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Colorectal Cancer: New Data Suggest Rising Rates, More Advanced Disease in Young Adults 

On March 1, 2023, the first day of Colorectal Cancer Awareness Month, the American Cancer Society released some alarming new statistics regarding early-onset colorectal cancer (CRC) diagnoses: in the U.S. population, people are increasingly being diagnosed with CRC at a younger age and with more advanced disease stage. Advanced-stage CRC diagnoses have risen by eight percent in the past two decades. Additionally, early onset diagnoses rose from one in ten individuals in 1995 to one in five in 2019. While CRC in the general population is declining, rates in younger people are on the rise. 

The complete report contains CRC incidence, mortality, and screening prevalence data that were derived from multiple national databases, including: 

  • National Cancer Institute
    • Surveillance, Epidemiology, and End Results (SEER) program
  • Center for Disease Control
    • National Program of Cancer Registries
    • Behavioral Risk Factor Surveillance System
    • National Center for Health Statistics
      • National Health Interview Survey
  • North American Association of Central Cancer Registries

The report projects that of the 153,020 expected CRC cases in 2023, 13% (nearly 20,000) will be in individuals younger than 50. Seven percent of projected CRC mortality will also be in individuals younger than 50. CRC mortality in individuals under the age of 50 is also on the rise, as the mortality rate in this population has risen one percent every year since 2004. 

Rising cancer trends in the younger U.S. population point to increased exposures to causal agents, and indicate the need for research that identifies newfound risk factors. The data from this report highlights the growing concern that is early-onset CRC incidence and mortality, pointing to a portion of the population that will need more research and funding in the CRC space. 

Efforts to improve screening rates at a health care center in New York City

Racial Disparity in CRC Incidence and Mortality

Racial disparities continue to exist in CRC incidence, mortality, and survival rates. Both incidence and mortality rates in the U.S. are highest among American Indian/Alaskan Native and non-Hispanic Black individuals. Alaskan Native individuals face the highest burden of CRC incidence than any other group (88.5 per 100,000 individuals). Risk factors that contribute to disparities in the Alaskan Native population are likely a combination of environmental factors (low sun exposure, diet low in fiber, smoking, and obesity) and low access to colon health care services. Alaskan Native individuals have the lowest screening rate in the U.S. 

Black Americans are more likely to be diagnosed with metastatic CRC than any other racial or ethnic group in the nation. Black patients also experience significant disparities in care, and are 21% less likely to receive colon cancer surgery and 28% less likely to receive rectal cancer surgery. Additionally, Black patients are more likely to develop right-sided tumors, which are correlated with a poorer prognosis. 

These updated data from the American Cancer Society point to the need for future research in early-onset incidence, racial disparities, and general risk factors for CRC. Scientists should aim to identify newfound risk factors that are contributing to the trend of CRC diagnoses under 50, and to identify factors specific to high-risk racial and ethnic groups as well.

You can learn more about the signs and symptoms of colorectal cancer on this page.

 

Emma Edwards is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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Early-Age Onset Colorectal Cancer: Health Disparities in the Black Population

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the U.S., and the incidence of early-age onset CRC (EAO-CRC)—when the disease is diagnosed in those younger than 50 years—is rising. In the Black population, EAO-CRC makes up nearly 10% of all new diagnoses. The incidence of EAO-CRC in the Black population (8.4 cases per 100,000 people in 2019) is slightly lower than that of the White population (8.9 cases per 100,000 people in 2019), but this is reversed when it comes to the mortality rate. The mortality rate of EAO-CRC in the Black population is 2.4 deaths per 100,000 people, while it is 1.8 deaths per 100,000 people in the White population. Between 2015-2019, 5,329 new EAO-CRC cases were diagnosed among Black Americans.

Studies have shown that Black individuals are more likely to be diagnosed with EAO-CRC at a younger age and a more advanced stage than White individuals: 22% of White Americans receive a metastatic diagnosis compared with 26% of Black Americans. 

 

 

While additional research is needed to discern the higher incidence of EAO-CRC in the Black population, certain socioeconomic and environmental factors likely play an important role. These include limited access to proper healthcare services, the prevalence of food deserts leading to poor nutrition, and living in areas with high pollution rates. Additional resources to support research, prevention, and treatment efforts of EAO-CRC in this population are critical.  

Empowering the population via awareness and education campaigns around the early warning signs of CRC and the importance of screening in the Black community would also go a long way. Early warning signs of CRC include changes in bowel movements, blood in stool, unexpected weight loss, and continuous abdominal discomfort. If you are experiencing these symptoms, speak with your doctor. 

