Time trend of pancreatic cancer mortality in the Western Pacific Region: age-period-cohort analysis from 1990 to 2019 and forecasting for 2044

Pancreatic cancer is characterized by poor prognosis, with an overall 5-year survival rate of approximately 10% [1]. The global burden of pancreatic cancer has more than doubled over the past 25 years and now poses a serious medical problem worldwide [2]. The Western Pacific Region is one of the six World Health Organization (WHO) regions and is home to more than a quarter of the world’s population [3]. During the past few decades, the societies and economies of Western Pacific countries/territories have developed, leading to longer life expectancies [4]. The Western Pacific Regional Action Plan for the Prevention and Control of Noncommunicable Diseases 2014–2020 was endorsed by member states in 2013 to avoidable mortality due to noncommunicable diseases in the Western Pacific region [5]. However, the proportion of elderly individuals is growing faster than any other age group in the Western Pacific Region, which will lead to a high cancer burden.

Population aging is one of the important social characteristics in the Western Pacific Region [4]. Pancreatic cancer is typically a disease of older people, and age has been identified as an independent risk factor for pancreatic cancer patients [6]. Although there is ongoing research into pancreatic cancer burden, few studies have analyzed the time trends of pancreatic cancer mortality in Western Pacific countries/territories. Advances in the diagnosis and treatment of pancreatic cancer have been made over the past few years, but we still confront various health challenges. Under these circumstances, assessing, monitoring and comparing progress among pancreatic cancer patients in Western Pacific countries/territories are critical for cancer prevention and adjustment of strategies of treatment. Published studies have explored the trends in the disease burden of pancreatic cancer in some regions and countries [7‐9]. However, studies focused on the age, period and birth cohort effects on pancreatic cancer mortality and predicting future trends remain lacking.

In this article, we conducted a systematic analysis based on the Global Burden of Disease Study (GBD) 2019 to explore the time trends of pancreatic cancer mortality in Western Pacific Region from 1990 to 2019, analyze the age, period, and cohort effects on mortality, and predict mortality to 2044, aiming to provide new insight into regional health.

Cancer is a serious medical and public health problem worldwide, and cancer mortality is becoming an important indicator of progress toward sustainable development goals. In this study, we used an age-period-cohort model to assess the time trends of pancreatic cancer mortality in the Western Pacific Region and predicted the future situation. In 2019, the Western Pacific Region accounted for a high proportion of global pancreatic cancer deaths and may increase in the future, emphasizing the impact of pancreatic cancer burden in this region of the globe. Based on regional situations and global experiences, countries/territories in the Western Pacific Region should develop targeted strategies aimed at high-risk pancreatic cancer populations.

During the past 30 years, the burden of pancreatic cancer was higher in high SDI countries and lower in low SDI countries [12]. Higher pancreatic cancer incidence and mortality in high SDI countries may be due to population aging and lifestyle choices that increase exposure to risk factors, such as obesity and diabetes [12]. For countries with large populations, there were significant increases in DALYs of pancreatic cancer mainly due to population growth and aging. Moreover, high-income countries have great accuracy of cancer-related deaths in databases due to a well-established cancer registry, while low-income and middle-income countries have inadequate access to high-quality cancer data [21‐23]. Thus, the differences in the accuracy of data registries influenced the reliability of some analyses in such low- and middle-income countries. The differences in epidemiological accuracy across countries should be given more attention in the future.

Death cases and ASDR of pancreatic cancer were higher in men than in women in the Western Pacific Region over the past 30 years, which was similar to the global level [24]. Females have a lower incidence of pancreatic cancer and may be less likely to be exposed to some risk factors for pancreatic cancer, such as smoking or factors related to hormonal effects [12]. The global age-standardized prevalence of tobacco use in males (32.7%) is nearly five times that in females (6.62%) [25]. Since 1990, some countries in the Western Pacific Region have not had significant reductions in the prevalence of daily smoking among males [26]. The incidence and death of pancreatic cancer in women may be more attributable to metabolic factors. The worldwide prevalence of overweight and obesity was found to be higher in older females than in older males [27, 28]. However, most countries/territories in the Western Pacific Region have a lower prevalence of obesity.

Smoking is a recognized risk factor for various cancers [1, 29, 30]. Despite a significant decline in the prevalence of smoking since 1990, population growth has led to a significant increase in the total number of smokers worldwide [25]. Cigarettes produce a variety of carcinogens, including tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, and volatile organic compounds [31]. We found that the age-standardized deaths attributable to smoking increased slightly during the past 30 years, and it was still higher than the age-standardized deaths attributable to the two metabolic factors. The Western Pacific Region is home to one-third of the global smoking population, and some countries have a large number of smokers [25, 32]. Despite tobacco control campaigns in many member states, the current rate of tobacco reduction in the Western Pacific is not fast enough to meet the 2025 target [32]. The Framework Convention on Tobacco Control entered into force in 2005, and it redefined approaches to tobacco control and use [33]. Although there has been some regional and national progress in tobacco use and control in recent years, social factors may contribute to the increased disease burden attributable to smoking. We found that population growth and aging are important factors in the increase in pancreatic cancer DALYs, which was similar to the finding from GBD 2015 Tobacco Collaborators: unless progress in reducing tobacco use can be substantially accelerated, population growth is poised to heighten the disease burden associated with smoking [26].

