Looking at trends in early-onset cancer

For decades, cancer has been considered a disease that primarily affects those ages 50 years and older, but some research shows incidence rates slowly creeping up in younger patients. This prompts questions about what's behind the numbers and how physicians can best address it with their patients.

From 2000 to 2019, the incidence of 17 types of cancer rose among younger birth cohorts, a study published by the Lancet Public Health in August found. Of those 17, nine rose despite declining in older populations. Additional data published by CA: A Cancer Journal for Clinicians in January showed that between 1995 and 2020, people younger than age 50 years were the only one of three age groups studied to experience an increase in overall cancer incidence.

Currently, early-onset cancer, typically defined as cancer diagnosed between ages 18 and 49 years, make up around 8% to 10% of the total cancer population, explained Veda Giri, MD, a medical oncologist at Yale Medicine and director of Yale Cancer Center's Early-Onset Cancer Program at Smilow Cancer Hospital in New Haven, Conn. And although incidence has been increasing across types, “in general, the two cancers with the greatest increases … are colorectal cancer and breast cancer. Even within those two, it looks like the GI cancers are the most rapidly rising in terms of incidence,” Dr. Giri said.

A look at the numbers

Colorectal cancer (CRC) is one of the nine types of cancer identified in the Lancet Public Health study where incidence increased for younger cohorts and simultaneously declined in older cohorts.

Timothy J. Wilt, MD, MPH, MACP, put those numbers into context given debate about appropriate ages to start CRC screening. “For adults ages 45 to 49, the rates (annual incidence) of CRC are very low and have changed little since 2000,” explained Dr. Wilt, a professor of medicine and public health at the University of Minnesota and a core investigator at the Minneapolis VA Center for Care Delivery and Outcomes Research.

From 2000 to 2021, CRC incidence rose slightly in individuals 45 to 49 years (28.9 to 40.2 per 100,000), Surveillance, Epidemiology, and End Results (SEER) registry data show. In the same time frame, incidence decreased in those ages 50 to 64 years (85.1 to 71.9 per 100,000) and in persons ages 65 years or older (305.3 to 151.7 per 100,000), with the declines likely attributable to screening.

For breast cancer, SEER registry data show that incidence rates were 119.9 per 100,000 in 2000 versus 141.9 per 100,000 in 2021 among women 40 to 44 years and 194.9 per 100,000 versus 209.7 per 100,000, respectively, for those ages 45 to 49 years. Incidence rates in the same time frame were 307.1 versus 284.3 per 100,000 for those ages 50 to 64 years and 442.2 versus 445.6 per 100,000 for those ages 65 years and older.

Of note, incidence rates do not differentiate between patients who are at high and average risk of cancer. Breast cancer is still fairly uncommon in women in their 40s, Dr. Wilt said, and when it comes to translating increased rates into actual patient impact, it's best to focus on absolute numbers as opposed to relative risk differences. “These rates and absolute differences remain very small for individuals younger than age 50,” he stressed.

Unclear causes

What's driving these upticks remains a question.

Experts hypothesize that a wide range of environmental factors may be contributing and that the cause is likely multifactorial. Changes in diet, the proliferation of ultra-processed food, a more sedentary lifestyle, and exposure to plastics and other potential hazards may all play a role, along with improved screening technology (e.g., more sensitive mammography and better scopes for CRC detection). Notably, 10 of the 17 types of cancer that rose in young adults are associated with obesity, including colon and rectal cancer and estrogen receptor-positive breast cancer, the Lancet Public Health study found. In 1950, the U.S. obesity rate was just 7%. It now sits at around 42%, according to the CDC.

Alcohol is another likely culprit. The latest Cancer Progress Report from the American Association for Cancer Research calls for increased awareness about the link between alcohol and the disease via public messaging campaigns and warning labels on packaging. In addition, the World Health Organization published a statement in the Lancet Public Health in 2023 on the health and cancer risks related to even low levels of alcohol consumption.

Because asymptomatic early-onset cancer patients may be too young to fall under general population-level screening guidelines, “these individuals may present with a cancer diagnosis at a later stage and therefore have worse clinical outcomes,” said Dr. Giri. Dr. Wilt added that more individuals in their 40s are now undergoing screening, “which likely contributes to the small absolute increase in newly diagnosed cancers in this age group.”

Younger patients who do have symptoms, and their clinicians, might dismiss them, potentially prolonging the time to diagnosis. A systematic review and meta-analysis published in JAMA Network Open in May found that nearly half of patients diagnosed with early-onset CRC presented with hematochezia and abdominal pain and one-quarter with altered bowel habits, and that diagnosis delays of four to six months were common. The researchers were unable to evaluate the impact of time to diagnosis on CRC outcomes but noted “it is well established that risk for progression to more advanced-stage disease increases over time.”

“If a 65-year-old goes to their doctor and talks about blood in the stool, they're more likely to be referred immediately to colonoscopy, as opposed to a 30-year-old, where they may be, for example, discounted and [be told], ‘Oh, it's hemorrhoids,’” said Scott Kopetz, MD, PhD, FACP, a professor of gastrointestinal medical oncology at MD Anderson Cancer Center at the University of Texas in Houston, who was not involved in the study.