Additional information on prevention, symptoms, and diagnosis of CRC can be found under ‘Resources’ on the Colon Cancer Foundation’s website.

 

Emma Edwards is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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Can Circulating Tumor DNA Predict Who Will Benefit from Colorectal Cancer Chemotherapy?

Over 30% of patients with stage II or stage III colorectal cancer (CRC) and 60-70% of patients who undergo oligometastatic resection experience cancer recurrence. Stage II or III CRC is usually treated with surgery followed by adjuvant chemotherapy (ACT). However, patients with clinical and pathological risk factors only see a 10-15% decrease in cancer recurrence with standard ACT. 

Now, a new study proposes using circulating tumor DNA (ctDNA) as a predictive biomarker to guide chemotherapy treatment decisions in CRC patients. 

ctDNA is a minimally invasive biomarker that can help oncologists measure disease status and progression during cancer therapy, including the detection of molecular residual disease (MRD). In this study, researchers evaluated whether ctDNA following surgery could predict disease recurrence in early-stage CRC. 

The study enrolled 1,563 patients with:

  • Stage II or III CRC 
  • Surgically resectable stage IV CRC 
  • Recurrent CRC were prospectively enrolled in the study 

Blood samples were collected before and at predetermined time intervals after surgery (up to 18 months), and imaging was performed every six months until 18 months after surgery. MRD, defined as ctDNA positivity after surgery or therapy, is strongly associated with poor prognosis in patients with surgically resectable CRC. Of the 1,039 patients included in the ctDNA analysis, 18.0% were ctDNA positive four weeks after surgery.

Researchers discovered that patients with high-risk stage II, stage III, and stage IV CRC, who were ctDNA-positive four weeks after surgery, benefited from ACT. ctDNA was identified as the most significant risk factor for CRC recurrence in these patients, and ctDNA positivity is an important predictor of ACT benefit. 

Regardless of the pathological stage of CRC, patients with a higher risk of recurrence based on ctDNA status may benefit from ACT, while those with negative ctDNA status may be able to avoid unnecessary ACT. These findings can guide clinicians in making evidence-based treatment decisions for CRC patients.

 

Sahar Alam is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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Neoadjuvant Immunotherapy Effective for Mismatch Repair–Deficient Colorectal Cancer

Mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) colorectal cancer (CRC) is an advanced form of CRC that is highly responsive to treatment with immunotherapy, especially PD-1 inhibitors. Preliminary research results demonstrate that PD-1 inhibitors are significantly effective cancer treatments, with high response rates and sustained progression-free survival. 

A new study investigated the treatment impact of neoadjuvant PD-1 inhibitors on the long-term survival of dMMR CRC patients. The study found that PD-1 inhibitor treatment before surgery was significantly effective among patients with dMMR/MSI-H CRC.

Seventy-three patients with dMMR/MSI-H CRC who had previously been treated with PD-1 inhibitors were included in a retrospective review. The most common locations of primary tumors were in the rectum (24.7%) and ascending colon (24.7%). 79.5% of patients were treated with PD-1 inhibitor alone. The study found:

  • Nearly all patients involved in the study benefited from neoadjuvant PD-1 inhibitors, with 25% experiencing complete response.
  • 84.9% of patients experienced an objective response, with 61.6% achieving a partial response. 
  • The two-year tumor-specific overall survival and disease-free survival rates for patients who underwent surgery after PD-1 blockade were both 100%.

These findings are promising for patients with nonmetastatic dMMR/MSI-H CRC, including those with locally advanced disease. Dustin A. Deming, MD, University of Wisconsin Carbone Cancer Center, stated in an NCCN newsletter, “The treatment of mismatch repair deficient locally-advanced colorectal cancer is a highly active area of research. This retrospective analysis highlights the potential for significant treatment responses with limited toxicities for these patients treated with immune checkpoint inhibitors. It will be exciting to see how these results, and other completed and ongoing studies, will be utilized to incorporate anti-PD1 treatments into the standard-of-care for locally-advanced colorectal cancers.”

To read more about types of immunotherapy drugs and their impact on cancer care, visit Understanding Cancer Immunotherapy Research. 

 

Sahar Alam is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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Plant-Based Diets Lower Colorectal Cancer Risk in Men

Colorectal cancer (CRC), the third most common cancer and the third leading cause of cancer-related deaths in the U.S., is preventable with regular screening. In addition to routine screening, other modifiable risk factors, such as diet, play an important role in lowering the risk of CRC. For example, red and processed meats are associated with an increased risk for CRC, while diets rich in dietary fiber reduce the risk of CRC. 

