Cancer screening remains a powerful tool. Even limited screening has long-term benefits compared to no screening  and can lower the risk of cancer and related deaths. A recent study by researchers at the CDC compared data on adults who reported they had not received a colorectal cancer (CRC) screening test between 2012 and 2020 using information from the Behavioral Risk Factor Surveillance System (BRFSS). The study identified various trends, most notably that 22 states did not meet the CDC’s Healthy People 2020 goal of 70.5% adults screened for CRC.

The sample was limited to adults aged 50 to 75 years, with up to date screenings defined as one of the following:

  • Home stool-blood test within the past year
  • Sigmoidoscopy within five years with fecal occult blood test or within one year with fecal immunochemical test
  • Colonoscopy within ten years

The ‘never screened’ numbers were a composite of those who answered no to being screened or those who were not up to date. Those who declined to answer or reported uncertainty were excluded. Overall, the study identified:

  • A 5.8% decrease in unscreened adults between 2012 and 2020 
  • States with the largest improvements were also those with the largest unscreened population in 2012 

 

Despite these improvements, CRC screening goals have yet to be met and may be difficult to meet with the new Healthy People 2030 standards. The target of 74.4% screened may have been a challenge to meet, possibly further exacerbated by the COVID-19 pandemic.

Researchers noted that including just two more questions on the BRFSS in 2020, the percentage of up to date screenings increased to 71.6%. These two questions enquired about:

  • Stool DNA testing
  • Computerized tomographic colonography

It is important to note that the National Colorectal Cancer Roundtable—a membership organization established by the CDC and the American Cancer Society—has set its goal to 80% screening rates across the country.

Study authors recognized recall bias and an inability to distinguish between screening versus diagnostic tests as major study limitations. Additionally, social desirability bias and a low response rate may have also affected the results. However, financial factors and health disparities may also describe the differences between states.

Following implementation of the Affordable Care Act, researchers at the American Cancer Society found that CRC screening among low-income adults across the U.S. increased by up to 8%, with the greatest increases observed in early Medicaid expansion states. They also noted that a majority of those who were never screened also lived in a state without expansion (South Dakota). 

Nonfinancial factors such as health disparities were studied in a mixed-methods analysis conducted at the Virginia Commonwealth University’s School of Medicine. Here, researchers noted that participants of gender-specific and race-specific focus groups brought forth nuanced concerns regarding screening. This included lack of awareness of both the disease and the screening, lack of physician recommendation that is clear and rational, and fear of being diagnosed and complications associated with testing. These concerns, if unaddressed, may limit others from seeking out CRC screening.

To read more about the Healthy People 2030 CRC screening standards and the current progress, visit Healthy People 2030.

 

Kaylinn Escobar is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation. 

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.

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.

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.

Initiating regular screening at the recommended age and time interval is key to preventing and early diagnosis of colorectal cancer (CRC). An early CRC diagnosis improves survival. The American Cancer Society (2018) and the U.S. Preventive Services Task Force (2020) recommended that CRC screening should start at 45 instead of 50 years, in reaction to the growing incidence of CRC among younger people. 

All major U.S. guidelines now endorse average-risk CRC screening at 45 years of age. However, there are concerns that endoscopic capacity may be strained, that low-risk persons may self-select for screening, and that calculations of the adenoma detection rate may be diluted. 

A new study supports the recommendation that colonoscopies should start at age 45, not 50 years. In this study, researchers compared colonoscopy volumes and lesion detection rates in the U.S. healthcare system before (October 2017 to December 2018) and after (January 2019 to August 2021) the new guidelines were issued. They included 7,990 patients who had undergone colonoscopies from October 2017 through August 2021: 4,266 first-time colonoscopies and 3,724 re-screening colonoscopies. 

