The Impact of the COVID-19 Pandemic on Hepatocellular Carcinoma Time to Treatment Initiation: A National Cancer Database Study

The COVID-19 pandemic caused unprecedented strain on healthcare delivery, including cancellations/postponements of non-emergent surgeries and rapid transitions to telemedicine. Reports showed substantial declines in cancer screenings and patient encounters across multiple cancer types, raising concern for later-stage diagnoses and worse outcomes. While impacts on breast, colorectal, and prostate cancer care have been studied, national-level effects on hepatocellular carcinoma (HCC) management in the United States were unclear. Given HCC’s global burden as the predominant form of primary liver cancer, this study used the National Cancer Database (NCDB) to assess the annual impact of the COVID-19 pandemic on time to treatment initiation (TTI) for HCC and to identify patient and hospital factors associated with increased treatment intervals.

Prior work during the pandemic documented declines in cancer screenings and encounters (e.g., breast, prostate, melanoma) and patient-reported delays in clinic visits, surgeries, infusions, and imaging. Delays in cancer treatment are associated with worse survival across several cancers. However, before this study, there had been no national assessment of pandemic effects on HCC care delivery in the US. Guidelines from major societies (ACS, AASLD, SAGES/AHPBA, SSO) advocated for continued cancer treatment with resource-aware triage, suggesting possible mitigation of delays. Pre-pandemic literature also documents disparities in HCC treatment delays and access to curative therapies by race/ethnicity and socioeconomic status, indicating that vulnerable populations may be disproportionately affected during crises.

Data source: NCDB (captures ~72% of US cancers from >1500 CoC-accredited facilities). Study cohort: Adults with AJCC clinical stage I–IV HCC diagnosed 2017–2020. 2017 cases staged with AJCC 7th ed.; 2018–2020 with 8th ed. HCC identified by ICD-O-3 topography C22.0 and histology codes 8170, 8140, 8500. Cohorts: Pre-COVID (2017–2019) vs. COVID (2020). Treatments included for TTI analyses: ablation, liver resection, systemic therapy (chemotherapy or immunotherapy), or radiation. Liver transplantation excluded from primary analysis due to allocation confounding; examined in a sub-analysis. Covariates: demographics (age at diagnosis, sex, race, ethnicity), socioeconomic factors (insurance, median household income quartile, educational attainment quartile, metro/non-metro residence), hospital factors (median travel distance ≤14.8 vs >14.8 miles, facility type, region), and comorbidities (Charlson-Deyo score 0, 1, ≥2). Exclusions: missing covariates; missing TTI data; ambiguous first-treatment TTI (equal to more than one modality). Outcomes: Treatment patterns by stage; TTI defined as days from diagnosis to first treatment (most definitive surgery for ablation/resection; minimum days to chemotherapy or immunotherapy for systemic therapy; minimum across modalities for multimodal therapy). Delayed treatment defined as TTI >90 days. Statistics: Baseline comparisons via chi-square. TTI comparisons via Mann-Whitney U. Predictors of increased TTI analyzed with negative binomial regression; predictors of delayed treatment (>90 days) via multivariate logistic regression with backward selection (α=0.05). SAS 9.4 used; significance p<0.05.

