The Colon Cancer Foundation had the opportunity to speak with Dr. Shahnaz Sultan, MD, MHSC, AGAF, about her research team’s findings that pandemic-related pre-procedure COVID-19 testing caused higher rates of endoscopy cancellations among patients from marginalized populations. A Professor of Medicine in the Division of Gastroenterology, Hepatology, and Nutrition and the Program Director for the Gastroenterology Fellowship Training Program at the University of Minnesota, Dr. Sultan’s research interests are focused on reducing colorectal cancer morbidity and mortality by improving adherence and quality of colonoscopy.

Q: What is the main takeaway you want people to understand from your research?

One of the most important things we want to emphasize is that colorectal cancer [CRC] is a very preventable cancer and there is a lot of high-quality evidence that shows that screening for CRC actually leads to a reduction in associated mortality. We really need to think about CRC screening along a continuum—whether you are doing stool-based testing or you’re getting a colonoscopy, it’s a multi-step process, and at every step, we need to be cognizant about reducing barriers and helping patients complete their CRC screening tests. Adding another step that patients have to complete prior to colonoscopy, such as pre-procedure SARS-CoV2 testing, in addition to completing their bowel prep, following dietary guidelines, finding transportation, and coming in to get a colonoscopy, really makes it that much more challenging. Pre-procedure testing serves as one more step and one more possible barrier in terms of getting people up-to-date with their screening. 

Q: As you were conducting your research, were there any findings that surprised you?

Our objective here was to understand the impact of pre-procedure COVID-19 testing—we wanted to see the magnitude of the impact and who was specifically affected by this additional requirement. When we looked at the canceled outpatient endoscopy procedures in our cohort from March 2021 to September 2021, we were surprised that the overall cancellation rate was so high in terms of getting people to complete their colonoscopy. Among the 574 cancellations, a little under 10% were due to pre-procedure COVID-19 testing requirements, and a good proportion of the remainder, about 51%, were patient-initiated cancellations. There were a lot of additional factors that were potentially holding people back from CRC screening. Additionally, we were surprised that pre-procedure testing was disproportionately affecting certain populations. Persons who self-identified as Black, American Indian, Alaskan Native, or Hispanic were more likely to have testing-related cancellations. 

Dr. Shahnaz Sultan

Q: Of the patients who canceled their colonoscopy, do we know if they went for an alternate form of testing for colorectal cancer, such as stool-based testing?

That’s an interesting question! We do not have that health data within our health system, but you bring up a good point. During the pandemic, a lot of other health systems were shifting gears from colonoscopy to stool-based testing and using programmatic efforts to directly reach out to patients to make sure they were getting some form of CRC screening. 

Q: Healthcare challenges, such as the COVID-19 pandemic, have demonstrated to significantly disrupt CRC screening procedures and participation, especially for medically underserved communities. What steps can be taken or what policies can be implemented in the future to support CRC screening participation and prevent significant disruptions to CRC screening?                                              

There is a lot of ongoing research to understand different barriers we can address or different interventions we can take to improve screening at the population level. We really need a multifaceted or multi-pronged approach to screening. We really need to think about interventions that not only focus on patients, but we also need to target providers, health systems, and community leaders, and think about national and federal policy decisions. I think there are a lot of opportunities to decrease barriers at different levels in terms of getting people to be more up-to-date with screening at a population level.

In terms of policy, one of the things that we have been able to fix recently is this loophole that existed in the past where if a test was done for screening purposes, but polyps were removed, then it was no longer counted as a screening test, and that incurred copayments and additional burdens on patients. I think that has been a real coup for us in the gastroenterology community and overall in terms of helping to support the care of our patients. Also, I think there are a lot of opportunities at the national level to support programmatic efforts to improve screening for populations that are underinsured or don’t have access to care, and I think we need to do more outreach and find ways to include health educators and patient navigators. We need to make sure we are educating patients about the importance of screening and helping address financial or logistical barriers that might serve as additional challenges for patients to overcome.