Guidance on screening

The data on increases in early-onset cancer have led to some changes in screening guidelines at the federal level. In 2021, the U.S. Preventive Services Task Force (USPSTF) issued an updated statement that continued to recommend CRC screening in asymptomatic average-risk adults ages 50 to 75 years (grade A recommendation) but also recommended offering screening starting at age 45 years (grade B recommendation). “That's a message that has gotten out, but not as much as we'd like,” said Dr. Kopetz.

The Task Force also issued a grade B recommendation earlier this year that asymptomatic average-risk women should receive biennial mammography for breast cancer screening starting at age 40 years instead of age 50 years.

ACP's most recent guidance statement on breast cancer screening in asymptomatic average-risk women, published in 2019, states that physicians should discuss whether to screen with those ages 40 to 49 years, considering patient preferences and potential benefits and harms, and should offer biennial mammography to those ages 50 to 74 years.

While that guidance predates the current USPSTF recommendation, Dr. Wilt noted that the Canadian Task Force on Preventive Health Care Services issued a draft recommendation statement in May “suggesting clinicians not routinely screen women ages 40 to 49 based on evidence from randomized trials, observational and modeling studies, and patient preferences and values” and stating that breast cancer screening is a personal choice.

For CRC, an ACP guidance statement published in 2023 says that clinicians should start screening in asymptomatic average-risk adults at age 50 years and should consider not screening asymptomatic average-risk adults between the ages of 45 to 49 years.

ACP guidance statements prioritize evidence from randomized controlled trials over statistical modeling, Dr. Wilt said. They are also formulated to clarify conflicting information from existing guidelines and take additional factors like patients' values and preferences, cost, equity, and disparities into account.

“More screening, including starting at an earlier age, does not always lead to better health for individuals or the population” and could exacerbate health care disparities, said Dr. Wilt, who is a former member and Chair of ACP's Clinical Guidelines Committee and a coauthor on both ACP guidance statements. “A more equitable approach would be to use resources in priority populations where evidence more convincingly supports net benefit.”

Potential harms of screening include overdiagnosis and false-positive tests that lead to additional, unnecessary, and invasive testing, fear, anxiety, and resource use, to name a few.

In the case of breast cancer, Otis Brawley, MD, MACP, an oncologist and epidemiologist at Johns Hopkins University in Baltimore, pointed out that if a woman is screened every year from age 40 to age 75, that equals 35 doses of radiation, not counting any additional radiation from subsequent testing when a mammogram is read as abnormal, something that's much more common in women in their 40s than in their 50s.

At Johns Hopkins, Dr. Brawley's seen instances where women who start getting mammograms in their 40s stop before their 50s due to bad experiences with abnormal results, anxiety, and additional testing. “In other words, they stop getting mammograms just at the time where we have 12 studies to show it's beneficial,” he said.

Talking to patients

Discussing the rise in early-onset cancer with patients requires walking a fine line between increasing education and fearmongering, said Andrea Cercek, MD, a gastrointestinal medical oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancers at Memorial Sloan Kettering Cancer Center in New York City.

If younger patients bring up concerns, Dr. Wilt recommends explaining the data in terms of absolute differences and laying out harms associated with beginning routine screening earlier.

“If after that they say, ‘You know, I've heard this, [but] I'd like to get screened, thanks,’ I'd order the test. I'd figure out the right test for them,” he said.

While screening guidelines are intended for asymptomatic, average-risk patients, younger patients who are at high risk of cancer or have symptoms need screening and diagnosis, respectively.

To determine individuals' cancer risk, primary care physicians need to take thorough family histories, experts said. This will not only help determine if and when patients should begin earlier screening for specific types of cancer but will also help physicians determine if genetic testing is necessary for conditions like Lynch syndrome, for example.

“When we talk about family history, it's thinking about cancers in blood relatives on both sides of the family,” Dr. Giri said. Physicians should also think broadly about cancer types and not just ask about breast cancer in female relatives or prostate cancer in male relatives, because ultimately those cancers “could be connected by a common genetic source,” she said. (For more information on BRCA1 and BRCA2 mutations specifically, see the related article.)

When patients present with symptoms, an appropriate workup is crucial. “We need to pay attention to symptoms, and particularly persistent symptoms,” said Dr. Cercek. “My advice would be just to take symptoms seriously and not dismiss them just because someone is in their 30s.”

Dr. Kopetz agreed. Ideally, there should be “really low thresholds for [workup in] patients that are presenting with worrying symptoms at a younger age,” he said.

As always, experts stressed, physicians should continue to promote well-established factors to prevent cancer, including communicating that alcohol is a toxic group 1 carcinogen and promoting not smoking, maintaining a healthy weight, exercising, eating a diet high in vegetables, fruits, lean meats and proteins, and wearing sun protection.

“Too often we're asked what to do once the problem is here and not enough to focus on trying to prevent the problem,” said Dr. Brawley. “Risk reduction or prevention is much more effective than finding the tumor earlier and treating.”