Growing burden of early-onset pancreatic cancer without increasing risk: what is the trick

Abstract

The rise in early-onset cancers, including pancreatic cancer, has attracted major attention from the media, clinicians, and researchers. This growing cancer burden is largely driven by population growth and ageing rather than by an increase in risk, estimated by age-adjusted incidence. Distinguishing between cancer burden and risk is essential to avoid misinterpretation and unwarranted alarm, as each carries distinct implications for public health interventions.

The burden of early-onset pancreatic cancer

The burden of early-onset cancers, defined as cancer diagnosed before the age of 50, is growing globally, attracting major public, media, public health authorities, and researchers attention^1,2. Based on the Global Burden of Disease (GBD) data, Tan et al. concluded that “the disease burden of early-onset pancreatic cancer is increasing worldwide, highlighting the need for effective interventions.”³ Amidst the confusion surrounding trends in early-onset cancers, we challenge Tan et al.’s emphasis on the rise of early-onset pancreatic cancer and its genuine implications. The authors main takeaway is “the global burden of early-onset pancreatic cancer has increased over the past three decades, with notable variances between regions and countries”³. Based on the trends in the number of cases, this statement is true, the burden is indeed increasing. However, the study also shows a stable age-standardized prevalence rate, with 1.04 cases per 100,000 in 1990 compared to 1.03 per 100,000 in 2021. How can the burden of pancreatic cancer increase while the age-standardized prevalence stays stable? Let’s break it down.

The role of population growth and ageing

First, due to the worldwide growth of the population, the burden, that is, the number of cancer cases—of early- as well as later-onset cancers—is growing^4,5. Second, because the risk of pancreatic cancer increases with age, the aging of the population is the other major cause of the increase in the number of cases^4–6. As raised by Tan et al., this underscores the need to apply age standardization when analyzing cancer trends over time, thereby accounting for population growth and ageing. Without such standardization, cancer trends reflect essentially demographic changes. Hence, in a recent paper from Zhao et al. assessing worldwide trends of early-onset cancers across all cancer sites, a relative increase of 79% in the number of early-onset cancer cases was reported for the period between 1990 and 2019⁷. Interestingly, the marginal relative increase of 5% in the age-standardized estimates was not reported as a main result, and, consequently, the effects of population growth and aging were overlooked. Emphasizing absolute numbers rather than age-standardized estimates may contribute to misunderstanding the information conveyed by each of these statistics.

Be wary of prevalence measures

Third, another point is the use of prevalence rather than incidence to assess cancer trends. Indeed, age-standardized incidence rates, defined as the number of new cases occurring in a population at risk within a specific period of time, are key metrics in cancer analytical epidemiology, and are typically reported when studying cancer trends^8,9. Therefore, the reporting of age-standardized prevalence rates by Tan et al. should have been complemented with age-standardized incidence rates to provide a more comprehensive description of early-onset pancreatic cancer trends³. As prevalence rates reflect the current number of cases in a given time in a population, they are influenced by survival and disease duration^8,10,11. When survival rates improve, for example, due to better treatments or earlier diagnosis, people live longer with a cancer diagnosis. This extended survival results in a greater number of individuals alive with a cancer diagnosis, leading to a rise in prevalence, although there might be no increase in the incidence rate of new cases⁸. Thus, a rise in prevalence can reveal a positive public health trend. Prevalence rates also mirror mortality rates, and Tan et al. noted a substantial decrease in age-standardized mortality rate of early-onset pancreatic cancer from 0.75 to 0.65 deaths per 100,000, that is, a 13% relative reduction, between 1990 and 2021³.

Early-onset pancreatic cancer burden versus risk

While caution is warranted to prevent overstated concern about pancreatic cancer trends before the age of 50, one should highlight that trends might differ substantially, e.g., among individuals in their twenties compared to those in their forties, and from one country to the other¹². For instance, between 1993 and 2019, in the United Kingdom, the relative increase was 281% among people aged 0 to 24 years compared to 23% among people aged 25 to 49 years old¹³. Further, the high lethality of the disease at all ages calls for individual risk-based evaluation to guide screening, and for early identification of clinical signs and symptoms to guide diagnosis processes^14,15. Our point here is to highlight the differences in the population-level information provided, on the one hand, by changes in the cancer burden and, on the other hand, by changes in the cancer risk. The burden, that is, the number of prevalent or new cases, informs healthcare needs and planning and resource allocation in health systems. The risk, that is, the age-standardized incidence, informs us about the probability of getting cancer at a given age and is useful to identify potential etiological factors; if the risk is not increasing, there is no reason to search for emerging causes or call for strengthening prevention, or at least no more than usual. Of note, the risk of cancer depends not only on exposure to carcinogenic factors but also on detection practices and classification criteria, meaning that changes in carcinogenic exposure alone may not fully explain changes in age-standardized incidence over time.

Interpreting the growing burden in context

In conclusion, by stating that “[…] the global number of prevalent cases and deaths increased dramatically between 1990 and 2021”, Tan et al. may create a sense of alarm, resulting in calls for etiological inquiries and urgent risk reduction interventions. While the growing burden of pancreatic cancer puts healthcare systems under pressure globally, we should be wary of the confusion between burden and risk, and the different implications they have in terms of public health interventions. Eventually, we should also acknowledge our substantial progress in fighting early-onset pancreatic cancer, highlighted by the downward trend in mortality rate.

Author contributions

A.B. wrote the manuscript. A.C. provided support and editing. Both authors agreed on the final version.

Data availability

No datasets were generated or analyzed during the current study.

Competing interests

The authors declare no competing interests.