Continued on Page 2.

On June 17, 2022, the National Comprehensive Cancer Network (NCCN) held a policy summit to discuss cancer care in the workplace and building a 21st century workplace for patients, survivors, and caretakers.

One of the distinct portions of this summit was a panel on Patients, Survivors, and Caregivers in the Workplace: Contemporary Barriers and Solutions to Achieving Inclusive Workplaces. Panel moderator John Sweetenham, MD, FRCP, FACP, FASCO, Chair, NCCN Board of Directors, and Professor of Medicine, Associate Director of Clinical Affairs, UT Southwestern Simmons Comprehensive Cancer Center, noted that the disproportionate distribution of accommodations due to socioeconomic differences leads to inadequate care and suboptimal outcomes for certain populations.

Rebecca V. Nellis, MPP, Executive Director, Cancer and Careers, shared results from a 2021 Cancer and Careers/Harris Poll Survey, which found that for three-fourths of responders, work helped them cope and aided in their recovery. These statistics show us that we can work towards a healthier workplace environment for cancer patients  and subsequently influence their health outcomes. Lynn Zonakis, BA, BSN, Principal, Zonakis Consulting, former Managing Director of Health Strategy and Resources for Delta Air Lines, shared the strategies employed by Delta for combating the difficulties associated with a cancer diagnosis. “At all levels, I would say that people were very open to disclosure, and that was the vast norm, because in each work unit, at every level, there were multiple cancer survivors or survivorship in family members, so they understood that it was to their benefit to disclose.”

She did elaborate on the associated risks,  citing the example of pilots at risk of losing their jobs when disclosing mental health risks. This can be applied to a cancer diagnosis as well. “At a lot of organizations it can put you at risk. Some people will feel that their job could be vulnerable, and they won’t disclose it, so there’s no one size fits all,” she noted.

Workplace Flexibility for Patients and for Caregivers

Angela Mysliwiec, MD, Senior Medical Director, WellMed, touched on an important aspect of the support process: the caregivers. She spoke about a program at WellMed dedicated to assisting caregivers, who she explained are experiencing the same challenges as the person they’re caring for. “When it comes to work they need flexibility, they need to take care of themselves, they need their mental health cared for, and the organizations themselves who are often ill equipped to manage a person on staff with cancer can often be even more ill equipped to manage the caregiver,” Mysliwiec said.

Randy A. Jones, PhD, RN, FAAN, Professor, Associate Dean for Partner Development and Engagement, and Assistant Director of Community Outreach and Engagement at the University of Virginia, concurred with Mysliwiec. “Caregivers share the anxiety, they share the fatigue, along with some of the patients with cancer that they’re dealing with.” He also made a point about institutions having the resources to empower patients, especially since “people are more aware of these issues, you know people understand that there is an issue between how patients are getting benefits as well as how they may be navigating the system.”

Sweetenham and Nellis closed the panel by highlighting the importance of proactive planning instead of reactive planning. They recommended that organizations should implement workplace flexibility that should be communicated upfront to new employees, and then practice it on a regular basis instead of making adjustments and assumptions as events occur.

Employer Policies Play a Big Role 

Joanna Fawzy Morales, Esq., Chief Executive Officer, Triage Cancer, spoke to the audience about The Policy Landscape to Support Patients, Survivors, and Caregivers at Work. Morales pointed out that employment can be a contributor to financial toxicity in the form of lost wages, employee benefits, and more. She further elaborated on a point that Nellis had made about battling assumptions, saying that “Employers have assumptions about their employees who’ve been diagnosed with cancer and their ability to do their jobs. Health care professionals make a whole lot of assumptions about their patients and whether or not they want to work or they can work.”

Explaining the current and suggested employment rights and accommodations, Morales said that they play a big role in helping patients make educated decisions on next actions. While there is a significant lack of awareness of protections available through the law, there are several gaps that need to be bridged. “There are many opportunities to close those gaps to improve the quality of life of patients and their families and mitigate the financial toxicity of a cancer diagnosis,” she added. She concluded her talk by emphasizing the need to educate employers, health care professionals, and the cancer community.

