Therapeutic Underuse and Delay in Hepatocellular Carcinoma: Prevalence, Associated Factors, and Clinical Impact

Abstract

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. (Hepatology Communications 2021;0:1-14).

Barriers to Surveillance for Hepatocellular Carcinoma in a Multicenter Cohort

“…Alternatively, surveillance implementation is 1 step in a larger continuum, and patients who underwent surveillance may have still experienced downstream failures, such as diagnostic delays, therapeutic delays, or underuse of curative treatments. 32 , 33 Third, this may reflect the ongoing debate regarding the effectiveness of HCC surveillance programs, particularly with some studies failing to find an association with improved survival. 34 , 35 , 36 , 37 A large randomized clinical trial in China demonstrated a decrease in HCC-related mortality with surveillance among patients with chronic hepatitis B infection 38 ; however, supporting evidence in patients with cirrhosis is largely limited to cohort studies, which have known limitations, including lead time bias, length time bias, and residual confounding.…”

“…This may explain the high proportion of patients with surveillance-detected HCC despite low proportions with semiannual surveillance. Alternatively, surveillance implementation is 1 step in a larger continuum, and patients who underwent surveillance may have still experienced downstream failures, such as diagnostic delays, therapeutic delays, or underuse of curative treatments . Third, this may reflect the ongoing debate regarding the effectiveness of HCC surveillance programs, particularly with some studies failing to find an association with improved survival .…”

“…Abbreviations: BCLC, Barcelona Clinic Liver Cancer; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); HCC, hepatocellular carcinoma; HCV, hepatitis C virus; SVR, sustained virological response.a Other race category includes Pacific Islander patients and those who identified as more than 1 race.JAMA Network Open | Gastroenterology and HepatologySurveillance AttainmentOver a median (IQR) of 36(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36) months prior to HCC diagnosis, a mean (range by site) of 14.0%(5.3%-33.3%) of patients received semiannual surveillance and 22.3% (14.3%-28.8%) of patients received annual surveillance. The mean (SD) PTC by surveillance was 49.7% (30.8%) (Figure).…”

Hepatocellular Carcinoma Screening in a Contemporary Cohort of At-Risk Patients

“…These data reinforce that screening is only the first step in the cancer care continuum, and patients with early-stage detection must undergo timely curative treatment to have improved survival . Efforts are needed to promote patients receiving high-quality care at multidisciplinary, high-volume settings to reduce issues regarding underuse of curative treatments …”

Time to surgery is not an oncological risk factor in HCC patients undergoing liver resection

“…In the cohort of Rao et al, only 31.3% were treated by liver resection, while in the publication of Signal et al 28% of all patients did undergo surgery demonstrating a limited view on patients with early-stage HCC. Another large study by Govalan et al demonstrated no association between delay in treatment for HCC and worse OS according to the data of 100,000 patients [ 21 ]. Although 38% of the included patients were treated with liver resection, non-curative modalities were also included in this investigation.…”