Further research the nature, biology, and implications of colorectal cancer, throughout the continuum of age (while also considering younger adults versus older adults). Understanding parameters, including stage, location, histopathology, and underlying genetic and molecular “drivers.”

Strategies:

1. Explore further themes of etiology of early-age onset colorectal cancer; looking beyond the known risk factors and applying the most recent research developments.
2. Consider biology, risk exposure, and socioeconomic status in development.
3. Create an index of common research and reporting metrics.
4. Share common data and registry information.
5. Support research to develop a stronger understanding of symptomatology and clinical presentation of patients.

Research the role and impact of health disparities in those developing colorectal cancer, exploring factors such as biology and socioeconomic status; research to inform evidence-based interventions in areas of biology and healthcare policy.

Strategies:

1. Analyze existing and emerging “hot spots” for colorectal cancer incidence, particularly in younger groups to examine factors for increased incidence.
2. Specifically analyze colorectal cancer tumor characteristics, such as anatomic location, somatic mutations, microsatellite instability, and epigenetics.
3. Further understand the potential environmental risk factors for early-age onset colorectal cancer and how these could contribute to disparities by race/ethnicity.
4. Explore possible policy and research strategies to inform evidence-based interventions in areas of biology and healthcare policy.

Improve dissemination and implementation (D&I) (spreading the information and putting into practice) of evidence-based and population-based strategies for genetic and hereditary colorectal cancer, specifically Lynch syndrome.

Strategies:

1. Advocate for Commission on Cancer (CoC) to include multigene panel testing/universal testing measure for Lynch syndrome.
2. Advance the Access to Genetic Counseling Services Act Center for Medicare and Medicaid services coverage for genetic counseling and testing, and possible alignment with the Cure 2.0 legislation.
3. Collaborate with the President’s National Advisory Board to further engage initiatives promoted through the NCI Moonshot for further Blue Ribbon Panel recommendations.
4. Further integrate screening for Lynch syndrome as a measure for the College of American Pathologists (CAP)/American Gastroenterological and The Merit-based Incentive Payment System (MIPS).

Progress research and exploratory science to advance our knowledge of Lynch syndrome. 

Strategies:

1. Prioritize vaccine research for Lynch syndrome.
2. Further chemoprevention research for Lynch syndrome and other hereditary colorectal cancer syndromes.

Dissemination of guidelines for the average-risk population for screening by organizations, such as the American Cancer Society,  resulted in increased engagement of the population in preventive screening and led to marked reduction in disease incidence and mortality in older adults (i.e., those over age 50)

In May 2021, the U.S. Preventive Services Task Force (USPSTF) officially lowered the recommended age of screening from 50 to 45, following extensive review of research, as well as recognition of the increasing incidence of colorectal cancer among young adults

More than 40 million people in the U.S. are eligible for colorectal cancer screening.

Challenges

• The national screening rate based on 2018 Behavioral Risk Factor Surveillance System (BRFSS) data is 67%-68%. This accounts for those ages 50 and over.

In 2021 when the USPSTF reduced the screening age from 50 to 45, the eligible population increased by an estimated 60%, expanding the population of people who need to be screened from 27 million to 44 million. 

Compounding this challenge is the rapidly growing aging population. The diagnosed incident cases of colorectal cancer are expected to increase by an annual growth rate of 1.9% from 2018-2028.

• The multitude of modalities and options for screening differ with regard to advantages and disadvantages. While there is great opportunity in choice of options, the challenge is to keep the public and medical providers fully up-to-date, so as to foster their ability to make informed decisions as to which option is best for them. 

Which test to recommend continues to be controversial within the healthcare community. Debates continue to complicate public health efforts over colorectal cancer screening methods, age to start and to stop screening, and post-colonoscopy/polypectomy surveillance guidelines.