A recent prospective cohort study discovered that plant-based diets rich in healthy plant foods were associated with a lower risk of CRC in men, and varied based on race, ethnicity, and tumor location. These findings signify the importance of incorporating healthy plant foods into diets and reducing meat consumption to lower the risk of CRC. 

The multiethnic cohort study included 79,952 men and 93,475 women. Three plant-based diet scores were investigated to determine the incidence of invasive CRC:

  • Overall plant-based diet index (PDI)
  • Healthful plant-based diet index (hPDI)
  • Unhealthful plant-based diet index (uPDI)

The participants completed a food frequency questionnaire with over 180 food items. PDI, hPDI, and uPDI were calculated based on scoring methods and defined food groups that included:

  • Healthy plant foods, such as whole grains, fruits, vegetables, vegetable oils, nuts, legumes, tea, and coffee.
  • Less healthy plant foods, such as refined grains, fruit juices, potatoes, and added sugars.
  • Animal foods, such as animal fat, dairy, eggs, fish and seafood, and meat. 

Each food group was associated with specific scores. 

  • High PDI scores demonstrated greater consumption of all types of plant foods. 
  • High hPDI foods showed greater consumption of healthy plant foods and lower consumption of less healthy plant foods. 
  • Higher uPDI scores demonstrated lower consumption of healthy plant foods and greater consumption of less healthy plant foods. 

The study found that a plant-based diet that includes natural, rather than processed, plant-based foods is associated with a reduced risk of CRC in men. For women, however, none of the plant-based diets were significantly associated with CRC risk. For both men and women, the average scores of PDI and hPDI were highest among Japanese Americans and lowest among Native Hawaiians. The mean uPDI was highest in Native Hawaiian men and lowest in African American men and white women. Men with higher scores for PDI and hPDI had a 24% and 21% lower risk of CRC than men with lower scores for those diets, respectively. Furthermore, no significant association was found between risk for CRC and uPDI for men.

These analyses highlight the potential significance of plant-based diets in preventing CRC and suggest that the benefits of plant-based diets can vary based on sex and race/ethnicity. The findings underscore the importance of increasing healthy and less-processed plant foods in our diet and reducing meat consumption to lower the risk of CRC.

 

Sahar Alam is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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Masculinity May be a Barrier to Completing Colorectal Cancer Screening

Colorectal cancer (CRC) mortality is preventable with regular screening. Differences in early detection screening rates lead to disparities in CRC mortality among White, Black, and American Indian/Alaska Native (AIAN) men. Complicating the issue of racial disparity observed with CRC screening rates is the psychosocial aspect of men’s health. A recent study investigated the impact of masculinity barriers on CRC screening and found that they influence CRC screening completion.  

This survey-based cross-sectional study analyzed the association between the male thought process and the successful completion of CRC screening tests. Male respondents aged 18 to 75 years from across the U.S. who self-identified as Black, AIAN, or white were surveyed. Four Masculinity Barriers to Medical Care subscale were investigated:

  • Being strong
  • Acknowledging emotions and health issues
  • Positive attitude toward medical professionals and exams
  • Negative attitude toward medical professionals and exams

The highest score, which translates into the greatest barrier for screening, was for “Being strong” and “Negative attitudes towards medical professionals and exams”

Lower scores were observed for “Acknowledging emotions and health issues” and “Positive attitudes toward medical professionals and exams”

For all men, “being strong” was associated with a 54% decreased odds of CRC screening completion. 

Reluctancy to seek and engage in preventive health services, such as CRC  screening, due to fear of presenting as weak or vulnerable is associated with men who strongly support masculine ideals. The investigation also demonstrated that Black men who scored higher on negative attitudes toward medical professionals and exams subscale had lower odds of CRC screening uptake. The sensitivity analysis of the study reflected that AIAN men had lower odds of CRC completion than Black men. 

Medical mistrust is positively correlated with masculine ideologies. Despite decreasing CRC incidence and mortality rates in adults ages 50 years and older, early-onset CRC has increased among adults younger than 50 and is predicted to increase by 90% by 2030. Considering the above masculinity barriers in future population-based and intervention research is critical for increasing men’s participation in CRC screening.

