The Enigma of Young Adult Cancer

Earlier this year, Princess Kate Middleton announced that she had cancer. The world responded with shock, partly because she’s only 42. Her 75-year-old father-in-law, King Charles, was also diagnosed almost simultaneously. His announcement drew widespread sympathy as well, but nothing like the shock that greeted Kate’s news. “She is so young!” people exclaimed.

Called early-onset, or young, cancer, such cases are described when diagnosis happens in adults between the ages of 18 and 49. This trend is worrying because until now, age has been a top risk factor for cancer. It has garnered a lot of headlines, such as “The rise in cancer among younger people,” (ABC News), “Cancer cases in young people are rising sharply,” (CNN) and “Cancer Is Striking More Young People and Doctors are Alarmed and Baffled” (WSJ).

It’s a real phenomenon.

We do not know yet what type of cancer Kate has, but the rates of more than a dozen malignancies are increasing among adults under the age of 50. Between 1990 and 2019, the global incidence of early-onset cancer increased by 79.1% and the number of early-onset cancer deaths increased by 27.7%. The rates of young cancer vary from country to country, but the global number of incidence and deaths of early-onset cancer is expected to increase by 31% and 21%, respectively, in 2030.

Early-onset breast, tracheal, bronchus and lung, stomach, and colorectal cancers showed the highest mortality and disability adjusted life years in 2019. Globally, early-onset nasopharyngeal and prostate cancer showed the fastest increase. Pancreatic ductal adenocarcinoma, which is expected to become the second leading cause of cancer-related deaths by 2030, is steadily rising among young adults (Ann Surg. Oncol. 2023).

One response has been to advocate for earlier screening, which is already happening in the U.S. for breast cancer. “But in most cases, that is simply not practical. It becomes much too expensive,” said Savio Barreto, PhD, a surgeon and associate professor at the Flinders Medical Centre, Australia.

However, in the commercial realm, this is also regarded as a growing unmet need and thus, an opportunity. There is keen interest in technologies that make screening more practical, cost-effective, and accurate. This has also revealed key questions: what is causing this disturbing trend? And can we curb it?

Colorectal cancer screening steps up

In the late-1990s, colorectal cancer was the fourth-leading cause of cancer death in both men and women younger than 50 in the U.S., but is now first in men and second in women. This dramatic shift has led to calls for wider screening.

Colonoscopies are the gold standard of colon cancer screening. They identify approximately 95% of positive cases and allow gastroenterologists to both detect and remove potentially precancerous colon polyps in one sitting. The procedure is recommended for most people aged 45 or older and at average risk of colon cancer every 10 years.

Unfortunately, a lot of people skip their colonoscopies. The procedure is not even recommended for many young adults. Several companies now have products on the market or close to ready, making it easier to expand colon cancer testing without pushing colonoscopies.

Exact Sciences is one of the pioneers in this field. Launched in 2014, its Cologuard^® test was the first DNA-based colorectal test on the market. The test nets Exact about $480 million every quarter. Stool-based tests such as Cologuard are now part of U.S. guidelines, recommended every 1–2 years for people over 45. In a recent study, Cologuard showed 94% sensitivity and 91% specificity.

Exact sees increased demand further down the line, having designed more widely applicable products such as itsoncoExTra^® test. Once a cancer is diagnosed, it should ideally be quickly screened profiled to decide which targeted therapies may be useful. “Labs will do sequencing and call a variant,” says Rick Baehner, MD, chief medical officer of precision medicine oncology, Exact. “But the highest level is that you know that mutation exists, and that it is on the label for a particular therapy. That’s what we aim to deliver.”

There are several key current and upcoming competitors to Cologuard. Mainz Biomed’s ColoAlert, also a DNA based test, is already approved for use in Europe.

Mainz’s next generation CRC test, currently in development, combines a fecal immunochemical test with proprietary mRNA biomarkers. In July of this year, the company filed for Breakthrough Device Designation from the FDA for the new product.

Mainz pointed out that mRNA biomarkers reflect gene expression levels, providing real-time information about cellular activity, which is particularly useful for understanding disease states or responses to treatment. Furthermore, mRNA levels can change rapidly in response to environmental factors, treatments, or disease progression.