Opportunities

• National and local efforts to bring awareness of the benefits of colonoscopy screenings have paid off: When people are screened, colorectal cancer is prevented or caught early. Screening saves lives.
• In December 2020, the Removing Barriers to Colorectal Cancer Screening Act of 2020, which waives co-insurance charges for average-risk colorectal cancer screening of Medicare beneficiaries, regardless of whether tissue is removed during the test, was passed. This Act will be phased in during an eight-year period beginning in 2022.
• Related to quality measures and incentives for providers to keep cancer prevention as a topic priority, two very important measures are in effect. The first is the Healthcare Effectiveness Data and Information Set (HEDIS), a tool used by more than 90% of America’s health plans and is a comprehensive set of standardized performance measures. The measure consists of members ages 50-75 who receive the appropriate screening for colorectal cancer
• The second is within Medicare: Colorectal cancer screening is also now a National Quality Strategy Domain: Effective Clinical Care. This measure is to be submitted once per performance period for patients seen during that period. This measure may be submitted by Merit-based Incentive Payment System eligible clinicians
• Integrating quality measures and incentives with key indicators and benchmarks for success have been proven to help ensure providers meet designated metrics. As a result, providers are more likely to recommend colorectal cancer screenings to their patients.
• The Centers for Disease Control and Prevention (CDC) currently funds the Colorectal Cancer Control Program (CRCCP) and is focused on increasing colorectal cancer screening rates in 35 states within the safety net and primary care clinics in reaching those patients who have the lowest screening rates. 
• This is one of the largest investments in screening the medically underserved, and understanding and disseminating best practices. The Centers for Disease Control also has a variety of mechanisms in their funding portfolio to research implementation of colorectal cancer screening, as well as data repositories.

Family History and Increased Risk 

Guidelines for those who are at increased and high-risk are well-established for colorectal cancer screening. The most common guidelines include U.S. Multi-Society Screening Guidelines, American College of Gastroenterology, and the American Gastroenterology Society. 

We have identified genetic and hereditary syndromes and risk factors that we know increase the likelihood of colorectal cancer. The lifetime risk of colorectal cancer in average-risk individuals is approximately 4.5% and approximately double in individuals with a positive family history. 

Familial colorectal cancer may have some component that is genetic in origin or may be an effect of shared environmental exposures. It is estimated that approximately 10% of the general population ages 30-70 years old have a first-degree family history affected by colorectal cancer and up to 30% will have a first-degree family member or second-degree relative with colorectal cancer.  

It is also well-established that Inflammatory Bowel Disease (IBD), including either ulcerative colitis or Crohn’s disease, also increases risk of colorectal cancer. 

Challenges

• Despite being at increased risk for colorectal cancer due to positive family history, first-degree relatives (FDR) are not always screened according to guidelines. 

One study found that 40% of individuals with a family history of colorectal cancer were screened appropriately according to the American Gastroenterological Association guidelines. ⁽³⁴⁾

Other research suggests that 47% of individuals at increased risk for colorectal cancer (defined as a FDR diagnosed before age 55, or two relatives diagnosed with colorectal cancer) adhered to colorectal cancer screening guidelines. ⁽³⁴⁾

Results of these studies indicate an opportunity to increase screening adherence among first-degree family members of colorectal cancer patients. 

This does not take into account advanced adenomas within families and the need for colonoscopy screening, which is another area of attention that could be addressed for the biggest potential in colorectal cancer prevention. ⁽³³⁾

Opportunities

• The Affordable Care Act ensures coverage of any Grade B or higher USPSTF recommendation, which includes some genetic referral guidelines, cancer screening with no co-pays or co-insurance, and allows parents to keep their children on their plans until age 26 if the children are still in school. ⁽¹²⁾

Additionally, the Genetic Information Non-Discriminatory Act prevents health insurance and employment discrimination based on genetic test results or family history. ⁽¹²⁾

• As colorectal cancer screening evolves and we continue to push forward, it will be critical that we find mutually beneficial partnerships that can produce groundbreaking research and innovation that solves complex problems, drives economic growth, and creates a more skilled workforce. 