From informing the employer to the employee to equitable care for patients and their caregivers, this policy summit discussed various aspects of cancer in the workplace, and how we can improve the experience for those involved.

Juhi Patel is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

Image credit: Mohamed Hassan, Pixabay

 

CCCF Research

At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, several research studies were presented that shared a targeted approach to colorectal cancer (CRC) treatment that can ensure efficacy and reduction of side effects. The infographic below highlights those studies and their key findings.

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In May 2021, the US Preventive Services Task Force (USPSTF) revised the colorectal cancer (CRC) screening age for average-risk adults to 45 years. However, stakeholders are concerned about the lack of awareness, access, and motivation among the younger age group to get screened. Now, a new research study has found that the prevalence of CRC screening remained lowest for individuals ages 50 to 54 years old and young adults (age<50) experienced smaller increases in screening prevalence over time, regardless of race, ethnicity, education, income, and insurance coverage. 

An investigation using population-based data from the National Health Interview Survey (NHIS), an annual, cross-sectional survey of the U.S. population conducted by the National Center for Health Statistics at the U.S. Centers for Disease Control and Prevention, studied CRC screening participation using surveys from multiple years. A sample of 80,220 participants ages 50 to 75 years old was analyzed for CRC screening participation. For each survey year, the prevalence of CRC screening was estimated for age, race, ethnicity, educational attainment, family income, and health insurance.

Racial, ethnic, and socioeconomic disparities influence screening rates. Despite the prevalence of CRC screening increasing from 36.7% in 2000 to 66.1% in 2018, screening prevalence was observed to be the lowest for:

  • Participants ages 50 to 54 years old
  • Hispanic populations (56.5%)
  • Asian populations (57.1%)
  • Participants with less than a high school degree (53.6%)
  • Participants from low-income families (56.6%)
  • Participants without insurance (39.7%) 

This may be the result of a lack of concern for cancer and cancer screening among younger adults and their healthcare providers, limited access to healthcare, absence of or limited insurance coverage, and other priorities for young adults, such as work and family. Disparities in screening rates can potentially extend to adults ages 45 to 49 as the new USPSTF recommendations are implemented. Multilevel barriers, such as patient-, provider-, and system-level factors, impact the completion of CRC screening for young adults (age<50), creating disparities and inequities in CRC screening. The administration of new CRC screening guidelines must acknowledge and account for multilevel disparities in screening programs to ensure all populations have equal access to CRC screening and benefit from CRC screening, especially newly eligible adults ages 45 to 49 years old. 

The benefits and outcomes of the updated USPSTF guidelines to extend CRC screening to ages 45 to 49 years old have been debated by clinicians and researchers. Concerns about the updated guidelines include redirecting endoscopic resources away from higher-risk and older patients, resulting in a more significant exacerbation of health disparities. Another criticism is that adults ages 45 to 49 years old who participate in screening may be less likely to belong to groups at higher CRC risk. 

One benefit of expanding CRC screening to the 45-49 age group is to increase the screening participation rate among older populations. Awareness of CRC screening may also increase, resulting in newly eligible adults having more time to schedule their first screening test. However, the impact of screening among those in the 45-49 age group on disparities, benefits, and participation of older adults may take several years to be fully recognized and understood, as the USPSTF’s effect on insurance coverage only occur in mid-2022.

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

Medically underserved communities experience significant health care inequities, including preventive screening for colorectal cancer (CRC) and CRC-related morbidity and mortality. Multilevel barriers to CRC screening and subsequent follow-up create disparities and inequities in individual outcomes. Pandemic-related pre-procedure COVID-19 testing has been shown to cause higher rates of endoscopy cancellations among patients from marginalized populations. This, in addition to financial concerns, patient mistrust, lack of access to specialists and colonoscopy services are just some of the barriers to completion of CRC screening and follow-up procedures. 