Researchers found that:

  • After the screening age for colonoscopy was lowered, younger people were more likely to undergo the procedure
  • Among people ages 45 to 49, first-time screening rates increased from 3.5% in the period before guidelines were changed to 11.6% after they were updated 
  • First-time colonoscopies were still largely performed in patients ages 50 to 54 in both time periods, while re-screening colonoscopies showed a shifting trend toward older ages
  • Patients ages 60 to 64 were the most likely to undergo re-screening during both time periods 

They concluded that in our healthcare system in the early contemporary era of updated CRC screening guidelines, screening colonoscopy volume among 45- to 49-year-old patients has increased modestly, and lesion detection rates in 45- to 49-year-old patients have not decreased as might have been seen if low-risk persons were self-selecting for screening. The authors acknowledged that their findings were based on a single healthcare system and that national data will be important to assess the impact of the revised guidelines. 

 

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

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.

 

Genetic factors play an important role in the development of colorectal cancer (CRC). Some people have inherited genetic syndromes that increase their risk for colon cancer. Genetic testing looks for these inherited syndromes along with changes in DNA that are associated with a greater likelihood of developing cancer. 

What is Genetic Testing for CRC?

Genetic testing looks for changes in your DNA that are known to be associated with an increased risk of cancer. Generally, there are two ways that genetic testing may be used: 

  • Before a person develops cancer to determine their level of risk
  • Following a cancer diagnosis to see if genetic changes may have contributed to the cancer

According to the American Cancer Society, genetic tests can help show if members of certain families have inherited a high risk of CRC due to inherited cancer syndromes such as Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC) or familial adenomatous polyposis (FAP).

Who is Considered “High-Risk”?

Those with a family history of CRC may benefit from speaking to their primary care physician, oncologist, or surgeon about the importance of genetic testing to identify if there was a mutated gene that predisposes them to cancer. You may be a good candidate for genetic testing for CRC if you have:

  • Close family members, such as parents, children, or siblings, who have been diagnosed with CRC
  • Many people on one side of your family who’ve been diagnosed with CRC
  • A personal or family history of CRC diagnosis at a young age
  • A personal or family history of an inherited genetic syndrome that increases CRC risk
  • A personal or family history of multiple cancers
  • A strong family history of CRC or other cancers that are associated with an inherited genetic syndrome
  • More than 10 adenomatous polyps found during CRC screening

What Can I Expect With the Procedure?

If your doctor believes that you’re a good candidate for genetic testing, they’ll likely refer you to a genetic counselor. Genetic testing is typically done using a blood sample. However, it may also use a sample of saliva, cheek cells, or skin. This sample will be sent to a specialized lab that will run the test. After a few weeks, your results will be sent over to your doctor or genetic counselor and you’ll be contacted to discuss your test results and next steps.

How Much Does Genetic Testing for Colon Cancer Cost and is it Covered by Insurance?

Genetic testing can be expensive and can cost between $100 to over $2,000, depending on the nature and complexity of the test. Many insurance providers will cover the cost of genetic testing and genetic counseling if it’s considered medically necessary. 

  • Most private health insurers cover genetic counseling and testing with low- or no out-of-pocket costs for people who meet certain personal or family cancer history criteria.
  • Medicare covers genetic testing for people with a cancer diagnosis who meet certain criteria; you must have a cancer diagnosis to qualify for coverage of genetic testing for an inherited mutation.
  • Medicaid programs cover BRCA genetic counseling and testing for qualifying individuals, including those with a known mutation in the family, or specific personal and/or family history of cancer for all but two states: Alabama and Rhode Island.

Nevertheless, always check with your insurance provider to see what’s covered before getting tested. For additional information about insurance coverage, please visit: Paying for Genetic Services.

 

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

Clinical decision support systems (CDSS) are computer-based applications used to analyze data within electronic health records (EHRs). CDS algorithms are progressively being integrated into healthcare systems to expand patient care. However, research and development in ethical frameworks have uncovered that CDS applications can perpetuate bias in healthcare. A recent EHR quality improvement study has revealed significant differences in family history accessibility, availability, and comprehensiveness based on sex, race and ethnicity, and language preference. These findings propose that historically medically underserved populations are excluded from identification from CDS tools based on family history information, unintentionally reinforcing existing healthcare disparities and potentially creating more disparities in healthcare systems.

