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. 2021 Nov 2;113(11):1531-1541.
doi: 10.1093/jnci/djab079.

The Mortality and Overall Survival Trends of Primary Liver Cancer in the United States

Yi-Te Lee  1   2 , Jasmine J Wang  2   3 , Michael Luu  4 , Mazen Noureddin  5   6 , Kambiz Kosari  6 , Vatche G Agopian  7   8 , Nicole E Rich  9 , Shelly C Lu  3   5 , Hsian-Rong Tseng  1   2 , Nicholas N Nissen  3   6 , Amit G Singal  9 , Ju Dong Yang  3   5   6
Affiliations

The Mortality and Overall Survival Trends of Primary Liver Cancer in the United States

Yi-Te Lee et al. J Natl Cancer Inst. .

Abstract

Background: Recent trends of hepatocellular carcinoma (HCC) mortality and outcome remain unknown in the United States. We investigated the recent trends of primary liver cancer (excluding intrahepatic cholangiocarcinoma) mortality and HCC stage, treatment, and overall survival (OS) in the United States.

Methods: The National Center for Health Statistics Database was analyzed to investigate the trend of primary liver cancer mortality. We analyzed the Surveillance, Epidemiology, and End Results 18 Database to assess the temporal trend of tumor size, stage, treatment, and OS of HCC. We investigated the association between HCC diagnosis year and OS using Cox regression analysis. All statistical tests were 2-sided.

Results: During 2000-2018, liver cancer mortality rates increased until 2013, plateaued during 2013-2016 (annual percent change = 0.1%/y, 95% confidence interval [CI] = -2.1%/y to 2.4%/y, P = .92), and started to decline during 2016-2018 (annual percent change = -1.5%/y, 95% CI = -3.2%/y to 0.2%/y, P = .08). However, mortality continues to increase in American Indian and Alaska Native, individuals aged 65 years or older, and in 33 states. There was a 0.61% (95% CI = 0.53% to 0.69%, P < .001) increase in localized stage HCC and a 0.86-mm (95% CI = -1.10 to -0.62 mm, P < .001) decrease in median tumor size per year. The 1-year OS rate increased from 36.3% (95% CI = 34.3% to 38.3%) to 58.1% (95% CI = 56.9% to 59.4%) during 2000-2015, and the 5-year OS rate almost doubled from 11.7% (95% CI = 10.4% to 13.1%) to 21.3% (95% CI = 20.2% to 22.4%) during 2000-2011. Diagnosis year (per year) (adjusted hazard ratio = 0.96, 95% CI = 0.96 to 0.97) was independently associated with OS in multivariable analysis.

Conclusions: Primary liver cancer mortality rates have started to decline in the United States with demographic and state-level variation. With an increasing detection of localized HCC, the OS of HCC has improved over the past decades.

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Figures

Figure 1.
Figure 1.
Age-adjusted primary liver cancer (excluding intrahepatic cholangiocarcinoma) mortality trends, 2000-2018, by sex, age, and race or ethnicity in the National Center for Health Statistics Database. A) Overall primary liver cancer mortality trends. B) Primary liver cancer mortality trends by sex. C) Primary liver cancer mortality trends by age. D) Primary liver cancer mortality trends by race or ethnicity. Error bars represent the 95% confidence intervals. AI and AN = American Indian and Alaska Native; API = Asian and Pacific Islander.
Figure 2.
Figure 2.
State-specific age-adjusted primary liver cancer mortality rates (excluding intrahepatic cholangiocarcinoma) and average annual percentage changes (AAPC) during 2000-2018 in National Center for Health Statistics Database. A) State-specific AAPC of primary liver cancer mortality rates during 2000-2018. B) State-specific mortality rates of primary liver cancer in 2000. C) State-specific mortality rates of primary liver cancer in 2016. D) State-specific mortality rates of primary liver cancer in 2018. aIndicates age-adjusted mortality rate in 2000 were not available. Earliest reported mortality rate was 2001 in WY, which was used to calculate AAPC in (A) and map 2000 mortality rates in (B). PY = person-years.
Figure 3.
Figure 3.
Trends of hepatocellular carcinoma (HCC) tumor stages (2000-2016) and median tumor sizes (2004-2016) in Surveillance, Epidemiology, and End Results 18 Database. A) Trends of HCC tumor stages during 2000-2016. B) Trends of median tumor sizes during 2004-2016. Error bars represent the 95% confidence intervals.
Figure 4.
Figure 4.
Trends of 1-, 3-, 5-year overall survival (OS) of hepatocellular carcinoma (HCC) patients by tumor stages and receipt of curative treatments in Surveillance, Epidemiology, and End Results 18 Database. A) Trends of 1-, 3-, and 5-year OS of overall HCC patients. B) Trends of 1-, 3-, and 5-year OS of HCC patients with localized disease. C) Trends of 1-, 3-, and 5-year OS of HCC patients with regional disease. D) Trends of 1-, 3-, and 5-year OS of HCC patients with distant disease. E) Trends of 1-, 3-, and 5-year OS of HCC patients receiving curative treatment. F) Trends of 1-, 3-, and 5-year OS of HCC patients receiving noncurative treatment. Error bars represent the 95% confidence intervals.
Figure 5.
Figure 5.
Improvement in overall survival of hepatocellular carcinoma (HCC) diagnosed in 2015 compared with HCC diagnosed in 2000 in Surveillance, Epidemiology, and End Results 18 Database. Adjusted hazard ratio of the diagnosis year 2015 with the diagnosis year of 2000 as a reference group. Error bars represent the 95% confidence intervals.
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