The age effect increased from the youngest to the oldest age group. Several characteristics of aging are very similar to specific cancer hallmarks [34]. Pancreatic cancer has been considered an age-related disease because the cancer appears to share many features with aging, including genomic instability, telomere wear, epigenetic changes, and metabolic alterations [35]. As time goes on, increased exposure to environmental and behavioral factors (such as smoking) may contribute to the chronic accumulation of DNA damage that increases the probability of cancer. Senescent cells in human bodies can manifest as a senescence-associated secretory phenotype, which can secrete various cytokines and growth factors to drive tumorigenesis, including pancreatic cancer [35, 36].

The period effect showed that the mortality risk of pancreatic cancer markedly increased in the Western Pacific Region during the study period. During the past few decades, risk factors for pancreatic cancer have continued to increase among populations. First, the prevalence of smoking has increased; in 2019, male smoking rates were above 20% in more than 150 countries [25, 26]. Among populations over 15 years old, countries with the highest prevalence of tobacco use were mostly in Asia and Oceania [25]. At present, Western Pacific countries are in a critical period of social progress and economic development. People may smoke to relieve pressure and obtain a soothing mood beacuse nicotine causes an acute mood “boost”, including an increased positive effect and a decreased negative effect [37]. Moreover, the westernization of diet and lifestyle in Western Pacific countries may contribute to an increased risk of pancreatic cancer. Dietary patterns changed from a predominantly plant-based diet to a high-energy diet and animal-based foods in some Western Pacific countries [38‐40]. The consumption of energy-dense foods such as meat, snacks, and beverages increased, resulting in high BMI and hyperglycemia.

Similar to the period effect, more exposure to risk factors from the early birth cohort to the latest cohort can contribute to pancreatic cancer burden. We noticed that the cohort rate ratio slightly decreased since the cohort was born in 1985 (from 1.47 in 1985 to 1.37 in 2000). In the latest birth cohort, people can receive better science and health education, and access to medical knowledge is also more abundant. Health awareness has improved among younger people, and they may devote more attention to healthy lifestyles and cancer prevention.

We also predict that the number of future deaths from pancreatic cancer in ten Western Pacific countries will continue to increase. This may be related to the increase in population size and change in population structure in the future. The trends of pancreatic cancer mortality across the Western Pacific Region suggested that these countries should implement stronger measures to reduce the disease burden of pancreatic cancer. Countries that had relatively good performance in cancer prevention and reducing mortality can serve as a reference for others, emphasizing primary health care, scientific education and early cancer screening. In some countries where the population continues to grow and the population is aging, more attention will be needed in the health of high-risk populations and early cancer screening. At present, the main treatments for pancreatic cancer include surgery, chemotherapy and immunotherapy [41]. Some new therapeutic strategies, such as chemotherapy combined with immunotherapy, may improve clinical outcomes for pancreatic cancer patients in the future [42].

This study has many limitations. First, the accuracy of the GBD estimates was limited by the quality and availability of each country’s registration system. For some countries/territories without detailed cancer data sources, GBD estimates were mainly generated from modeling processes, neighboring locations and predictive covariates, which may result in potential substantial uncertainty [43]. The reported high mortality in high-income countries might be partly due to robust systems for determining the cause of cancer death and accurate diagnostic data in registration databases. Some low-income countries cannot provide accurate and adequate data on pancreatic cancer mortality due to incomplete health care systems. Thus, the estimates are very likely to substantially underestimate cancer mortality in low-income countries. This hinders the estimates of the actual disease burden in some places. Next, the age-period-cohort model was conducted in a period of five years due to the 5-year intervals in the GBD 2019, which might smoothen some variations in age, period and birth cohort effects. Future work should focus on more primary data on pancreatic cancer mortality, which might include data from registration databases, cancer centers and longer-term cohort studies. This means that more attention should be given to establishing integrative disease surveillance systems to capture pancreatic cancer-related incidence and mortality, especially in developing countries. Considering that the burden of pancreatic cancer varies by age, sex, country and region, the mortality data should also be classified according to more dimensions in the future. The economic burden caused by pancreatic cancer should also be given more attention.

Pancreatic cancer is an important cause of mortality, and pancreatic cancer deaths continue to increase in the Western Pacific Region. Much of this increase was due to increases in population growth, aging and exposure to risk factors. Our data analysis of pancreatic cancer mortality in Western Pacific Region is limited by the accuracy of data collection in several countries/territories, which needs to be further improved in the future. Modifiable pancreatic cancer risk factors, including behavioral factors and metabolic factors, need to be changed in the Western Pacific region by joint efforts of all countries/territories. Effective cancer prevention approaches and novel anticancer therapy strategies will be essential to achieve the aims of reducing the mortality of pancreatic cancer.