Improve dissemination and implementation (spreading the information and putting into practice) of the evidence-based colorectal cancer screening interventions for the average-risk population.

Strategies:

1. Advocate for stronger integration of preventive screening for comprehensive care for the average-risk population as a “default.” No longer recommending only colorectal, breast, cervical, lung, and other screening recommendations in isolation, by body parts, but rather recommending screening guidelines as a whole. 
2. Provide a dedicated approach to target-specific screening interventions and campaigns to reach communities with the lowest colorectal screening rates.
3. Continue state and federal level policy work to remove out-of-pocket costs for colonoscopy following a positive noninvasive screening test.
4. Advocate for a HEDIS measure that will ensure completion of follow-up colonoscopy for positive noninvasive tests and abnormal screening, denoting that preventive screening is not complete until a follow-up colonoscopy is completed.
5. Create consumer-driven awareness by advocates with payers and policymakers.

Improve dissemination and implementation of the evidence-based colorectal cancer screening for the increased, high-risk and symptomatic patients.

Strategies:

1. Increase the number of patients who have completed family history and referral for genetic and hereditary colorectal cancers, including family history of advanced adenomas, colorectal cancer, and other genetically linked cancers.
2. Increase screening rates for those who have first-degree family members with hereditary and genetic adenomas, colorectal cancer, and other genetically linked cancers.
3. Reduce stigma for patients who have signs and symptoms of colorectal cancer for more timely follow-up for colonoscopy.

Further research and examination of colorectal cancer screening uptake for those younger than age 50 to reduce early-age onset colorectal cancer.

Strategies:

1. Research to help define common signs and symptoms to create a clinical screening tool to assess for potential colorectal cancer in those younger than age 50.
2. Engage primary care associations and providers for greater awareness of issues related to work-up of signs and symptoms of colorectal cancer.
3. Create awareness campaigns and strategies for consumers about the increase of colorectal cancer in people younger than age 50 and addressing stigma.
4. Examine patient preference in specific screening modalities for the 45-50-year-old-age group in the average-risk population.

Research minimally invasive strategies for preventive cancer screening, including analysis of blood, urine, and saliva (i.e., “liquid biopsies”); and examination of the oral and intestinal microbiome.

Strategies:

1. Define sensitivity and specificity based on patient needs and preferences.
2. Determine common quality and clinical thresholds and standards for emerging technologies.
3. Further engagement in ensuring patient accessibility.

Challenges

• Drugs like Pembrolizumab have been a breakthrough, with improved response and survival patterns compared to chemotherapy for patients with advanced mismatch repair-deficient/Microsatellite instable (dMMR/MSI-H) colorectal cancer, but have shown disappointing results in mismatch repair-proficient/Microsatellite stable (pMMR/MSS) colorectal cancer.

While there is considerable support and discussion about focusing on utilization of circulating tumor DNA (ctDNA) and novel therapies in the adjuvant setting, biomarker-selected studies for mCRC and treatment of oligometastatic disease (limited metastatic disease), there is a sense of frustration about the lack of advancement of immunotherapy in MSS mCRC patients. Making progress in immunotherapy for MSS patients is specifically noted as an unmet need.

• But perhaps the most perplexing issue is that colorectal cancer is actually a very individualized disease and “bucketing”’ into colon, rectal, MSS/MSI, etc. is not specific enough to truly provide the types of treatments and therapies that will overall improve colorectal cancer survival. 

We must confront the reality that treatment for colorectal cancer has only seen incremental improvements. A paradigm shift in thinking about treatment is needed. The real challenge and issue is that despite the advancements in treatment, not enough gains have been made to create any real change in overall survival for late-stage disease in several decades.

• In order to see individualized treatment progress, there is an analysis suggesting that a clinical trial system that enrolls patients at a higher rate produces treatment advances at a faster rate and corresponding improvements in cancer population outcomes

But there is a lot of work to do as we know that one in 20 adult patients with cancer enrolls in cancer clinical trials. Although barriers to trial participation have been the subject of frequent study, the rate of trial participation has not changed substantially over time.

