ASCO Sessions Explore Data and Dynamics of Early-Onset Cancer

For several years, rising rates of cancer among adults younger than age 50 have alarmed scientists and policy makers.¹ What’s causing this uptick, especially in colorectal, pancreatic, kidney, breast, and uterine cancers?

Early-onset cancer occurs when cancer normally seen in older adults is diagnosed in those between 18 and 49 years. Its rise was an undercurrent of the annual meeting of the American Society of Clinical Oncology (ASCO), which featured important new data, highlighted a national research agenda, and provided insights from top trials.

The list of potential triggers for early-onset cancer is long. Obesity is clearly a cause, as is increased inflammation, possibly aggravated by the COVID-19 pandemic. Yet, there’s agreement that no single factor is driving the increase. Genetics, stress, and other environmental factors have been cited, and a 2024 study presented at the American Association of Cancer Research annual meeting suggested that a milieu of factors are accelerating aging, causing more cancer.

Yelena Y. Jenjigian, MD | Image credit: MSKCC

Yelena Y. Jenjigian, MD, of Memorial Sloan Kettering, highlighted the trend in a press conference where she shared results for MATTERHORN, presented during the plenary session.² The phase 3 trial found that adding perioperative durvalumab to the standard chemotherapy combination boosted survival for those with gastric or gastroesophageal junction (GEJ) cancer.

Among this population, she said, “1.2 million people will die of this disease in 2025, and there's an increase in incidence in patients under age 50.”

Although gastric cancer is historically a disease of older patients—the average age at diagnosis is 68 years—those in their 40s and 50s are at increased risk,³ and Jenjigian saw this in MATTERHORN, with participants ranging from 26 to 85 years of age.

“This used to be a disease of men in their 70s, and now we're seeing a younger, more diverse patient population—a lot of Hispanic women with diffuse gastric cancer,” she said in response to a question from The American Journal of Managed Care^®. Young patients are typically more willing to enroll in clinical trials, and this was borne out in the US cohort in MATTERHORN; Jenjigian said patients were typically in their 40s or 50s, and roughly a third were younger than age 50.

Not yet 50 herself, Jenjigian noted, “I’m sorry to say I have patients who are younger than me in my clinic routinely.”

Real-World Data in Colorectal Cancer

Gastric cancer is emblematic of the rise of gastrointestinal (GI) and genitourinary (GU) cancers among young adults,⁴ which suggests lifestyle- or environmental-related triggers. Colorectal cancer (CRC), which includes cancer of the large intestine to the rectum, is perhaps the poster child for the trend.

Former National Cancer Institute (NCI) Director Kimryn Rathmell, MD, PhD, MMHC, now head of the Ohio State University Comprehensive Cancer Center, said during Monday's ASCO session on early onset cancer that in the 1990s, CRC was the fourth leading cause of cancer death of adults under age 50; now CRC is the leading cause of cancer death in young men and second among young women.⁵

“We’ve all seen shockingly young patients in our clinics,” she said.

A report by Yale School of Medicine noted that while advanced-stage CRC rose 8% overall from the mid-2000s to 2019, diagnoses of those under age 55 rose from 11% of cases in 1995 to 20% in 2019. And a study published in The Lancet in 2024 identified 14 countries, including the United States, where early-onset CRC is on the rise.⁶

What do we know about these patients?

Jessica Paulus, ScD | Image credit: McKesson

Jessica Paulus, ScD, senior director of observational research at Ontada, offered answers during a presentation May 30 that analyzed real-world data from 104,281 patients with CRC both inside and outside The US Oncology Network. Results showed that patients diagnosed below age 50 with CRC were more likely to be a member of a minority group, live in an urban area, and be under stress, based on their answers to a validated test.

