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How Quickly Should a CRC Patient Start Their Treatment? Does It Matter?

By Parker Lynch

In a recent study conducted in Canada, 5,026 patients with colorectal cancer (CRC, all younger than 50) were evaluated between 2007 and 2018. This study evaluated the time between a patient’s first presentation with CRC and their treatment initiation. The overall objective of this study was to determine if a longer time from presentation to treatment start would result in worse survival rates for CRC patients, particularly those under 50.

Relation Between Treatment Start and Disease Outcome

The median age of the participants was 44 years, with about an equal number of males and females:

  • 25.2% overall had metastatic disease
  • 31.2% had rectal cancer

The lower-urgency subset consisted of 2,548 patients. Patients with metastatic CRC had shorter median (IQR) overall intervals (83 days) compared with those with less advanced disease. Five-year overall survival was 69.8%. Overall intervals longer than 18 weeks were not associated with significantly worse overall survival (OS) or cancer specific survival (CSS) compared with those waiting 12 to 18 weeks. Additional analysis by the researcher where patients were stratified by stage of disease  did not show significantly worse OS or CSS with increasing overall interval lengths.

One would expect the findings to support that a later treatment start would result in worse outcomes for the patient. In other words, starting treatment as soon as possible would yield the best prognosis for patients. However, this study found something quite different: time from presentation to treatment was not associated with advanced disease or poor survival. This finding insinuates that a patient has a little bit of “leeway” in terms of the time it takes for them to begin their actual treatment, without having to worry that this delay will correspond to decreased survival.

Another Study With a Different Perspective

In another study, the administrative time of adjuvant chemotherapy following a curative surgical procedure for stage 3 CRC was evaluated. Specifically, researchers wanted to determine if there was a so-called “sweet spot” for when a patient should begin chemotherapy to maximize their chances of survival. 

In this study, 159 patients with stage III CRC, who had undergone a curative resection, were enrolled. Patients were categorized into 3 groups representing different timings to initiate chemotherapy treatments:

  • less than 2 weeks (group 1)
  • 3 to 4 weeks (group 2)
  • more than 5 weeks (group 3)

The OS and relapse-free survival rate (RFS) were analyzed to evaluate the effectiveness of adjuvant chemotherapy. The 5-year OS was:

  • 73.7% in group 1
  • 67.0% in group 2
  • 55.2% in group 3

The 5-year RFS was:

  • 48.8% in group 1
  • 64.7% in group 2
  • 57.1% in group 3

When specifically considering CRC patients who have undergone resection procedures, it was loosely determined that chemotherapy should be administered 6-8 weeks after one undergoes an operation. However, the administration prior to the 6-week mark didn’t result in a statistical difference in outcomes.

This, however, should not encourage patients to “wait out” their cancer; rather, that time should still be spent on interactions with providers to come up with a treatment plan. CRC, on average, takes around two years before it metastasizes to other organs such as the lungs, liver, lymph nodes, peritoneum, etc. Though this sounds like a lot of time, it is always best to be aware of one’s condition as soon as possible. 

The Dangers of Misdiagnosis 

When CRC is discovered at an advanced stage, it can be one of the deadliest and most difficult cancers to tackle. This is why misdiagnosis is such a prominent fear and active issue within the CRC community, particularly among younger CRC patients, who often struggle with getting the right diagnosis in the first place. 

When a younger person experiences CRC symptoms, it is often easy for them to be excused as hemorrhoids, irritable bowel syndrome, inflammatory bowel disease, or other gastrointestinal conditions. When properly diagnosed after the initial misdiagnosis, patients would have typically already progressed to a more intense and worrisome stage of CRC, therefore making their treatment plans and overall survival rates more complicated. 

Every CRC patient is different–they may vary in age, sex, predisposing health, stages of CRC, etc. Therefore, it is impossible for researchers to determine the perfect time in which every single patient should start treatment while keeping their survival rates in mind. However, the dangers of waiting too long are known. Though beginning chemotherapy treatments early (less than six weeks after resection procedures) don’t typically have a significant impact on one’s survival rate, significant delays in initiating treatment may result in negative outcomes. 

Parker Lynch is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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Colon Capsule Endoscopy with AI: A Promising Approach for Early Cancer Detection

By Deepthi Nishi Velamuri

Colon cancer is the third most common cancer in the U.S., and early detection is essential for improving survival rates. Colon capsule endoscopy (CCE) is a minimally invasive procedure that uses a small camera to examine the colon. It is a good alternative to colonoscopy for people who are unable to undergo traditional colonoscopy, such as those who are obese or have a history of bowel obstruction.

However, CCE can be time-consuming and labor-intensive to analyze. This is where artificial intelligence (AI) can help. AI-powered software can be used to automatically analyze CCE footage, identify potential polyps, and flag them for further review by a doctor.

A study published in the journal Colorectal Disease found that AI-powered software was able to detect polyps with a high degree of accuracy. The study also found that AI-powered software could reduce the time required to analyze CCE footage by up to 70%.

These findings suggest that AI-powered software could make CCE a more feasible option for wider use. This could lead to earlier detection of colon cancer and improved survival rates.