 

decision support system

Image Credit: CDC on Unsplash

The Colon Cancer Foundation (CCF) spoke with Alessandro Mannucci, MD, who received the 2022 Colon Cancer Foundation and CGA Colorectal Cancer Research Scholar Award to present his work at the 2022 CGA-IGC Annual Meeting in Nashville, TN, November 11-13. Dr. Mannucci, a medical resident in gastroenterology and gastrointestinal endoscopy at the San Raffael Hospital, Milan, Italy, will be presenting his work titled ‘Lynch Syndrome is Associated with Fecal and Salivary Dysbiosis’.

CCF: What is the importance of the gut and the microbial flora in the human body, and how do they influence our well-being?

Dr. Mannucci: Broadly speaking, the microbiota is made up of many different cell types, including bacteria, viruses, fungi, and other kinds of microorganisms. However, our study specifically focused on bacteria because it is known that we have way more bacteria in our body than human cells. That alone indicates the significant impact of the microbiome on different phases of our life—from childhood to adulthood. 

The disruption of a healthy microbiome equilibrium causes the components of the microbiome to converge toward a proinflammatory environment in several ways. Certain species increase the risk of colorectal cancer [CRC]. Organisms that increase in numbers in the presence of CRC are generally proinflammatory. This understanding has come simultaneously with the realization that inflammation is one of the new pillars of cancer. The inflammatory environment is a disruption that is particularly important when studying the colon because the colon is the first organ in direct contact with the microbiome. 

CCF: Can you tell us the importance of this fact in your research? 

Dr. Mannucci: In our study, we had a suspect: the microbiome. While the microbiome is known to play a role in turning a normal cell cancerous, this association had not been investigated in the context of the hereditary Lynch syndrome [LS]. Mutations in one of five genes can lead to LS. 

There is a spectrum of manifestations of LS, the most important of which is CRC, although developing the cancer is determined by penetrance. We were interested in knowing if the microbiome has a role in this process.We wanted to know if the microbiome in individuals with LS who had not yet developed cancer, differed from those without LS. While it may be difficult to explain a cause-and-effect relationship, it is important to understand why a difference exists. Germline pathogenic variants may influence the formation, conformation, and diversity of the microbiome, or vice versa. Interestingly, we found that the fecal microbiota was significantly different among those with LS, but we need more data.

CCF: What is the relevance of microorganisms in the oral cavity? 

Dr. Mannucci: In individuals with LS, the cells within their mouth are also mutated. So we decided to test the differ

 Alessandro Mannucci, MD

ence between the fecal and oral microbiota among those with and without LS and found that not only is the fecal microbiota different, which you would expect because LS is associated with an increased risk of CRC, but we also observed a proinflammatory change in the oral microbiota. We now know that the oral microbiota of patients with LS differs from that of healthy individuals, which raises the question that pathogenic variants inside the mouth may interact with microbiota species that cause a proinflammatory shift. 

Another hypothesis is that individuals with this particular hereditary predisposition to CRC may also have a predisposition to orthodontic diseases. While we currently have limited understanding of this association and are testing the hypothesis, our discovery of the unexpected difference of a proinflammatory environment led us to suppose that maybe something else was at play.

What is interesting when we talk about scientific studies is not only what you are interested in, but also what you compare it to. In our case, we compared LS patients without cancer diagnosis to unrelated, healthy patients. So we did not have within-family control, which other investigators might want to look at–within the family or individuals with LS in different age groups.

CCF: How long will the subjects in your study be followed?

