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Increase in Young-Onset Pancreatic Cancer May Be Due to Overdiagnosis of Early-Stage Endocrine Cancer


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A recent analysis of pancreatic cancer data in young adults (aged 15–39) has found that although there is an increase in incidence, the mortality rate remains stable. According to Patel et al, who published their findings in the Annals of Internal Medicine, the rise in incidence is primarily due to an increase in the detection of smaller, early-stage endocrine cancer, and not an increase in pancreatic adenocarcinoma. The investigators explained that their findings reflect the detection of previously undetected disease, rather than a true increase in cancer occurrence.

Globally, pancreatic cancer has become the third leading cause of cancer-related deaths, and the incidence of the disease is on the rise. The vast majority of pancreatic cancers—more than 95%—are pancreatic ductal adenocarcinoma, and previous studies have shown that in younger adults, the incidence of pancreatic ductal adenocarcinoma has increased in younger women but remained stable in men.

Study Methodology

The researchers obtained data on pancreatic cancer incidence, histology, and stage distribution for young adults (aged 15–39) from the U.S. Cancer Statistics for 2001 to 2019. Pancreatic cancer mortality for the same time frame was obtained from the National Vital Statistics System. They used the International Classification of Diseases for Oncology, 3rd Edition, to define four histologic categories: adenocarcinoma, endocrine, solid pseudopapillary, and other.

The Joinpoint Regression Program 5.2.0 was used to compute average annual percent change (AAPC) and 95% confidence intervals (CIs).

Key Results

The researchers found that the incidence of pancreatic cancer increased 2.1-fold in young women—from 3.3 (95% CI = 2.8–3.8) to 6.9 (95% CI = 6.2–7.6) per million; AAPC = 4.8% (95% CI = 4.1%–5.6%)—and 1.6-fold in young men—from 3.9 (95% CI = 3.3–4.4) to 6.2 (95% CI = 5.6–6.9) per million; AAPC = 2.7% (95% CI = 2.0%–3.5%). Of note, the rate of cancer-directed pancreatic surgery more than doubled in women (approximately 1.5–4.7 per million) and men (approximately 1.1–2.3 per million), indicating a substantial increase in surgical interventions in response to the increasing incidence. Nonetheless, death from pancreatic cancer was stable in both sexes (approximately 1.5 and 2.5 deaths per million for women and men, respectively).

In addition, their analysis showed that most of the increase in incidence was attributable to early-stage cancer, which increased from 0.6 (95% CI = 0.4–0.9) to 3.7 (CI = 3.2–4.3) per million women (AAPC = 11.7%; 95% CI = 10.4%–13.6%) and from 0.4 (95% CI = 0.2–0.6) to 2.2 (95% CI = 1.8–2.6) per million men (AAPC = 11.1%; 95% CI = 9.7%–13.1%). Consistent with this finding, the incidence of small tumors (≤ 2 cm) increased eightfold in women (approximately 0.22–1.8 per million) and threefold in men (approximately 0.33–1 per million). There was no statistically significant change in the incidence of late-stage cancer in women or men (P > .20 for AAPC).

KEY POINTS

  • The rise in incidence of pancreatic cancer among younger adults is primarily due to the increased detection of smaller, early-stage pancreatic cancer, and not an increase in pancreatic adenocarcinoma.
  • Stable mortality in younger adults suggests that the increase in early-onset pancreatic cancer reflects the detection of previously undetected disease rather than a true increase in cancer occurrence.

The researchers found that the increase in incidence was not attributable to adenocarcinoma. When the stage-specific analysis was restricted to adenocarcinoma alone, early- and late-stage disease were stable in both women and men.

Instead, most of the increase was attributable to endocrine cancer and solid pseudopapillary neoplasms. Among women, the incidence of endocrine cancer increased from 0.9 (95% CI = 0.7–1.3) to 2.8 (95% CI = 2.4–3.3) per million (AAPC = 7.3%; 95% CI = 5.3%–11.0%), and among men, that incidence increased from 0.6 (95% CI = 0.4–0.9) to 2.8 (95% CI = 2.3–3.3) per million (AAPC = 7.5%; 95% CI = 6.5%–9.0%). Among women, the incidence of solid pseudopapillary neoplasms increased from 0.1 to 2 (95% CI = 1.6–2.4) per million (AAPC = 14.4%; 95% CI = 12.3%–18.3%). There was no statistically significant change in the incidence of other subtypes (P > .20 for AAPCs).

“The increasing incidence of pancreatic cancer in younger Americans is primarily due to increased detection of smaller, early-stage endocrine cancer—not an increase in pancreatic adenocarcinoma. The backdrop of stable mortality suggests that the recent increase in early-onset pancreatic cancer reflects detection of previously undetected disease rather than a true increase in cancer occurrence,” concluded the study authors.

Gilbert Welch, MD, MPH, of the Center for Surgery and Public Health, Brigham and Women’s Hospital, is the corresponding author of this study.

Disclosure: For full disclosures of the study authors, visit acpjournals.org/journal/aim.


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