What If Early Cancer Rise Isn't What It Seems?

The widely reported epidemic of early-onset cancer in the United States may be driven largely by increased diagnostic scrutiny rather than a true rise in clinically meaningful disease.

In a comprehensive analysis published in JAMA Internal Medicine, investigators examined trends in the 8 cancer types with the fastest-rising early-onset incidence rates—those increasing more than 1% annually since 1992—and found that while diagnoses had approximately doubled, mortality rates remained stable. The aggregate mortality rate for these cancers was identical in 2022 and 1992 at 5.9 deaths per 100,000 patients younger than 50 years.

"[T]hese cancers are being diagnosed more frequently among young adults without a comparable shift in the feared outcome: death," wrote the study authors, led by Vishal R. Patel, MD, MPH, of Harvard Medical School and Brigham and Women's Hospital. "The pattern suggests that, at least in aggregate, the increased incidence of early-onset cancers appears less an increase in the incidence of clinically meaningful cancer and more an increase in detection," they added.

The investigators analyzed data from the Surveillance, Epidemiology, and End Results program and the National Vital Statistics System for thyroid, anal, renal, small intestinal, colorectal, endometrial, pancreatic, and myeloma cancers, as well as the 8 malignancies showing the steepest incidence increases among patients younger than 50 years.

Individual Cancer Patterns Reveal Heterogeneity

When examined individually, just 2 cancer types demonstrated concerning mortality trends. Colorectal cancer mortality increased approximately 0.5% per year since its 2004 nadir, while endometrial cancer showed parallel rises in both mortality and incidence at approximately 2% per year.

For the remaining 6 cancer types, patterns strongly suggested overdiagnosis. "Thyroid cancer diagnoses skyrocketed, despite extremely stable mortality, a classic signature of overdiagnosis, ie, the detection of disease that would never have caused death," the study authors wrote. Overdiagnosis of thyroid cancer is well-documented in the literature.

Renal cancer demonstrated a similar pattern of rapidly increasing diagnoses despite falling mortality, "likely reflecting incidental detection through increased use of abdominal imaging." For gastrointestinal cancers, including those of the small intestine and pancreas, "overdiagnosis likely explains the rising incidence and stable mortality, much of which reflects the incidental detection of small, indolent neuroendocrine tumors on cross-sectional imaging or endoscopy."

Breast Cancer Mortality Declines Despite Rising Incidence

While breast cancer wasn't among the fastest-growing early-onset cancers (increasing 0.6% annually), it remained the most common early-onset malignancy. Although the investigators identified rising diagnoses among women younger than 50 years, mortality rates decreased by approximately 50% over 3 decades, largely reflecting advances in systemic therapy.

"Thus, the excess diagnoses similarly likely reflect the increased screening intensity in younger patients (ie, more mammograms, ultrasonography, and magnetic resonance imaging) than an increase in the occurrence of clinically meaningful breast cancer," the study authors noted.

Federal Response and Policy Implications

The perceived early-onset cancer crisis prompted significant federal investment, with the Cancer Grand Challenges program allocating $25 million to investigate biological causes. The findings also influenced screening guidelines, as the US Preventive Services Task Force lowered recommended screening ages for colorectal and breast cancers to 45 years and 40 years, respectively.

However, the investigators cautioned against overinterpreting incidence trends without mortality context. "Searching for biological causes for rising incidence in cancers without evidence of a rise in clinically meaningful cancer is bound to be unproductive," they wrote.

Overdiagnosis Beyond Age-Related Risk

In an accompanying editor's note, Ilana B. Richman, MD, MHS, of the Yale School of Medicine; and Cary P. Gross, MD, of the Yale School of Medicine, highlighted the study's broader implications for understanding overdiagnosis.

"These observations imply a different conceptualization of overdiagnosis in which some tumors may be nonprogressive, and thus, are likely to remain occult and undetected unless identified incidentally or on screening, even among younger adults," they wrote.

The findings challenged traditional associations of overdiagnosis primarily with older patients. "Overdiagnosis may be substantial among more indolent cancer types such as thyroid and [renal] cancer, and less so for others like colorectal and endometrial cancers, which may be more aggressive," the editor's note authors indicated.

Clinical and Public Health Care Consequences

The investigators emphasized the significant personal and societal costs of unnecessary cancer diagnoses in young adults. "A cancer diagnosis can profoundly disrupt the lives of young adults, turning those who may feel perfectly healthy into lifelong patients," they noted. 

"The physical toll of cancer treatment is heightened in young adults and can include infertility, long-term organ damage, and secondary cancers." Emotional impacts include "the long-term burden of anxiety and depression that comes with being labeled a cancer survivor can ripple through an individual's family and community."

The results of the study revealed that "mortality of all cancers combined in patients younger than 50 years has decreased by nearly half since the 1990s." Cancer-related deaths comprise only 10% of all deaths in this age group, with "suicides and unintentional deaths (such as those from motor vehicle collisions or drug overdoses) outnumber cancer-[related] deaths more than fourfold, and both are rising."

Conclusions

"Overall, the rise in early-onset cancer appears to be less an epidemic of disease and more an epidemic of diagnosis," the study authors underlined. "The lack of a substantial rise in deaths, despite rising incidence, underscores the need to provide context to the early-onset cancer narrative," they suggested.

The investigators warned that misinterpreting rising incidence could have unintended consequences: "It may alarm the public and perpetuate the idea that something in our environment or lifestyle is triggering more cancers, when physicians may simply be detecting more cases that were always present. Worse, it encourages the belief that young, healthy patients could benefit from low-value screening interventions, such as whole-body imaging and multicancer early detection tests."

"While some of the increase in early-onset cancer is likely real, it is small and confined to a few cancer sites. The epidemic narrative not only exaggerates the problem, but it may also exacerbate it. While more testing is often seen as the solution to an epidemic, it can just as easily be the cause," the study authors concluded.

Disclosures can be found in the published JAMA communications.

Source: JAMA Internal Medicine | Special Communication & Editor's Note