Dr. Mannucci: While we usually follow patients throughout their lives, five to ten years of follow-up will give us more insight. The idea is that if there is a proinflammatory environment within that patient, it could trigger cancer at an earlier age. To test that hypothesis, we are collecting samples of relatively young individuals, and we want to follow them and see if they develop cancer. The mean age of patients with LS was 48 years plus or minus 16 years.

CCF: Does diet influence microbial flora and the balance of pro- versus anti-inflammatory microbial flora in the oral cavity and the gut?

Dr. Mannucci: You raise a very, very interesting point! The microbiota is adaptable, and it can change very rapidly. There is some robustness to it, meaning you shape the health of your microbiome during your youth and by the time you reach adolescence or young adulthood, your microbiota is pretty much set. However, it can change based on your diet. 

One of our study limitations is that we could not control for diet. We could control other factors that can influence the changes within the microbiota itself, such as age, sex, smoking, the presence of cancer, or chemotherapy treatment—factors that can modify the shape, overall biodiversity, and the general composition of the microbiota.

However, we could not control the overall dietary composition. In the future, we may control our patients’ diet and place them either on a Western diet as opposed to a Mediterranean diet or a modern diet. 

Assuming that individuals with a higher risk of CRC follow an anti-inflammatory diet, you would expect to see an anti-inflammatory microbiota. We found the opposite; we found a proinflammatory change within the microbiota. While we are planning to control for participant diets in future studies, an alternative approach would be to include individuals with different genetic backgrounds and eating similar diets to investigate the differences in their microbiota. 

But remember, this is currently a hypothesis. What we know now is that these genetic predispositions are associated with a difference in the microbiota composition, and that difference itself is a proinflammatory environment. We don’t know the cause-effect relationship or how that can be altered, yet.

CCF: What would be a key takeaway from your study findings?

Dr. Mannucci: A key takeaway is that we’re developing a tool to better understand who does or does not get cancer. Hopefully, it will become a tool or a target to reduce the risk of cancer. I completely agree that diet can be a big influence. So maybe in the near future, we will be able to tell our patients that if they stop smoking, regularly exercise, reduce the intake of fatty foods, and if they have a specific kind of diet, they can reduce their risk of CRC. The microbiota has the potential to become an instrument for reducing the risk of cancer, but we are not there yet.

Thank you to Sahar Alam, CCF’s Colorectal Cancer Prevention Intern, for her assistance with this post.

As we emerge from the initial waves of COVID-19, patients may have been reluctant to take more time out of their life for a colonoscopy prep, procedure, and recovery. Fortunately, non-invasive stool-based screening tools, such as fecal immunochemical tests (FIT) and multi-target stool DNA (mt-sDNA or Cologuard), are practical options that allow patients to provide a sample in the comfort of their home and could address access and care gap issues as they are less expensive. 

According to a new study presented during the Scientific Forum at the American College of Surgeons Clinical Congress 2022, these non-invasive stool-based screening methods are equally effective for screening for early-stage colorectal cancer (CRC). Pavan K. Rao, MD, a general surgery resident at Allegheny Health Network in Pittsburgh, Pennsylvania, presented study results that evaluated 117,519 enrollees within the Highmark claims database who underwent CRC screening in 2019. The researchers found:

  • About 60% of patients taking either the fecal immunochemical test or the DNA test at home instead of having a routine colonoscopy had early-stage cancer, but a FIT detected it at one-fifth the cost. 
  • The total annual costs for the tests were $6.47 million—$1.1 million for a FIT (about $24 per test) and $5.6 million for mt-sDNA (about $121 per test). Costs were calculated using Medicare reimbursement rates.
  • Transitioning all non-invasive CRC screening to FIT would result in $3.9 million in savings annually in the study population. 

Similarly, these results support previous studies out of Japan and the Netherlands that found FIT was more cost-effective than other types of non-invasive CRC screening tests. This provides our healthcare system with an efficient alternative at a reduced cost that maintains patient outcomes without compromising the quality of care.