Advanced-Stage CRC Increasing in Younger Adults, With Disparities Among Black, Hispanic Populations: Jordan Karlitz, MD

Colorectal cancer (CRC) became the leading cause of cancer-related death among US adults younger than 50 in 2023, rising from the fifth-leading cause in 1990, according to a research letter published last month in JAMA.¹

Shortly after these findings were published, The American Journal of Managed Care^® (AJMC^®) spoke with Jordan Karlitz, MD, about what is driving this shift, key CRC risk factors and symptoms to recognize, and strategies to prevent or detect the disease early. Specifically, in the first half of the interview, he highlights factors contributing to the increase in mortality among younger adults, important risk factors and warning signs, and disparities in incidence and mortality.

Karlitz is the senior medical officer of screening at Exact Sciences and holds a voluntary teaching position at the University of Colorado School of Medicine. He previously served as chief of the gastroenterology and hepatology division at Denver Health Medical Center.

This transcript has been lightly edited for clarity.

AJMC: CRC is now the leading cause of cancer-related deaths among patients under 50. What factors do you think are driving this increase?

Karlitz: I think there are a handful that are really critical. I would say one of the big ones is not getting screened on time at age 45. As we know, the screening age was moved down from 50 to 45 for average-risk individuals. I want to place emphasis on that because if you're at higher risk based on family history, you may need to be screened before age 45.

But I think a big issue is not getting screened on time at 45 and waiting for 50 or even later. So, once you hit 45, you want to get screened because a lot of the mortality that we're seeing is actually in the age group of 45 to 49.

Another issue is delays in diagnosis. If you have symptoms like rectal bleeding or abdominal pain, there could be delays in diagnosis, particularly in younger individuals. I'm talking about people in their 40s, 30s, and 20s, so really young people who are having symptoms. A lot of times, they may not think the symptoms are important, or even the provider may not think that they're concerning.

You really need to act on symptoms. You want to tell your provider about them, advocate for yourself as a patient, and try to get the workup you need to figure out what your symptoms are. You really do not want to delay diagnosis.

Another core issue is a family history of cancer. Many people don't actually know their cancer family history, and it's really important to know it, because for CRC specifically, you may need to be screened well before age 45, depending on that history. You need to know that information and relay it to your provider.

The other issue, of course, is risk factors, specifically modifiable risk factors. In early-onset CRC and also CRC at a later age of onset, there are a number of risk factors, including a Western diet: processed food consumption, red meats, cold cuts, and foods and beverages that are high in sugar. A higher body mass index, sedentary lifestyle, smoking, and alcohol, all of these risk factors are also at play in younger individuals.

But the good news is that a lot of these are modifiable. If people are aware of these risk factors, they may be able to make an impact, decrease those risk factors, and hopefully decrease the risk of developing polyps and CRC.

AJMC: What should younger adults know about CRC risk and warning signs?

Karlitz: One thing to preface before I even go into detail on some of the risk factors and things we already talked about is that a lot of CRCs are asymptomatic. You may not have any family history, and you may not have any symptoms, which is why we have CRC screening recommendations. You have to get screened on time at your recommended age. Again, average risk screening at age 45, and potentially younger depending on your family history.

It’s really important to know that if you're asymptomatic, that doesn’t mean you don’t have something; that’s the importance of getting screened. Once you have symptoms, you're not really talking about screening anymore; you're talking about diagnostic workup.

Some important symptoms and signs that could be present if you do have CRC include rectal bleeding, abdominal pain, and a change in bowel habits. You could have lab abnormalities, like iron deficiency anemia. These things may not always be associated with CRC, but they can be and can be very concerning for CRC.

Patients definitely want to check these things out with their providers. In terms of rectal bleeding, a lot of times providers will say, “Oh, you're only in your 20s; this is not a big deal. It may be a hemorrhoid,” but you really cannot assume that.

Over my career, I've seen cases where younger individuals had rectal bleeding, maybe went to the emergency room, and were told it was hemorrhoidal bleeding. Then, months later, they were diagnosed with CRC. I think we really need to be vigilant about these concerning symptoms and work them up.

The other thing that supports this is the rising mortality for CRC in younger individuals. According to a recent piece published in JAMA, unfortunately, 3 out of 4 younger individuals diagnosed with CRC are actually diagnosed with advanced-stage disease. Again, we need to be vigilant about risk factors, and we need to take symptoms seriously and get workups done quickly.

AJMC: Are there notable disparities in CRC incidence or mortality among racial, ethnic, or socioeconomic groups? If so, what are they, and how can they be addressed?

Karlitz: Before I was at Exact Sciences, I did a lot of work in CRC epidemiology, particularly using the SEER [Surveillance, Epidemiology, and End Results] database. We published a number of papers, including one in Cancer Epidemiology, Biomarkers & Prevention.²

It looked at the changes in the proportion of advanced-stage CRC, so the percentage of advanced-stage cases out of all CRC diagnoses. We looked at how that’s shifted over the past decade or so.

What we found was an increase in the proportion of advanced-stage disease among younger individuals. We also performed substratification by race and ethnicity and saw that some of the largest increases in late-stage proportion over the past 10 years or so were in the non-Hispanic Black and Hispanic populations, so that is obviously highly concerning. Some of these cases are in individuals in their 20s and 30s, so really young.

I think it’s really critical that we’re optimizing screening rates, starting at age 45 for average-risk individuals. Knowing your family history is also essential so you can get screened before age 45 if needed. The other issue with family history is that if you have a strong family history of cancer, CRC, or even other cancers, you may need genetic testing and genetic counseling to identify syndromes like Lynch syndrome, which could be associated not only with CRC but also with other cancers, including ovarian cancer, uterine cancer, and several others.

References

1. McCormick B. CRC becomes leading cause of cancer-related death in younger adults, highlighting prevention gaps. AJMC. January 26, 2026. Accessed February 24, 2026. https://www.ajmc.com/view/crc-becomes-leading-cause-of-cancer-related-death-in-younger-adults-highlighting-prevention-gaps
2. Montminy EM, Zhou M, Maniscalco L, et al. Shifts in the proportion of distant stage early-onset colorectal adenocarcinoma in the United States. Cancer Epidemiol Biomarkers Prev. 2022;31(2):334-341. doi:10.1158/1055-9965.epi-21-0611