- Sample: 23,922 patients with stage I–IV HCC (Pre-COVID n=18,673; COVID n=5,249). Median age 65 years (IQR 60–71); 76.34% male; 74.13% White; 85.66% non-Hispanic. More diagnoses occurred Pre-COVID; 2020 saw a 12.2% drop in HCC diagnoses versus prior years. A higher proportion were age >65 (52.96% vs 46.92%; p<0.0001) and stage IV at diagnosis (16.90% vs 13.91%; p<0.0001) during COVID. - Treatment patterns: In stage I and II, radiation use increased during COVID (stage I: 25.06% vs 21.25%; stage II: 28.72% vs 24.35%) and systemic therapy decreased (stage I: 17.34% vs 24.66%; stage II: 29.55% vs 36.37%). Minimal differences in ablation or resection for early stages; no significant differences for stages III–IV. - TTI overall: Median TTI to any first-line treatment was slightly shorter during COVID vs Pre-COVID (49 vs 51 days; p<0.0001). - TTI by stage: Stage I had shorter TTI during COVID (53 vs 56 days; p=0.0235). Stages II–IV showed no significant differences. - TTI by first treatment modality: Ablation 52 vs 55 days (p=0.0238); Systemic therapy 42 vs 47 days (p<0.0001); Radiation 60 vs 62 days (p=0.0177); Resection 41 vs 41 days (p=0.6887). - Multivariate predictors of increased TTI (negative binomial IRR): Black vs White IRR 1.057 (95% CI 1.022–1.093; p=0.0013); Hispanic vs non-Hispanic IRR 1.045 (95% CI 1.010–1.081; p=0.0104); Insurance: Medicare vs Private IRR 1.047 (95% CI 1.017–1.078; p=0.0023), Uninsured/Medicaid/Other Government vs Private IRR 1.088 (95% CI 1.053–1.123; p<0.0001); Lower income vs ≥$74,063 showed stepwise increases (IRR 1.034 to 1.085; all significant); Academic centers vs community IRR 1.119 (95% CI 1.089–1.150; p<0.0001); West vs Northeast IRR 1.218 (95% CI 1.175–1.262; p<0.0001). COVID year associated with decreased TTI vs Pre-COVID (IRR 0.944; 95% CI 0.919–0.969; p<0.0001). - Predictors of delayed treatment (>90 days; logistic OR): Age >65 OR 0.874 (95% CI 0.810–0.943; p=0.0005); Black vs White OR 1.172 (95% CI 1.065–1.290; p=0.0012); Hispanic vs non-Hispanic OR 1.121 (95% CI 1.023–1.228; p=0.0141); Insurance: Medicare vs Private OR 1.127 (95% CI 1.032–1.230; p=0.0079), Uninsured/Medicaid/Other Government vs Private OR 1.356 (95% CI 1.236–1.487; p<0.0001); Lower income showed stepwise higher odds (OR 1.144, 1.320, 1.385; all significant); Travel distance >14.8 miles OR 1.077 (95% CI 1.006–1.153; p=0.0334); Region: South OR 1.115 (95% CI 1.012–1.229; p=0.0282), West OR 1.771 (95% CI 1.595–1.965; p<0.0001); Academic vs community OR 1.371 (95% CI 1.263–1.488; p<0.0001). COVID year was associated with lower odds of delay vs Pre-COVID (OR 0.896; 95% CI 0.828–0.970; p=0.0065). - Sub-analysis including liver transplantation (first-line in 414/25,182, 1.64%): TTI to transplant was shorter during COVID vs Pre-COVID (64 vs 121 days; p=0.001). No changes in general cohort findings.

Despite a notable reduction in HCC diagnoses during 2020, the US healthcare system maintained timely initiation of HCC treatment, with median TTI slightly shorter during the COVID year and no clinically meaningful delays overall. National guidance from surgical and hepatology societies emphasizing continued cancer treatment with resource-aware triage, along with outpatient feasibility and adjusted dosing/scheduling for systemic therapies, likely mitigated delays—reflected by shorter TTI for systemic therapy and radiation. Resection TTI remained stable, suggesting effective prioritization of surgical care when appropriate. However, treatment at academic centers was associated with increased TTI and higher odds of delay, potentially due to resource reallocation to COVID-19 care. Most concerning, Black and Hispanic patients, those with non-private insurance, and lower-income groups had increased TTI and higher odds of treatment delays, indicating exacerbation of pre-existing disparities during the pandemic. These findings underscore the need to address structural barriers and develop resilient care pathways that protect timely cancer treatment for vulnerable populations, and to further study the pandemic’s effects on HCC screening and stage at presentation.

In a national NCDB analysis, patients diagnosed with HCC during the first COVID-19 year (2020) experienced TTI that was statistically shorter but not clinically different from prior years, with modality-specific reductions for ablation, systemic therapy, and radiation, and stable times for resection. Nonetheless, vulnerable populations (Black, Hispanic, non-privately insured, and lower income) were more likely to have increased TTI and delays. Future efforts should focus on safeguarding timely cancer care during health system disruptions, reducing disparities across the cancer care continuum, and evaluating impacts on HCC screening and stage migration.

Findings are limited to CoC-accredited institutions, introducing potential sampling bias and limiting generalizability. NCDB provides diagnosis year rather than month, so the 2020 cohort includes some pre-pandemic diagnoses; conversely, early 2020 social-distancing measures may have already affected care. The NCDB lacks data on transarterial chemoembolization, an important alternative therapy during resource constraints. The study does not assess HCC screening practices or stage migration directly. Residual confounding is possible despite multivariable adjustments.