Mortality for pancreatic cancer throughout 2003–2022 in the US

Introduction According to the latest statistics from the World Health Organization (WHO), pancreatic cancer is not one of the most common types of cancer, but only ranks 12th on the list of cancers with the highest incidence in the general worldwide population (510,992 new cases per year).[1] However, when analyzing the global mortality rate, the importance of this type of cancer increases considerably, as pancreatic cancer ranks sixth, with a rate of around 4.8% of all cancer deaths.[1] This apparent discrepancy between incidence and mortality is due to a variety of factors, including the lack of effective screening, diagnostic delays due to the appearance of (often non-specific) symptoms only at advanced stages of disease, high aggressive potential, rapid progression and spread, proximity to other vital structures and limited availability of treatment options due to invasiveness, anatomical location, and resistance to therapeutic treatments.[2] In a recent article, Danpanichkul et al[3] used the Global Burden of Disease Study 2019 to provide statistics on the worldwide incidence, deaths, and disability-adjusted life years associated with early-onset pancreatic cancer, and concluded that this form of cancer has increased between 2000 and 2019. Therefore, we planned an additional study to define the 20-year trend in pancreatic cancer mortality in the general US population. Methods We conducted an electronic search on the WONDER (Wide-Ranging, Online Data for Epidemiologic Research) website, an online repository containing all death certificates for the US resident population compiled by the US Centers for Disease Control and Prevention (CDC).[4,5] The search criteria used for our analysis included the year (2003–2022), combined with the International Classification of Diseases 10th Revision (ICD-10) code for pancreatic cancers (C25: malignant neoplasm of the pancreas), sex (males and females), and 10-year age groups. The results of these searches were downloaded as age-adjusted or crude (when appropriate) death rates (per 100,000) for pancreatic cancer. As CDC WONDER is a fully anonymized and publicly available database, ethics committee approval was not required for this study. Results The results of our analysis are summarized in Figure 1. The cumulative, age-adjusted mortality rate for pancreatic cancer (with 95% confidence interval [95% CI]) has increased steadily over the last 20 years, from 10.54 (95% CI, 10.42–10.66) per 100,000 in 2003 to 11.24 (95% CI, 11.03–11.14) per 100,000 in 2022 (+5.7%) (Fig. 1A). A clear deviation from the 20-year trend was observed in 2021 when the age-adjusted mortality rate rose by 3.2% compared to the previous year. Even considering the age-adjusted mortality rate in the last year before the pandemic (ie, 2019), the mortality rate for this cancer type had increased to 11.03 (95% CI, 10.93–11.13) per 100,000 compared to 2003 (+4.6%). The trend in age-adjusted mortality for both sexes from 2003 to 2022 is summarized in Figure 1B. This shows that the age-adjusted death rate for men was consistently higher than for women (between 28.8% and 34.5% higher), but also that the 20-year increase in the mortality rate was higher for men than for women (7.0% vs 4.3%). In both sexes, a peak could be observed again during the coronavirus disease 2021 (COVID-19) pandemic, particularly in 2021, when the age-adjusted death rate increased by 2.7% for men and 3.9% for women compared to 2020. When considering the age-adjusted death rate in the last year before the pandemic (ie, 2019), the mortality rate for this type of cancer still increased by 5.1% for men and 3.7% for women, respectively. The age-adjusted mortality for pancreatic cancer over the last 20 years for the 10-year age groups is summarized in Figure 1C. Notwithstanding the fact that death rates increased in parallel with population aging, the 20-year trend was remarkably different, as the crude death rate did not change or even decreased in younger people (25–34 years: 0%; 35–44 years: −9.7%; 45–54 years: −4.5%), while it steadily increased in older subjects (55–64 years: +9.9%; 65–74 years: +4.4%; 75–84 years: +8.0%; ≥85 years: +5.7%). The fluctuations in 2021 were +8.3% between 25 and 34 years, +4.6% between 35 and 44 years, −4.3% between 45 and 54 years, +1.5% between 55 and 64 years, +0.3% between 65 and 74 years, +3.9% between 75 and 84 years, and +12.8% in the 85 years and older age group.Figure 1.: Mortality for pancreatic cancer in the US between the years 2003 and 2022. (A) Cumulative age-adjusted mortality; (B) age-adjusted mortality between sexes; (C) crude death rate for 10-y age classes (years).Discussion The results of our analysis are consistent with previous findings on early-onset pancreatic cancer,[3] showing that the mortality rate for pancreatic cancer, in contrast to other malignancies (eg, lung, breast, and colorectal cancers), has increased rather than decreasing in the US over the past 20 years, and that this surge has occurred primarily in the male sex and in the older population (ie, individuals aged 55 years or older), with a notable peak in 2021, when the highest number of COVID-19 cases were diagnosed in the US, thus exacerbating shortcomings in care access and curative surgery.[6] This 20-year unfavorable trend can be attributed to several factors, including the aging of the population, the continued influence of risk factors for this type of malignancy (smoking and alcohol consumption, physical inactivity, unhealthy diet, obesity), and the lack of significant advances in treatment.[2,3] Although the study of pancreatic cancer mortality in the general population has important epidemiologic implications, the results could be actually confounded by a number of factors. In particular, given that the incidence of pancreatic cancer is also increased, part of pancreatic cancer-related mortality may be also due to the increased incidence, as the survival rate for this type of malignancy has not improved significantly.[7] To this end, the recent publication of a phase I trial based on the administration of mRNA neoantigen vaccines highlights interesting scenarios, as the use of this innovative therapeutic approach was associated with significantly longer relapse-free survival in responders compared to those undergoing standard treatment,[8] raising hopes that pancreatic cancer mortality could ultimately be reduced in the coming years. Acknowledgments None. Author contributions CM was involved in conceptualization, methodology, validation, and writing. GL was involved in conceptualization, data curation and analysis, and original draft preparation. Financial support None. Conflicts of interest The authors declare no conflicts of interest. Ethics approval This article does not contain any experiments with humans. CDC WONDER is a fully anonymized and publicly available database, so ethics committee approval was not required for this study.