CRC Screening Disparities: What’s the Solution?

The fecal immunochemical test (FIT) is one of the most widely used CRC screening methods globally and is an affordable screening tool for studying large populations. FIT detects hidden blood in stool, which can potentially be an early sign of cancer, and is an affordable home-health test with an overall 95% diagnostic accuracy for CRC. However, to be an effective screening tool, each step of the multi-step screening process must be completed: a diagnostic colonoscopy must follow a positive FIT test. Failure to complete the screening process is associated with higher rates of CRC mortality. 

While patient navigation helps with follow-up after a positive FIT test, only one-third of patients complete colonoscopy. Proactive, organized CRC screening involving centralized tracking, reminders, alerts for providers, and culturally competent and tailored messaging for patients are more effective for improving screening rates for White and African American patients. Such tactics have also reduced the differences in screening rates and cancer-specific mortality between White and African American patients. 

The COVID-19 pandemic has disproportionately impacted medically-underserved communities. African American, American Indian/Alaska Natives, and Hispanic populations have been particularly hard hit. COVID-19 testing requirements prior to endoscopy have disproportionately affected medically-underserved communities. 

While COVID-19 testing was a requirement earlier in the pandemic, the American Gastroenterological Association updated its guidelines as our understanding of viral transmission improved, vaccines became available, and viral transmission during endoscopy was found to be minimal. However, multiple institutions have continued to require pre-procedure COVID-19 testing prior to medical procedure—including endoscopy—which has led to high rates of endoscopy cancellations among individuals from marginalized populations. Pre-procedure testing may have introduced an additional barrier to care and increased existing disparities in health care and health outcomes. 

Recommendations for Eliminating Screening Barriers

Researchers have recommended the following strategies to reduce the impact of disparities due to COVID-19 testing:

  • Mailing SARS-CoV2 testing kits to endoscopy patients several weeks pre-procedure
  • Offering rapid testing to patients on the day of the procedure
  • Offering an opt-out option for testing due to hardships, such as the inability to schedule testing due to work schedules, difficulties finding transportation, or the need for childcare

Multilevel barriers to CRC screening and appropriate follow-up after screening create disparities and inequities in health care outcomes. Healthcare systems must collaborate with healthcare providers, community leaders, and social service representatives to improve access to care and guarantee equitable health care for all.  

 

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

Jamie Crespo lives in Seattle, Washington and is a Colon Cancer Foundation (CCF) Champion. She was introduced to CCF through the New York City marathon when she registered to run for our charity in 2020. When looking through charities, she found that CCF’s mission and cause was relevant to her personal experience with her family. Due to the COVID-19 pandemic, she ran the marathon in 2021.

In 2017, Jamie’s parents who were both in their 60s had never undergone a screening colonoscopy. In the absence of a family history of colon cancer, they did not even consider scheduling one. However, her father started losing a significant amount of weight and seemed very pale. When Jamie persuaded him to see a doctor, they discovered he had internal bleeding. After running some tests, the doctors found a mass in his colon. Following a colectomy, he was diagnosed with stage 3B colon cancer. Jamie’s father started chemotherapy in the fall of 2017 and is, fortunately, in remission!

In the beginning of the same year, Jamie’s mother was to receive a check-up but it was delayed to the fall due to her father’s diagnosis and subsequent treatment. Unfortunately, when her mother went through a screening colonoscopy, she was diagnosed with stage 1 colon cancer. Thankfully, she was able to undergo a laparoscopic colectomy, in time, and remains in remission.

With no known history of colon cancer in her family, Jamie emphasizes that everyone should initiate their screening at the recommended age of 45 years. She promotes preventative care knowing that typically, individuals who present with symptoms may be diagnosed at a more advanced stage when the disease is less treatable. Ever since her parents’ diagnoses, Jamie posts regularly on social media and raises money for the CCF. She is a member of the Club Seattle Runners Division and posted photos of her run to promote colorectal cancer awareness as well as relay her personal story of colorectal cancer. 