Barriers to trial participation are structural, clinical, and attitudinal, and they differ according to demographic and socioeconomic factors.

Opportunities

• Oncology is at the vanguard of precision medicine: More than 160 oncology biomarkers were approved in 2019, and more than 90% of pivotal trials are against molecular targets.

Breakthrough therapies like Pembrolizumab have been game-changers for MSI-H patients; there is considerable excitement about how these findings might apply to MSS patients to improve treatment strategies.

• In President Biden’s fiscal year 2022-Presidential Budget Request, a proposal was included for $6.5 billion to create the Advanced Research Project Agency for Health (ARPA-H) to “develop breakthroughs to prevent, detect, and treat diseases like Alzheimer’s, diabetes, and cancer.”

The proposal seeks to address the fact that many bold, high-risk, high-reward ideas do not fit into the existing research structure either at the National Institutes of Health or within the work traditionally done by the private sector and instead create a dynamic organization centered around ensuring risk tolerance, urgency, nimbleness, and innovation. 

The goal is to speed the development and implementation of health breakthroughs—from the molecular to societal level—to serve all patients. 

Increase clinical trial enrollment, particularly for late-stage disease, microsatellite stable, and early-age onset patients.

Strategies:

1. Collaboration with industry partners, healthcare systems, and advocacy groups to amplify education campaigns.
2. Inclusion of social determinants of health equity and other cancer care delivery issues need to be addressed in design and outreach.
3. Deliberate inclusion of patient advocates and patients in building clinical trials.
4. Strengthen incentivization of patient recruitment into open trials across and throughout the U.S. and among institutions.

Increase biomarkers and molecular testing (localized versus metastatic).

Strategies:

1. Develop provider and patient education campaigns.
2. Strengthen alignment with quality and accreditation measures through National Comprehensive Cancer Network (NCCN) and Commission on Cancer.

Design trials that are individualized-sequence therapies.

Strategies:

• Integration of a multidisciplinary team for designs of next-generation trials.
• Better contextual understanding of tumor microenvironment and circulating tumor DNA (ctDNA) for trials.
• Implementation of clinical practice subgrouping by molecular phenotype and identifying ahead of time to preselect into clinical trials, RNA sequencing, and gene profiling. 
• Optimization of treatment strategies supported by preclinical science, specifically in:
  • Immunotherapy
  • Microbiome

Strengthen infrastructure design and development to advance treatment and clinical care.

Strategies:

1. Develop stronger tracking and review of outcomes for:
   • MSS Immunotherapy and combination strategies.
   • Informative failures.
   • Pooling of rare responders for MSS trials.
2. Strengthen pre-clinical/translational collaboration, creating better overall informative opportunities, identifying molecular targets, and more closely aligning clinical relevance.
3. Support national/standardized biobanking, particularly for early-age onset colorectal cancer:
   • Standard strategy and protocols for ascertainment.
   • Routine access to samples among institutions.
4. Establish an overall survival rate goal by 2023 with relevant and pertinent data.

Increase federal funding for colorectal cancer research to achieve previously listed objectives.

Strategies:

1. Create a Colorectal Cancer Research Program within the DOD CDMRP.
2. Ensure colorectal cancer is prioritized in the development and implementation of ARPA-H.
3. Engage the National Cancer Institute around key areas of opportunity for colorectal cancer research to provide more dedicated dollars to colorectal cancer treatment and prevention.

Currently, there are over 1.5 million colorectal cancer survivors in the United States. The five-year survival rate for people with colorectal cancer is 65%.

The term “survivorship” covers physical, psychological, social, and financial issues affecting patients during and after treatment. Our community of colorectal cancer survivors includes people with no disease, people who continue to receive treatment to reduce their risk, and those who manage a chronic but well-controlled disease with quality of life. It is incredibly important to recognize that colorectal cancer impacts families and entire communities of people.  

