Rising early-onset cancer diagnoses in the US appear to be driven by increased detection, not disease

Harvard Medical School, Brigham and Women’s Hospital, and Dell Medical School researchers report that rising rates of early-onset cancer in the United States may reflect more diagnoses rather than more disease.

Cancer awareness and prevention have intensified over many decades, removing potential environmental risk factors from daily life. Mortality of all cancers combined in adults under 50 has decreased by nearly half since the 1990s.

Still, public concern has climbed amidst rising diagnoses and high-profile early-onset cases. PubMed citations related to early-onset cancer more than tripled and screening ages have been shifted down to 45 for colorectal cancer and 40 for breast cancer. Uncertainty persists about whether the higher case counts signal greater cancer occurrence or more frequent detection.

In the study, “The Rise in Early-Onset Cancer in the US Population—More Apparent Than Real,” published in JAMA Internal Medicine, investigators analyzed trends in cancer incidence and mortality to assess whether rising diagnoses in adults younger than 50 years reflected clinically meaningful disease.

Data covered eight cancers with the fastest-rising incidence since 1992: thyroid, anal, kidney, small intestine, colorectal, endometrial, pancreas, and myeloma. Together, these doubled in incidence, while mortality remained unchanged at 5.9 deaths per 100,000 from 1992 to 2022.

Researchers drew on population-based incidence data from the Surveillance, Epidemiology, and End Results program and mortality data from the National Vital Statistics System. They examined aggregate and site-specific trends, applied three-year moving averages, and analyzed metastatic-at-diagnosis incidence.

Colorectal mortality rose slightly while incidence rose faster. Neuroendocrine tumors and reclassified appendiceal cancers may partly explain higher diagnostic counts. For endometrial cancer, incidence and mortality rose in parallel with increasing obesity rates and fewer hysterectomies, contributing to rising risk.

Thyroid and kidney cancers displayed sharp incidence increases alongside stable or declining mortality, patterns consistent with overdiagnosis through imaging and lower diagnostic thresholds.

Pancreatic, small intestine, and myeloma similarly showed rising incidence without mortality increases, consistent with incidental detection and earlier diagnosis. Anal cancer incidence rose then declined, likely reflecting HPV/HIV epidemiology while mortality remained stable.

Breast cancer, although not among the fastest-rising by relative increase, accounted for one of the largest absolute increases in early-onset diagnoses, exceeding 100,000 additional cases since 1992. Mortality in breast cancer fell by half, reflecting improvements in systemic therapy. Excess diagnoses largely reflected early-stage disease identified through increased screening.

Authors conclude that the seemingly epidemic of early-onset cancers appears to be driven more by an increase in diagnosis than by an actual surge in life-threatening disease.

While some increases in clinically meaningful cancers exist, they are small and site-specific. The authors caution that interpreting incidence trends as proof of an epidemic may prompt unnecessary screening, overdiagnosis and treatment while diverting attention and resources from more pressing health threats to young adults, including rising deaths from suicide and unintentional injuries.

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