centers.

This study demonstrates that while national efforts mitigated the impact of the COVID-19 pandemic on TTI for HCC overall, significant disparities persisted among vulnerable populations. The shorter TTI for some treatment modalities may reflect shifts toward outpatient treatments and alternative approaches to limit COVID-19 exposure. Future research should focus on understanding and addressing these persistent healthcare inequities to ensure equitable access to timely HCC care during public health emergencies.

The study's reliance on the NCDB, which includes only CoC-accredited hospitals, may limit the generalizability of findings and introduce hospital-based sampling bias. The annual-based analysis, due to the NCDB's data resolution, might not fully capture the nuanced effects of the pandemic, which began in early 2020. The NCDB lacks data on transarterial chemoembolization, an alternative treatment strategy used during resource-constrained periods. Furthermore, the study didn't examine the pandemic's impact on HCC screening practices, which could influence TTI. Despite these limitations, the study provides valuable insights into national trends in HCC treatment access and highlights the need for addressing health disparities.