You can find Jamie on Instagram: @jamielynette

Kenadi Kaewmanaprasert is a Colon Cancer Prevention Intern with the Colon Cancer Foundation. 

The American Gastroenterological Association (AGA) has developed 8 position statementssolutions to eliminate colorectal cancer (CRC) screening barriers and reduce CRC burden. Evidence supports the existence of disparities in CRC screening: individuals with low income and lack of access to insurance coverage are disproportionately affected. Cost-sharing for preventive screening, in the form of deductibles and copayments, can be a financial barrier for some individuals. CRC screening programs and policies should cover all the steps following screening because each element is essential to the effectiveness of a screening program. Furthermore, these factors should not be subject to cost-sharing. Uniform, equitable delivery of screening programs will not only improve adherence and participation in CRC screening but also eliminate health disparities and reduce the burden of CRC in the United States. 

The following infographic details AGA’s approach:

The position statements have been published in Gastroenterology.

 

Photo credit: Clarissa Watson on Unsplash

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

Justin Adler is a Colon Cancer Foundation (CCF) Champion who lives in New York City. He works for a small SaaS (Software as a Service) company leading their strategic finance team. In addition to being involved with CCF, Justin coaches a football team and is a member of the Big Brothers Big Sisters of New York where he mentors a 9-year-old boy. He joined CCF in the beginning of 2022 as he hoped to be involved with something more personal.

CCF Champions started off as a young leadership council of the board—it has now evolved into a team of individuals with a personal or familial impact of colorectal cancer. The team meets on a monthly basis to discuss how best to support CCF’s mission of raising awareness around colorectal cancer from a board perspective, including leading and participating in the Foundation’s events.

One such event was  the annual Colon Cancer Challenge 5K Run/Walk during the Colorectal Cancer Awareness Month in March. Each Champion led their own team and fundraised individually. As a team, they also create social media campaigns. Recently, they partnered with DuClaw Brewing on their “Give A Crap” campaign to fundraise and share each champion’s personal story around colorectal cancer.

Justin was 8 years old when his mother passed away from colon cancer. Seeing at a young age how the disease affected his mom and their family, he is very keen to spread the word on the importance of early detection. Because his mother was not screened prior to her diagnosis, his main goal is to push the message of colorectal cancer screening. Justin notices that individuals without a family history of colorectal cancer are not as motivated to schedule a colonoscopy. They sometimes push it off until they are required to receive one, which could potentially be deadly for some. He emphasizes building a level of comfort around the topic, citing the “Give A Crap” challenge as an example, where they spoke openly about the elephant in the room.

Justin and the rest of the CCF Champions are always on a lookout for opportunities to partner with and help further colorectal cancer research and treatment through fundraisers and also spreading awareness.

 

Kenadi Kaewmanaprasert  is a Colon Cancer Prevention Intern with the Colon Cancer Foundation.

There is little known about the connection between various factors (such as environmental quality index, unmet needs, cancer survivorship, etc.) and the outcomes of patients affected by colorectal cancer (CRC). Studying the trends and associations around the onset and progression of CRC is integral to educating people on risk reduction. Additionally, using a disparity lens can aid decision-making processes and allow providers to target high-risk populations who may be in need of greater assistance and care. 

Several such studies were presented at the 2022 annual meeting of the American Society of Clinical Oncology. For example, Suleyman Yasin Goksu and team studied the association of young-onset CRC with the national level Environmental Quality Index (EQI). Their greatest finding? YOCRC can be linked to lower environmental quality. Additionally, Megan E. Delisle and team identified the association between unmet needs (in the physical, emotional, and practical sense) and survivors’ utilization of emergency services in the first three years following treatment. They found that a greater amount of unmet needs could be linked to higher utilization of emergency services–which is an issue that can be resolved through preventative measures. Both these studies reach important conclusions regarding how we draw patterns from disease. 