Recent studies report that ColoAlert has 97% sensitivity for colorectal cancer and 82% sensitivity for advanced precancerous lesions. In patients with the latter, 100% of high-grade dysplasia instances were detected “We have found that certain mRNA biomarkers can appear early in disease processes, potentially allowing for earlier detection compared to DNA mutations that may appear later or be static over time,” said Guido Baechler, CEO of Mainz. “We believe that for our use case, in particular to detect advanced adenomas with a comparably high sensitivity rate, that the advantages of mRNA predominate the ones over DNA.”

Other tests are trying to get a piece of this market. Just this spring, the FDA approved ColoSense™, which is Geneoscopy’s noninvasive, multitarget stool RNA test.

Around the same time, an FDA advisory panel recommended approval of Guardant Health’s Shield™ blood test. All of these tests will compete in terms of accuracy, convenience, cost, and willingness of insurers to cover them.

Earlier and more accurate mammography

The U.S. has already taken steps to recommend breast cancer screening for younger women. In April of this year, the U.S. Preventive Services Task Force said regular mammograms should start younger than earlier recommended. While they had previously suggested that women could choose to get screened by the age of 40, they now recommend that women aged 40 to 74 get screened every other year.

“More women in their 40s have been getting breast cancer, with rates increasing about 2% each year, so this recommendation will make a big difference for people across the country,” task force chair Wanda Nicholson, MD, said in a press release.

“By starting to screen all women at age 40, we can save nearly 20% more lives from breast cancer overall. This new approach has even greater potential benefit for Black women, who are much more likely to die of breast cancer.”

But if we are going to do more screening it will need to be more efficient. Can artificial intelligence (AI) come to the rescue? AI may indeed help detect more breast cancers, as shown by a recent study of the ScreenTrustMRI tool that scores mammograms and accurately selects patients who need expensive follow up MRIs.

In another study from the University Medical Center Utrecht, real-time AI assistance increased the efficiency and lowered the cost of sentinel lymph node (SN) analysis for breast cancer. SNs are the first lymph nodes to drain lymphatic flow from the tumor and testing them can be difficult and time-consuming. The team from Utrecht found that assisted pathologists reduced their dependence on the tedious process of immunohistochemistry (IHC).which led to substantive cost savings (~3,000€), significant time reductions, and up to 30% improved sensitivity.

It turns out such analysis is an ideal task for AI. SN slides have to be assessed diligently as macrometastases are pretty easily spotted, but smaller metastases are not and may require IHC. However, IHC is time-consuming, costly, and can have significant implications for patients, as those with an SN containing metastases usually require additional adjuvant treatment on top of traditional treatments.

There also does not seem to be much pushback from the doctors, which is an oft-cited concern. “In general, pathologists were happy to work with AI. It saved them time, they felt confident doing it, and they felt that it made their work more enjoyable,” said Carmen van Dooijeweert, MD, PhD, lead author of the study. “Once they were used to AI, they even disliked the control weeks when they could not use AI-assistance. Since the trial, we use it in daily clinical practice,” she added. What causes higher cancer rates in young people?

The main possible causes scientists point to are well-known genetic risks, like BRCA1 and BRCA2, and the usual suspects of diet and environmental exposure. A growing body of research suggests that a low-fiber and high-sugar diet is particularly risky as well.

But will patients act on this information? A recent survey carried out by the Ohio State University Comprehensive Cancer Center suggests that while most people know that colon cancer can run in families, they are not aware of how factors like drinking, obesity, processed food-dense diets, and sedentary lifestyles can increase risk. The survey reached about 1,000 people aged 18 or older.

What are the main questions left to answer about this concerning new trend? Barreto offers these:

• What are the underlying cause(s) of young-onset cancers?

• What are the biological differences between young-onset and sporadic (> 50 years) cancers?

• Can we identify blood biomarkers of people at risk?

Until these questions are answered, the main solution is going to be more and better screening. But expenses, a lack of screening facilities, and a lack of patient awareness stand in the way.

“No one has yet done a large-scale screening [in colon cancer] with 30-year-olds,” said Baechler. “The prevalence is so low it would be very expensive. And yet, we had one patient who was a 38-year-old pregnant woman found to have stage two colon cancer.”

Malorye Branca is a contributing editor at Inside Precision Medicine and a freelance medical science journalist. She has written hundreds of articles, as well as managed and launched health and science magazines, newsletters, and market research report businesses. She has also co-authored two books: Moneyball Medicine and Walmart’s Second Opinion.