Patient characteristics were pulled from the oncology-specific electronic health record, iKnowMed, for those treated between 2000 and 2024.⁷ Other results showed:

• Age. 14,611 (14%) had early-onset disease (EO-CRC), with a median age of 44 years; 89,670 (86%) had average-onset cancer (AO-CRC), with a median age of 67 years.
• Race/ethnicity. Compared with the AO-CRC group, those in the EO-CRC group were more likely to be Black (11% vs 8%), American Indian or Alaska Native (1.3% vs 0.9%), or Hispanic (11% vs 8%). Overall, 20% of patients in the EO-CRC group were a race other than White, compared with 15% with AO-CRC.
• Obesity. 36% of the EO-CRC group was obese, compared with 31% in the AO-CRC group. This aligns with higher obesity prevalence among younger Americans: data from the CDC show that patients between ages 40 and 59 have a higher prevalence of obesity (44.1%) than those aged 20 to 39 years (39.8%) and those aged 60 years or older (41.5%).
• Environment. Patients with EO-CRC were more likely to live in urban areas (69%) vs 63% for AO-CRC patients.
• Stress. Investigators evaluated patients’ scores on the National Comprehensive Cancer Network Distress Thermometer; they found that EO-CRC patients were more likely to report high distress (29% vs 22%), with a smaller share reporting low distress (71% vs 78%).
• Mortality. Younger patients had higher overall survival (OS) rates than older patients. The 5-year OS probability was 72% in EO-CRC but 64% for AO-CRC.

In her presentation and in an interview, Paulus highlighted the fact that the average age of EO-CRC patients is a year younger than the current recommended age to start CRC screening, which was dropped from 50 to 45 in 2021.⁸ This has consequences, both for patients and the health system, as cancer in younger adults may not be caught until later stages, when it costs more treat.

“We…observed a marked difference in stage diagnosis among the early-onset patients versus the average-onset patients,” Paulus explained during the session, noting that “34% of the early-onset patients are diagnosed at Stage IV, versus 28% of the average-onset patients. We see a similar pattern for Stage III at diagnosis.

“Taken together, this corresponds to a nearly 10 percentage point difference in the burden of advanced stage at diagnosis between the 2 age groups,” she said.

Should the US Preventive Services Task Force drop the age further?

“The question of whether to drop it is really an empirical one,” Paulus said in the interview. “It's a cost-benefit analysis.” Screening everyone would be costly, she said, and a traditional colonoscopy is not a pleasant patient experience, although there are now less invasive alternatives.

“Overall, early-onset colorectal cancer is still rare,” Paulus continued. “The better opportunity is what we've done in lung cancer,” in which guidelines limit screening to those who meet high-risk criteria.

The challenge with developing a screening algorithm for CRC, Paulus explained, is that while smoking is clearly the most critical risk factor in lung cancer, CRC has many more causes. “There’s not a smoking gun, she said.

Research Into Cancer Drivers

Monday’s panel, “Beyond the Headlines: The Real Impact of Early Onset Cancers,” focused more on current clinical research and policy shifts needed to address the needs of growing numbers of young adults with cancer.

LeeAnn Bailey, PhD | Image credit: LinkedIn

LeeAnn Bailey, PhD, who is branch chief of Integrated Networks Branch at the NCI's Center to Reduce Cancer Health Disparities, highlighted work by the agency’s early-onset initiative, which seeks to speed the understanding of what is driving the increase in the context of patient experience and survivorship.

The rise of early cancers is a global phenomenon, she said. “Early-onset cancer has increased by 79.1% between 1990 and 2019, and the number of early onset cancer deaths increased by 27.7% between 1990 and 2019,” Bailey said, who said increases in early onset cancer will continue through 2030.

“It’s important to acknowledge that early-onset cancer is wide-reaching, and it really does affect everyone from all different walks of life,” she said.

Bailey reviewed a major NCI analysis, led by Meredith Shiels, PhD, MHS, that appeared recently in Cancer Discovery, an AACR journal.⁹ The paper identified 14 cancers that had increased in at least 1 early-onset age group; the groups were specified as 15 to 29 years, 30 to 39 years, and 40 to 49 years. These included female breast, colorectal, kidney, testicular, uterine and pancreatic cancers, as well as lymphoid neoplasms. Nine of these cancers also increased in at least 1 group of patients between 50 and 79 years of age.

“Although there were not concomitant increases in mortality rates for most cancers, colorectal, uterine, and testicular cancer mortality rates increased in early-onset age groups,” the authors wrote. “The drivers of increasing incidence rates are cancer-specific and could include a combination of established and perhaps new etiologic factors, and increased detection.”

Andrew T. Chan, MD, MPH | Image credit: Mass General Brigham

Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, also focused on CRC as a window into the phenomenon. “This tumor type is perhaps the earliest tumor in which we really started to notice this very troubling trend among young adults,” he said.