Here are some other studies from ASCO that dived into disparities and early-age onset CRC (EAO-CRC) outcomes:

  1. Disparity of treatment-related adverse events and outcome in patients with early-onset metastatic colorectal cancer (mCRC). With the marked rise of early-onset metastatic CRC (mCRC), there is a gap in diagnosis and adverse events related to treatment. Patient outcomes have not been conclusively studied, so Lingbin Meng and team reviewed the potential age-related disparity and its causes. Using individual patient data from three clinical trials in Project Data Sphere, patients were categorized into three age groups and sorted by adverse events. Patients younger than 50 had shorter median overall survival, higher incidence of toxicity (abdominal pain, severe anemia, and nausea/vomiting), but lower incidence of severe diarrhea, neutropenia, and fatigue. This group had the earliest onset of these adverse events and was associated with worse overall survival. Some of these disparities may be explained by distinct genetic profiles, but overall, patients with early-onset mCRC had worse outcomes and endured greater overall treatment-related adverse events. This study provides a basis for developing a personalized treatment plan when selecting patients for chemotherapy, providing counseling, and monitoring adverse events.
  2. Modifiable and non-modifiable risk factors associated with early-onset colorectal cancer: Analysis of the National Health Interview Survey. Risk factors for EAO-CRC are largely understudied, while on the other hand, there is a rapid increase in incidence. Hyeun Ah Kang and Yahan Zhang of The University of Texas at Austin studied modifiable and non-modifiable risk factors associated with the rise. Their cross sectional study analyzed data from the 2004-2018 National Health Interview Survey (NHIS). Individuals between the ages of 18 and 49 with a history of CRC diagnosis at the time of the interview were compared with their non-cancer counterparts. Additionally, the researchers also compared their nonage-related characteristics to those with late-onset CRC, meaning after 50. One hundred and fifty six patients with EAO-CRC were identified. Results from the comparisons showed that greater odds of EAO-CRC were associated with older age, living in the Midwest, and history of alcohol consumption. Lower odds were associated with Hispanic or Asian race and a lifestyle of vigorous physical activity. This study points to both modifiable and non-modifiable characteristics of EAO-CRC risk. Further studies can help identify the associated risk in-depth.
  3. Racial disparities in receipt of guideline-concordant care for early-onset colorectal cancer in the U.S. Black patients diagnosed with EAO-CRC have worse survival than their white counterparts, even in lieu of early-stage disease. Leticia M. Nogueira and team studied these racial disparities, with specific focus on guidance-concordant cancer care.The study included newly diagnosed non-Hispanic black and white individuals  between the ages of 20 and 49. Demographics, comorbidities, and insurance coverage were added to multivariable models to predict their contribution in the disparities with quality measures. Out of the 84,728 colon and 62,483 rectal cancer patients, 20.8% and 14.5%, respectively, were black. They were less likely to receive guideline-concordant care than white patients, which was primarily driven by insurance coverage rather than demographics or comorbidities. Overall, black patients received worse and less timely care than their white peers. Health insurance, a modifiable factor, was identified as the largest contributor to this gap. This study suggests that access to care can significantly influence EAO-CRC outcomes.
  4. Racial parity in rectal cancer treatment and outcomes within an integrated healthcare system. Hyunjee V. Kwak and team also looked at the survival outcomes of patients in the context of their race. They conducted a retrospective study of patients at the Kaiser Permanente Northern California health system, who were treated between 2010-2019. The study included over 3,500 patients diagnosed with rectal adenocarcinoma. Using self-reported race information, various analyses evaluated differences in race, age, stage of diagnosis, treatment, and overall survival. There was a greater proportion of Black patients with localized disease, who also had the longest overall survival. Hispanic patients were more likely to be male, younger, and have a shorter overall survival. These results show a gap in survival outcomes for patients treated at a large integrated healthcare system, where access to care is roughly equal. This calls for an improvement in outreach and screening, as well as awareness in these communities.
  5. Trends and disparities in the treatment of older adults with colon cancer. Half of the patients diagnosed with colon cancer are aged above 70, yet there is a huge gap in treatment for this population. Most are undertreated, perhaps due to age-related biases. Philip Q. Ding and team looked at age-related disparities in the realm of CRC care. Their retrospective, population-based study of adults diagnosed with CRC between 2010 and 2018 in Alberta, Canada included more than 10,000 patients, 48% of whom were over 70 years old. Upon further examination, it was found that older age correlated with more comorbidities and less advanced disease. Despite this, there was no statistically significant correlation between age and treatment status. As compared to the younger group, the odds of receiving surgery and systemic therapy were three and five times lower (respectively) among older patients. These two interventions continue to improve the outcomes of colon cancer in old and young patients alike, but the rates of treatment were lower in older patients and with minimal change over time. This study highlights a disparity in CRC care within the geriatric population.