While there are wellness and medical guidelines for colorectal cancer patients after treatment is complete, gaps remain in who and how survivorship care is delivered. There is also variability from institution to institution about how survivorship care is delivered. 

The bottom line: Colorectal cancer survivors are often lost in the transition.

“An individual is considered a cancer survivor from the time of diagnosis, through the balance of his or her life. Family members, friends, and caregivers are also impacted by the survivorship experience and are therefore included in this definition.”

— National Cancer Institute Office of Cancer Survivorship (adapted from the National Coalition for Cancer Survivorship)

We are devoted to understanding the etiologies of cancer and improving treatments. Yet to truly succeed in our effort to find a cure, we must seek opportunities to expand cancer research efforts to include data on survivorship through clinical trials, large cohort studies, cancer registries, and national surveys. We need to understand the unique needs of colorectal cancer survivors in order to build programs that will meet their needs and improve overall quality of life for our community.  

You are alive, but are you suffering?

Challenges

• In late 2019, the American College of Surgeons Commission on Cancer (CoC) released Optimal Resources for Cancer Care: 2020 Standards for Cancer Program Accreditation. This was a big win for all survivors. ⁽⁴⁹⁾

This policy set a standard to require the cancer program’s cancer committee to oversee the development and implementation of a survivorship program directed at meeting the needs of cancer patients treated with curative intent. ⁽⁴⁹⁾ 

Today, there is a stronger focus on cancer survivorship and the needs of cancer patients; however, these interventions are often not reimbursed. Survivorship is an under-resourced area.

• To have a successful survivorship program, we must address the patient as a whole person. Easier said than done!

 Opportunities

• Based on the literature across all cancer types, we know treatment summaries (TS) and survivorship care plans (SCPs) are being implemented, but the data is mixed about their impact on improving patient outcomes. We know patients are riddled with challenges beyond treatment of their cancer. From mental health to nutrition, cancer patients face an avalanche of challenges, and there is a lot of thought and consideration on how to support patients in their survivorship journey.

How can we develop research efforts that include a holistic approach to survivorship?

• There is an opportunity to provide guidance and consensus on colorectal cancer survivorship standards. Part of the equation is delivery of care for virtual, telehealth, or in-person visits. 

Let’s have focused discussions on how to support the unique issues faced by young patients, late-stage patients, and those with specific tumor types, and/or receiving specific types of targeted therapies.

Colorectal cancer survivors are a diverse group facing long-term treatment side effects. Our research efforts should encourage and empower a proactive approach to support their overall health. From implementing survivorship care plans to unpacking the real-life experiences and quality of life of survivors, we can and should use this knowledge to inform future funding opportunities.

From surviving to thriving, you can’t help but think about recurrence. Approximately 30%–40% of patients develop recurrence following surgery, and 40%–50% of recurrences are apparent within the first few years after initial surgical resection.

Recurrent disease usually presents as distant metastasis in the liver or lungs or as locoregional recurrence in the pelvis or peritoneum.

The following are general statistics about the chance of recurrence:

• Stage I: <10%
• Stage II: 10%-15%
• Stage III: 25%-40%
• Stage IV: 50%-70% (after liver resection)

Challenges

• Numerous studies have shown the clinical utility of ctDNA, a noninvasive biomarker which can predict minimal residual disease (MRD), and how it can help us stratify colorectal cancer patients who are more likely to relapse.

However, what this means for guiding a patients’ treatment is still an active and important research question. The biggest questions are: Will patients treated with pre-surgical therapy, surgery, and post-surgical chemotherapy have additional treatments if there are signs of MRD? And how do we provide mental health support for those who do receive a positive ctDNA test?

Research advances in this area are especially important for our metastatic and early-age onset patients. Individuals ages 25 years old and younger with colon cancer appeared to be at higher risk for relapse and death than older adults, according to data published in Journal of the American College of Surgeons.