CRC also exemplifies the challenges of understanding early-onset cancer, as it can be affected by genetic factors, notably Lynch syndrome, as well as lifestyle and changes in the environment. Chan's focus is on the 85% of patients with early-onset colorectal cancers that involve “no family history or genetic predisposition.”

Genome-wide association studies have identified some patterns, “but these are really incomplete explanations to what we are seeing.”

Chan outlined a host of research initiatives, both at Harvard and at other institutions, that have teased out contributors to rising rates of early-onset CRC:

• Poor diet quality, including an increase ultra processed foods, which also contributes to obesity
• Changes to the gut microbiome
• Increased use of oral antibiotics
• Increased alcohol use, particularly binge drinking and patterns of drinking alcohol without eating

Although this work has identified several important risk factors, the known triggers cannot account for all the early-onset cancer doctors are seeing, Chan said. “We need to work to identify new risk factors,” he said. “We all have examples of patients in our clinics who have colorectal cancer but have no identifiable colorectal cancer risk factors.”

What’s needed is a large-scale epidemiological project to estimate the share of early-onset cancers attributable to known risk factors, so that scientists can identify gaps and, ultimately, the exposures causing the balance of the cancers, Chan said.

Three areas of research will be critical: building better epidemiology cohorts, increasing molecular analysis of cancer specimens, and developing models that can identify cause and effect in CRC.

Data gaps exist, Chan said, but there are also opportunities to fill in these gaps. There are thousands of proteins in the blood that remain unexplored as potential contaminants that could drive cancer. There’s work in epigenetics to understand the effects of repeated exposure to inflammation—and what this does to stem cells that could promote future tumor growth.

“This is something that can be applied to early-onset cancer specimens to allow us to understand what exposures early in life could be leading to later-life cancers,” Chan said.

Developing precision trials that can identify which early exposures are causing cancer is the next step, he said, because unlocking the cause of early-onset cancer is key to the next step. Applying knowledge gained in pursuing the roots of early-onset CRC can then bring insights into other cancers, “so you can really understand more about this troubling trend across different tumors.”

References

1. Generation X and millennials in US have higher risk of developing 17 cancers compared to older generations, new study suggests. News release. American Cancer Society. July 31, 2024. Accessed June 5, 2025. https://pressroom.cancer.org/higherriskGenXandMillennials

2. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer. N Engl J Med. Published online June 1, 2025. doi:10.1056/NEJMoa2503701

3. Harringa A. Many younger patients with stomach cancer have a distinct disease, Mayo research discovers. Mayo Clinic. December 17, 2019. Accessed June 4, 2025. https://newsnetwork.mayoclinic.org/discussion/many-younger-patients-with-stomach-cancer-have-a-distinct-disease-mayo-research-discovers

4. Piersol B. The latest research on why so many young adults are getting cancer. Memorial Sloan Kettering Cancer Center. January 16, 2025. Accessed June 5, 2025. https://www.mskcc.org/news/why-is-cancer-rising-among-young-adults

5. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. Published online January 17, 2024. doi:10.3322/caac.2182

6. Sung H, Siegel RL, Laversanne M, et al. Colorectal cancer incidence trends in younger versus older adults: an analysis of population-based cancer registry data. Lancet Oncol. 2025;26(1):51-63. doi:10.1016/S1470-2045(24)00600-4

7. Herms L, Pasha S, Guo J, Conkling PR, Paulus J. Real-world social determinants of health (SDOH) and outcomes of early-onset colorectal cancer (EO-CRC): An analysis of a large, nationally representative US community oncology network. J Clin Oncol. 2025;43(suppl 16):Abstract 11005. doi:10.1200/JCO.2025.43.16_suppl.11005

8. US Preventive Services Task Force; Davidson KW, Barry MJ, Mangione CM, et al. Screening for colorectal cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;325(19):1965-1977. doi:10.1001/jama.2021.6238.

9. Shiels MS, Haque AT, de Gonzalez AB, et al. Trends in cancer incidence and mortality rates in early-onset and older-onset age groups in the United States, 2010–2019. Cancer Discov OF1–OF14. doi:10.1158/2159-8290.CD-24-1678