Identifying these trends and disparities is just one step towards improved CRC care. It empowers patients to identify their personal risk and also gives their provider another factor to consider for treatment and prognosis. Understanding these correlations may be the next step in eliminating the gap in care for many populations.

 

Juhi Patel is a Colorectal Cancer Prevention Intern at the Colon Cancer Foundation.

Locally advanced rectal cancer may involve multistep neoadjuvant therapy to shrink the tumor before the main treatment, which is often surgery. Although this approach results in a complete pathological response in up to 25% of patients, it involves the risk of complications and toxic effects, including bowel, urinary, and sexual dysfunction; infertility; and altered quality of life in a significant number of patients. A new study, published in the New England Journal of Medicine, has found that patients with mismatch repair-deficient, locally advanced rectal cancer can be effectively treated with neoadjuvant programmed death-1 (PD-1) blockade.  

Approximately 5-10% of rectal adenocarcinomas are attributed to mismatch-repair deficiency, and this subset of tumors respond poorly to standard chemotherapy treatments. Immune checkpoint blockade could be an effective treatment option for this subset of patients. PD-1 elicits an immune checkpoint response of T-cells, allowing tumor cells to bypass the immune system defense, as well as resist the effects of chemotherapy. To test this hypothesis, researchers at Memorial Sloan Kettering Cancer Center and Yale University School of Medicine conducted a phase 2 investigation to analyze the overall response and frequency of sustained clinical complete response to neoadjuvant treatment with a PD-1 inhibitor, dostarlimab. 

PD-1 Blockade Eliminated Rectal Tumors

Of the sixteen patients enrolled in the study, twelve were enrolled for more than six months and completed nine cycles of dostarlimab. The resulting clinical complete response was measured by a combination of rectal MRI, visual endoscopic inspection, and digital rectal examination in twelve patients who had at least six months of follow-up. Endoscopic biopsies were performed at baseline and during visual inspection of tumor response at six weeks, three months, and 6 months, and then every four months thereafter. Serial FDG-PET scans to evaluate tumor eradication presented similar results to that seen with pathological examination and genomic analysis of the evolution of tumor eradication. 

The elimination of tumors after six months of therapy with PD-1 blockade allowed Dr. Cercek and her team to be able to omit both chemoradiotherapy and surgery and to move forward with observation alone. Single-agent dostarlimab was significantly influential in treating mismatch repair-deficient, locally advanced rectal cancer. It provided a clinical complete response in all 12 patients who completed treatment to date. 

Surgery and radiation can permanently impact fertility, sexual health, and bowel and bladder function. With the rise in incidence of rectal cancer among young patients of child-bearing age, anti-PD-1 antibodies can be a good alternative to chemoradiotherapy and surgery and may specifically benefit this cohort of patients. Dostarlimab promotes a refined approach toward treatment that can significantly improve the quality of life of patients, especially younger patients who may not yet have started a family. These findings also encourage the potential for using PD-1 inhibitors in the treatment of other mismatch repair-deficient tumors, such as localized pancreatic, gastric, and prostate cancers.

 

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