 

Sahar Alam is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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Expanding Multigene Panel Testing Criteria for Colorectal Cancer Patients

Multigene panel testing (MGPT) is a tool to identify genetic mutations that can increase an individual’s risk of a disease such as cancer. MGPT can also be used to develop a treatment plan or to help predict whether cancer will spread to other parts of the body. A recent study examined colorectal cancer (CRC) patients and found that 14.2% of patients carried at least one pathogenic germline variant (PGV), with more than one PGV identified in 1.4% of patients. 

Identification of pathogenic or likely PGVs in hereditary cancer predisposition genes can affect a patient’s treatment plan. While there is increased support for universal MGPT for certain forms of cancer, eligibility criteria for CRC are more restrictive: germline genetic testing for CRC is recommended only for a subset of patients with CRC who meet certain “high-risk criteria,” which include:

  • Diagnosis before 50 years 
  • Lynch syndrome–related cancers 
  • Having a family history of certain Lynch syndrome-related cancers 
  • Abnormalities in mismatch repair immunohistochemistry

The above mentioned study conducted MGPT across a diverse CRC population to determine whether genetic testing criteria for patients with CRC should be broadened. The results of the study found that of the 34,244 individuals who were tested:

  • 14.2% of individuals carried at least one PGV, with more than one PGV identified in 1.4% 
  • 11.9% of individuals carried a clinically actionable variant, including 9.1% carrying a PGV in a gene associated with an increased CRC/polyposis risk 
  • 5.7% of individuals carried Lynch syndrome–related PGVs 

This research study is the largest to date examining MGPT in CRC, and demonstrated high rates of clinically actionable variants detected, independent of the age at the time of testing, the number of genes on the panel, and race/ethnicity. These findings provide evidence to support the broadening of genetic testing criteria for patients with CRC, which in turn will have a significant impact on disease management, the treatment plan, and ultimately, disease outcome.

 

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Setting it Straight: The Colonoscopy Controversy

A new study published in the New England Journal of Medicine has sparked controversy—this 10-year study involving nearly 85,000 participants in Europe highlighted that colonoscopies cut the risk of colorectal cancer (CRC) only by about a fifth, far below estimates from earlier scientific studies, and didn’t substantially reduce deaths, raising the possibility that the invasive procedure is not worth it. Doctors in the U.S. are now concerned that the study’s results could cause doubt about the effectiveness of a colonoscopy, which is a recommended CRC screening approach for those 45 and older, to be conducted once in ten years. Despite the confusion about the effectiveness of colonoscopies, national news articles and gastroenterologists in the U.S. have rebuked these conclusions. 

A major limitation that experts found with the study was that only 42% of the people who were invited to get a colonoscopy actually had one. However, researchers still reported the outcomes for the entire cohort, regardless of whether or not they underwent a colonoscopy. The study found that of those who were invited to have a colonoscopy—whether they got it or not—there was an 18% reduction in developing the disease and no statistically significant reduction in the likelihood of CRC death. Many don’t believe that this is representative of what happens in the U.S., where colonoscopy is more widely accepted as a standard screening protocol compared to European countries, and was a serious shortcoming of the study. In fact, when the individuals who did not get a colonoscopy were removed from the study, the risk of developing CRC among those who did get a colonoscopy reduced by an estimated 31% and the risk of death reduced by about 50%.

As Robin Mendelsohn, MD, co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancers at the Memorial Sloan Kettering Cancer Center, argues “in order for a colonoscopy to be effective, you have to have it done”.

Andrew Albert, MD, a member of the Colon Cancer Foundation (CCF)’s Interdisciplinary Medical Advisory Council (IMAC), said, “While the NordICC trial demonstrates the need for challenging the status quo related to colonoscopy, this remains an effective screening tool, particularly for individuals at average risk who may be on the fence about going in for screening. Misinformation is dangerous, especially in healthcare. If we miss catching colorectal cancer at an early stage—which is what a colonoscopy is very good at—it can have a big impact on survival. We need to remember that CRC is preventable, and treatable when caught early.”

IMAC member Matthew A. Weissman, MD, MBA, FAAP, told CCF, “I hope that the findings of this study, which have been taken out of context by many, will not discourage folks from getting screened for colon cancer by colonoscopy or other appropriate methods, which is extremely important in early detection (and prevention) of this deadly disease.”

In an accompanying editorial in the same issue, experts point to the need for a longer follow-up time for the impact of screening colonoscopy to be realized. They also point out that the skill of the endoscopist conducting the procedure has a significant impact on the detection rate—29% of endoscopists in the trial had an adenoma detection rate below the recommended 25%. 

