TY - JOUR
T1 - Therapeutic Underuse and Delay in Hepatocellular Carcinoma
T2 - Prevalence, Associated Factors, and Clinical Impact
AU - Govalan, Rajalakshmi
AU - Luu, Michael
AU - Lauzon, Marie
AU - Kosari, Kambiz
AU - Ahn, Joseph C.
AU - Rich, Nicole E.
AU - Nissen, Nicholas
AU - Roberts, Lewis R.
AU - Singal, Amit G.
AU - Yang, Ju Dong
N1 - Funding Information:
Our study investigated the nationwide prevalence, correlates, and clinical significance of no receipt or delay in HCC treatment. About one quarter of patients did not receive HCC treatment, although the proportion of patients without treatment decreased over time. Among treated patients, therapy was delayed in 18% of patients. In light of the transition from diagnosis to treatment being a complex and multistep process, particularly in early stage patients with HCC, we found multiple factors at different levels were associated with no and delayed treatment. Finally, we found delay in treatment was not associated with shorter OS in landmark analyses, although it showed a mild association with worse OS in patients who had earlier stage HCC and received curative treatment. Underuse of cancer treatment has been reported for several other cancers in the United States, with this issue being more prevalent for low-grade non-Hodgkin lymphoma and less prevalent for germ cell, renal, and colorectal cancers.(28,29) There have been older smaller studies evaluating this question in patients with HCC. A meta-analysis of 24 studies from January 1989 to March 2013 showed 47% of patients with HCC had not received any HCC treatment.(30) Subsequent retrospective cohort studies from an urban safety-net hospital and the Department of Veterans Affairs both reported approximately one-third of patients with HCC failed to receive cancer treatment.(9,30,31) In our study, we found this to be true in a smaller proportion of patients, consistent with observed trends, suggesting increased treatment use over time. The improved treatment use may reflect increasing treatment options with higher efficacy, particularly for those with advanced-stage HCC. Despite this encouraging trend, treatment use remains far lower than other cancers, which might be attributed to 1) higher HCC burden in racial/ethnic minorities who have limited access to medical care, 2) increased medical comorbidities, particularly underlying cirrhosis and hepatic dysfunction precluding cancer treatment, and 3) lower familiarity of providers with HCC treatment algorithms. Indeed, we found Hispanics and Blacks and patients with higher MELD scores were less likely to receive HCC treatment. This is consistent with a recent Surveillance, Epidemiology and End Results registry analysis that showed racial disparities in HCC treatment use among Hispanics and Blacks.(32) Racial/ethnic disparities in the receipt of cancer treatment are well known in multiple other solid organ cancers, with a negative impact on the health outcomes in racial/ethnic minorities.(33) This disparity in treatment are often due to nonclinical factors, and developing strategies to facilitate appropriate cancer care for racial/ethnic minorities may provide an essential means of reducing disparities in cancer treatment.(33) In addition to race/ethnicity, prior studies in other solid organ cancers investigated socioeconomic variations in cancer treatment and patient outcome.(34,35) Our results also highlight the impact of socioeconomic status on HCC treatment receipt, which might stem from variation in access to care (primary care, ambulatory care visits, subspecialist referrals) and quality of cancer treatment.
Funding Information:
Supported by the American College of Gastroenterology (Junior Faculty Development Award), United States Department of Defense (CA191051), Cedars‐Sinai Medical Center (Clinical Scholar award), Huiying Foundation, and National Institutes of Health (R01 MD12565 and U01 CA230694).
Publisher Copyright:
© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases
PY - 2022/1
Y1 - 2022/1
N2 - Prognosis of hepatocellular carcinoma (HCC) could be affected by lack of or delayed therapy. We aimed to characterize the prevalence, correlates, and clinical impact of therapeutic underuse and delay in patients with HCC. Patients with HCC diagnosed between 2010 and 2017 were analyzed from the United States National Cancer Database. Logistic regression analysis identified factors associated with no and delayed (>90 days after diagnosis) HCC treatment. Cox proportional hazards regression with landmark analysis assessed the association between therapeutic delay and overall survival (OS), accounting for immortal time bias. Of 116,299 patients with HCC, 24.2% received no treatment and 18.4% of treated patients had delayed treatment. Older age, Black, Hispanic, lower socioeconomic status, earlier year of diagnosis, treatment at nonacademic centers, Northeast region, increased medical comorbidity, worse liver dysfunction, and higher tumor burden were associated with no treatment. Among treated patients, younger age, Hispanic, Black, treatment at academic centers, West region, earlier tumor stage, and receipt of noncurative treatment were associated with treatment delays. In multivariable Cox regression with a landmark of 150 days, patients with and without treatment delays had similar OS (adjusted hazard ratio [aHR], 1.01; 95% confidence interval [CI], 0.98-1.04) with a median survival of 33.7 vs. 32.1 months, respectively. However, therapeutic delay was associated with worse OS in patients who had tumor, nodes, and metastases (TNM) stage 1 (aHR, 1.06; 95% CI, 1.01-1.11) or received curative treatment (aHR, 1.12; 95% CI, 1.05-1.18). Conclusion: One-fourth of patients with HCC receive no therapy and one-fifth of treated patients experience treatment delays. Both were associated with demographic, socioeconomic, and clinical characteristics of patients as well as facility type and region. The association between therapeutic delay and survival was stage and treatment dependent.
AB - Prognosis of hepatocellular carcinoma (HCC) could be affected by lack of or delayed therapy. We aimed to characterize the prevalence, correlates, and clinical impact of therapeutic underuse and delay in patients with HCC. Patients with HCC diagnosed between 2010 and 2017 were analyzed from the United States National Cancer Database. Logistic regression analysis identified factors associated with no and delayed (>90 days after diagnosis) HCC treatment. Cox proportional hazards regression with landmark analysis assessed the association between therapeutic delay and overall survival (OS), accounting for immortal time bias. Of 116,299 patients with HCC, 24.2% received no treatment and 18.4% of treated patients had delayed treatment. Older age, Black, Hispanic, lower socioeconomic status, earlier year of diagnosis, treatment at nonacademic centers, Northeast region, increased medical comorbidity, worse liver dysfunction, and higher tumor burden were associated with no treatment. Among treated patients, younger age, Hispanic, Black, treatment at academic centers, West region, earlier tumor stage, and receipt of noncurative treatment were associated with treatment delays. In multivariable Cox regression with a landmark of 150 days, patients with and without treatment delays had similar OS (adjusted hazard ratio [aHR], 1.01; 95% confidence interval [CI], 0.98-1.04) with a median survival of 33.7 vs. 32.1 months, respectively. However, therapeutic delay was associated with worse OS in patients who had tumor, nodes, and metastases (TNM) stage 1 (aHR, 1.06; 95% CI, 1.01-1.11) or received curative treatment (aHR, 1.12; 95% CI, 1.05-1.18). Conclusion: One-fourth of patients with HCC receive no therapy and one-fifth of treated patients experience treatment delays. Both were associated with demographic, socioeconomic, and clinical characteristics of patients as well as facility type and region. The association between therapeutic delay and survival was stage and treatment dependent.
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U2 - 10.1002/hep4.1795
DO - 10.1002/hep4.1795
M3 - Article
C2 - 34558830
AN - SCOPUS:85113414268
SN - 2471-254X
VL - 6
SP - 223
EP - 236
JO - Hepatology Communications
JF - Hepatology Communications
IS - 1
ER -