Opportunities

• ctDNA research is advancing rapidly, but are the study designs strong enough to change clinical practice? That’s what we are striving for. 

There is strong momentum to find clinical utility for these tests to help patients with a lower risk of recurrence avoid the side effects of additional treatment and those with a higher risk receive proactive care. 

There is great promise to use ctDNA tests with current standard monitoring guidelines in the early detection of recurrence, but it will only make a difference if patients have access to these advances.

• Our goal is for patients to live longer and enjoy their quality of life. To do this successfully, survivorship research efforts must elaborate and inform patients and their loved ones on the many issues relevant to long-term survival and risk of recurrence.

Development and research of survivorship care delivery intervention and approaches, which take into account the whole person—all of one’s health conditions and social conditions, not just one’s colorectal cancer.

Strategies:

1. Build consensus guidelines for Commission on Cancer survivorship recommendations for colorectal cancer survivorship taking into account the following key aspects:
   1. Integration of professional and evidence-based colorectal cancer survivorship guidelines in survivorship interventions;
   2. Improve ways to reduce suffering and mortality among survivors, and promoting return to life, work, and school;
   3. Focus on the needs of caregivers;
   4. Integrate evidence-based psychosocial services into standard of care;
   5. Enhance the education of survivors and all clinicians;
   6. Define quality measures for colorectal cancer survivorship care;
   7. Provide viable strategies that bridge care delivery with primary care and oncology care;
   8. Provide survivorship care that is sustainable, accessible, affordable, and equitable.
2. Build models of care and integrate what is published, established, and known about the specific needs of the differing “types” of colorectal cancer patients.
3. Include research advocates in designing and testing models of care delivery and approaches to risk stratification for colorectal cancer survivors that consider the whole person.
4. Implement and develop quality measures for survivorship care.
5. Increase the number of grants, dollar amounts, and grant mechanisms of PCORI, NCI, DOD, and CDC to fund colorectal cancer survivorship opportunities.

Increase the capacity of healthcare delivery systems, primary care, public health, and the health workforce to bridge care needs of colorectal cancer patients post-treatment.

Strategies:

1. Focus specific strategies to educate primary care providers and help bridge care from oncologists to primary care providers for longer-term management of colorectal cancer survivors’ needs and prevent recurrence.
2. Advocate with the CDC for supportive care and community-based services that must be purposefully developed for colorectal cancer survivors so they may continue their social, recreational, and vocational roles and functions in daily life.
3. Explore methods of care delivery for virtual, telehealth, in-person, or other delivery of care mechanisms to specifically support the needs of colorectal cancer patients.
4. Provide policy expertise to create sustainable patient navigation throughout the oncology care continuum, including into cancer survivorship.

Expand research efforts to improve and advance development of emerging and new technologies for early detection, screening, and prevention of recurrence.

Numerous studies have shown the clinical utility of ctDNA, a noninvasive biomarker which can predict minimal residual disease (MRD), and how it can help us stratify colorectal cancer patients who are more likely to relapse. However, what this means for guiding a patient’s treatment is still an active and important research question. 

The biggest questions are: Will patients treated with pre-surgical therapy, surgery, and post-surgical chemotherapy have additional treatments if there are signs of MRD? And how do we provide mental health support for those who do receive a positive ctDNA test?

Research advances in this area are especially important for our metastatic and early-age onset patients. Individuals ages 25 years old and younger with colon cancer appeared to be at higher risk for relapse and death than older adults, according to data published in Journal of the American College of Surgeons.

Strategies:

1. Assess the ability and extent for ctDNA tests to guide treatment decisions and monitor for MRD and recurrence in colorectal cancer.
2. Gather stronger data from patients to monitor recurrence, ctDNA, and the correlation with clinical outcomes.
3. Identify high-risk patients with remaining microscopic disease, so that treatment and follow-ups can be tailored accordingly.