Here are some of the benefits of using AI-supported footage analysis in CCE:

  • Increased accuracy: The software can identify polyps with a high degree of accuracy, even those that are small or difficult to see.
  • Reduced time: The software can reduce the time required to analyze CCE footage by up to 70%. This frees up time for doctors to focus on other tasks, such as providing patient care.
  • Improved patient experience: The software can make CCE a more comfortable and convenient procedure for patients. This is because patients do not have to undergo sedation or gas insufflation, and they can return to their normal activities sooner.

Overall, AI-supported footage analysis is a promising approach for improving the accuracy, efficiency, and patient experience of CCE. It is a technology that is worth watching as it continues to develop.

 

Deepthi Nishi Velamuri is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

Image by Gerd Altmann from Pixabay

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Genetic Disparity May Contribute to Worse CRC Outcomes Among African-Americans

Health disparities are present in a multitude of different health issues and drive inequity among populations. These populations can be defined by factors like race, income, gender, or even geographic location. Improving access to colorectal cancer screening involves addressing these populations. Researchers can utilize data to identify geographic disparities, but understanding racial disparities becomes more complicated due to sociodemographic and cultural considerations. Yet, scientists at the Memorial Sloan Kettering Cancer Center (MSKCC) may have discovered reasons for these disparities on a microscopic level.

MSKCC researchers analyzed DNA sequencing data of over 4,000 patients at the hospital over the course of 8 years and compared it to ancestry information. They found that patients with African ancestry had shorter median survival post-diagnosis, had less accurately predicted outcomes, and were less likely to have the genetic mutations needed to be considered for immunotherapy. Overall survival  for the African ancestry group was only 45.7 months post-diagnosis compared to 67.1 months for the European ancestry group.

Mutations in the adenomatous polyposis (APC) gene, which is a known tumor suppressor, are associated with better CRC outcomes. However, this mutation appeared to make no difference in survival for Black patients while improving survival rates among European, East Asian, and South Asian CRC patients.

Disparity in Treatment Response

When it came to treatment, the African ancestry group had less genetic markers for effective immunotherapy treatment as defined by the FDA. While the European ancestry group had a 20.4% qualification rate, the African ancestry group had only 13.5%. Even compared to those who did not qualify for immunotherapy treatments based on FDA guidelines, those with African ancestry still experienced less actionable genetic alterations than the European group (5.6% and 11.2% respectively). Researchers propose that this may be due to fewer BRAF V600E mutations in the African ancestry group. Patients who carry this mutation typically respond well to certain targeted treatments.

A limitation of this study is its exclusion of environmental and lifestyle factors that are important in CRC outcomes.

Addressing health disparities in screening and treatment benefits researchers and community efforts by identifying how and where to implement interventions. This study suggests that these large-scale issues may have solutions hidden within the population of interest itself.

 

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

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Fitness and Reducing Colon Cancer Risk: It’s Never Too Late to Start!

The benefits of exercise for overall health and disease prevention are well known. While research overwhelmingly points to physical activity as a protective factor against colorectal cancer, more research is necessary to delineate how the timing of physical activity during one’s life impacts the risk of developing colon cancer. In a recently published study, researchers examined the differences in colon cancer incidence in relation to levels of physical activity at different stages of life. 

Researchers conducted a baseline survey in 1995 and 1996 of adult men and women to measure exposures to moderate-to-vigorous physical activity (MVPA) and several other lifestyle-related factors among nearly 300,000 adults (50-71 years). Study follow-ups ceased in 2011 or following any diagnosis of colon cancer or death. 

In the primary exposure assessment, participants were asked to report and quantify MVPA they had participated in at various stages of their life: at ages 15-18, 19-29, 30-35, and in the previous decade. MVPA levels were measured by time:

  • Rarely or none
  • Less than 1 hour a week
  • 1-3 hours a week
  • 4-7 hours a week
  • Greater than 7 hours per week 

Pattern Recognition and Impact on Colon Cancer Risk

Researchers identified specific patterns of MVPA:

  • Maintaining the same general level of physical activity throughout the life course (whether low, moderate, or high levels of MVPA) 
  • Raising levels of physical activity during the life course, either earlier or later in life (increasers) 
  • Reducing the amount of MVPA over time, either earlier or later in life (decreasers) 

Several key findings emerged from these patterns: 

  • Participants who maintained high MVPA levels throughout their life had a 15% lower risk of colon cancer than those who maintained low MVPA levels throughout their life
  • Participants who increased MVPA levels at a younger age had a 10% reduced risk of colon cancer, and participants who increased MVPA levels at an older age had an 8% reduced risk of colon cancer
  • Decreasing MVPA levels during the life course resulted in a 12% higher risk of colon cancer incidence when compared with individuals who maintained low MVPA levels throughout their life

These findings suggest that individuals who consistently engage in MVPA throughout their life and those who increase MVPA levels during their life have a lower risk of being diagnosed with colon cancer. They provide hope to individuals who may begin their fitness journey later in life. 

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

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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

Man

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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