Abstract
Background
Survival for Primary Liver Cancer (PLC) has been investigated in Australia, but limited work has been conducted on the burden for people with different socioeconomic status, region of residence, causes of PLC, and culturally and linguistically diverse (CALD) backgrounds. This study aimed to cover this gap in the literature by investigating PLC survival with the aforementioned factors.
Methods
This study linked four administrative datasets: Victorian Cancer Registry, Admitted Episodes Dataset, Emergency Minimum Dataset, and Death Index. The cohort was all cases with a PLC notification within the Victorian Cancer Registry between 01/01/2008 and 01/01/2016. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test was used to compare the difference in survival between subgroups. The Cox proportional hazard model was used to explore factors associated with PLC survival.
Results
The 1-, 3- and 5-year survival rates were 50.0%, 28.1% and 20.6%, respectively, with a median survival of 12.0 months (95% confidence interval (CI): 11.0 – 12.9 months). Higher survival was associated with younger age, hepatocellular carcinoma, and higher socio-economic status. People born in Asian, African, and American regions had higher survival than those born in Australia and New Zealand. Cases with viral hepatitis as an identified aetiology had higher survival than those whose PLC was related to alcohol consumption (hazard ratio=1.52, 95% CI: 1.19 – 1.96), diabetes and fatty liver disease (hazard ratio=1.35, 95% CI: 1.08 – 1.68).
Conclusion
Survival outcomes for people diagnosed with PLC were still poor and affected by many factors. Asian and African cases had better survival than Australian and New Zealand patients as PLC in Asian and African cases was mostly caused by viral hepatitis. Metropolitan areas were associated with a higher survival than rural areas, not only due to accessibility to surveillance and healthcare services but also because the majority of overseas-born patients reside in metropolitan areas.
Highlights
- • PLC mortality rate increased by 184% from 1982 to 2014, making it the fastest increasing cause of cancer death in Australia.
- • PLC caused by viral hepatitis had higher survival time than PLC caused by ARLD, diabetes or MAFLD.
- • CALD patients with PLC showed better survival outcomes their non-CALD counterparts.
- • Metropolitan and higher socioeconomic factors were associated with higher PLC survival.
1
Introduction
Primary liver cancer (PLC) is the sixth most commonly occurring cancer and second leading cause of cancer death in the world . PLC incidence and mortality rates have been increasing in many countries . It is the most rapidly increasing type of cancer in the USA , with the age-standardised incidence rate per 100,000 people increasing from 4.9 in 1999 to 8.7 in 2015 . Northern and Western European countries have also experienced increasing trends of incidence and mortality in recent years . In Australia, the age standardised incidence and mortality rates increased by 306% and 184% respectively from 1982 to 2014 , making it the fastest increasing cause of cancer mortality in this country . The 5-year survival rate of hepatocellular carcinoma (HCC) – the most common form of PLC, accounting for 80% of all cases – was 20% in the USA in 2016 , 18% (result from a meta-analysis) in Asia and 20.9% in Australia in 2017 . Left untreated, just 17.5% (result from a meta-analysis) of HCC patients survive after the first year of diagnosis . The low survival rate of PLC was due to the fact that it was mostly diagnosed at late stages, which limited the treatment options with curative intent (liver transplant, resection, or ablation) for this type of cancer. Advanced-stage PLC patients were mostly eligible for non-curative treatments, which include transarterial chemoembolisation, selective internal radiation therapy and systemic therapy .
Several factors are associated with increased risk of PLC and liver cirrhosis is the most common factor . Cirrhosis is predominantly caused by chronic infection with the hepatitis B virus (HBV) and/or the hepatitis C virus (HCV) . Other risk factors, including diabetes, alcohol-related liver disease (ARLD), and metabolic associated fatty liver disease (MAFLD) also contribute to the development of liver cirrhosis, and thereby increase the risk of PLC . Australia is a strongly multicultural country with 30% of the population (7.6 million people) born overseas . With the estimated HBV prevalence in East Asian and Sub-Saharan Africa region of 7.3% and 7.9–15.4%, respectively, compared to the prevalence of 1.0% in Australia , together with the fact that the number of people migrating from these countries to Australia is expected to increase in the future , this will contribute to increasing incidence of PLC in Australia.
PLC survival has been investigated in Australia, but limited work has been conducted to understand the burden for people of different socio-economic status and culturally and linguistically diverse (CALD) backgrounds. A data linkage study in 2007 reported higher incidence rates of HCC amongst people born in Asian and European countries compared to those born in Australia . A national study and two studies in Victoria compared survival of HCC patients from different ethnic backgrounds and regions of birth. However, the region of residence (rural vs metropolitan) was not considered in two studies and socio-economic status of patients was not investigated in any of these three studies. Another study estimated the survival time of HCC but only in patients with HBV and HCV, and estimated survival from the first hospitalisation for HCC instead of HCC notification . The authors reported improved survival for patients born in the Asia-Pacific region compared to Australian born patients. A recent study reported survival time for all types of cancer, and concluded there was a lower risk of liver cancer death for people born in non-English speaking countries compared to native English speaking patients . However, the categorisation of patients based on English as the first spoken language might not accurately reflect the diversity of culture backgrounds of the patients.
Factors that contribute to improved survival may be related to the differences in PLC aetiologies amongst birth regions . Whilst viral hepatitis is the most common risk factor for PLC in Asia, ARLD is the leading cause of PLC in the USA and Europe , especially in Eastern European countries . Furthermore, the survival disparities could also be partly due to more intensive monitoring of HBV, HCV and liver health in some ethnic groups, resulting in liver cancer diagnosed at earlier stages . However, this is likely to be concentrated in large urban/metropolitan centres. Other factors affecting survival include socio-economic status, cultural behaviour and immigration experience . It is, therefore, important to generate robust evidence regarding survival of PLC for CALD patients as this can be used to support more targeted clinical services to address identified health inequities. This study aims to investigate PLC survival by CALD backgrounds (with a focus on region of birth), region of residence, socio-economic status, and PLC aetiologies of the patients.
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