Consequent to this study, the American Society for Gastrointestinal Endoscopy (ASGE) issued a public statement that colonoscopy remains the best and most proven way to detect and prevent CRC incidence and death. The American Cancer Society also weighed in on the study, pointing to the high number of participants who didn’t undergo the procedure. Adam Lessne, MD, a gastroenterologist at Gastro Health in Florida told VeryWell Health that “when you take away the limitations, it’s proven again that colonoscopies do save lives and they do reduce the risk of death.” 

The bottom line is that a screening test of any kind—stool-based or colonoscopy—is better than none, and CRC is preventable with regular screening. For detailed information on various CRC screening methods and current screening guidelines, visit this page on the Colon Cancer Foundation’s website. 

 

Kitty Chiu is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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Distance, Region, and Insurance Coverage Associated With Increased Risk of Advanced Colon Cancer

Early-stage colon cancer is treatable and has a very promising survival rate. However, less than 40% of new colon cancer diagnoses are early-stage disease. Now, a new study has identified an association of distance, region, and insurance coverage with advanced colon cancer at initial diagnosis. Utilizing the Nation Cancer Database, patients 18 years or older diagnosed with colon cancer as a primary diagnosis between 2010 and 2017 were compared in terms of distance to their medical facility, region of residence, and insurance coverage. 

The study found that patients at an increased risk of advanced pathologic disease:

  • Traveled a greater distance to their medical facility
  • Lived in the Northeast, Mountain, or Central regions of the United States
  • Only had Medicaid or did not have insurance coverage

 

Sahar Alam is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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Study Finds Risk-Stratified Colorectal Cancer Screening Is Feasible and Cost-Effective

Colorectal cancer (CRC) is the third most common cancer diagnosis and the second most common cause of cancer death globally. The American Cancer Society estimates that there will be 106,180 new colon cancer cases and 44,850 new rectal cancer cases in the United States in 2022. Early detection and consistent screening reduce CRC incidence and mortality. A recent randomized controlled trial that analyzed the feasibility, adherence, yield, and related costs of various screening modalities found that a risk-adapted approach is feasible and cost-favorable for population-based screening. 

Current guidelines recommend standardized screening plans for specific age groups, with colonoscopy recommended every 10 years and a fecal immunochemical test (FIT) between 1-3 years. Implementation of risk-stratified screening can potentially allow for more frequent screening and earlier detection of CRC at a population level. This would especially be beneficial for individuals who are at higher risk of CRC. Additionally, risk-stratified screening can help health practitioners detect and introduce plans for CRC treatment at earlier stages.

The National Health Service Breast Screening Programme (NHSBSP) recently investigated the potential benefits, costs, and effectiveness of risk-stratified breast cancer screening with BC-Predict, a platform that collects self-reported risk factor information for breast cancer, analyzes the self-reported information, and invites high-risk or moderate-risk women to a conversation about prevention and early detection options. BC-Predict was found to have the potential to reduce breast cancer mortality due to early screening. It also reduced screening in women who are at lower risk, minimizing the number of false positive test results in lower-risk women. The results from this analysis are pertinent to risk-stratified screening for CRC and support the implementation of a risk-adapted approach in CRC screening.

What Did the Study Find?

More than 19,000 participants in the TARGET-C trial conducted in six cities in China were placed into one of the screening arms in a 1:2:2 ratio: 

  • One-time colonoscopy (n=3,883)
  • Annual fecal immunochemical test (FIT) (n=7,793)
  • Annual risk-adapted screening (n=7,697).

The detection rate of advanced colorectal neoplasia, CRC, and advanced precancerous lesions were the main outcomes that were monitored. The follow-up to trace the rate of advanced colorectal neoplasia for all participants was conducted over a 3-year study period. 

Over three screening rounds, the participation rates for colonoscopy, FIT, and risk-adapted screening arms were 42.4%, 99.3%, and 89.2%, respectively. The costs to the for detecting one advanced neoplasm, presented as both Chinese Yuan (CNY) and US dollar, using a package payment format were:

  • CNY6,928 ($1,004) for one-time colonoscopy
  • CNY5,821 ($844) for annual fecal immunochemical test (FIT)
  • CNY6,694 ($970) for annual risk-adapted screening.

These findings underscore the value of a risk-adapted approach for CRC screening for feasibility and cost-effectiveness, as well as for allowing for more frequent screening and earlier detection of CRC for individuals with a high or moderate risk for CRC.

 

Sahar Alam is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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