It is finally here! The U.S. Preventive Services Task Force (USPSTF)’s final recommendation has lowered the colorectal cancer (CRC) screening age for average-risk adults from 50 to 45 years. This long-awaited final recommendation came a little over six months after the draft recommendation was released in October last year.

This is a B grade recommendation, meaning that there is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Screening for 50–75-year-old adults remains an A grade recommendation, meaning USPSTF believes there is high certainty of substantial net benefit with screening that age group. The recommendations have also been published in JAMA.

Lowering the screening age from 50 to 45 years is great news for the CRC community because it will significantly influence the earlier diagnosis of CRC among the younger age group. To bring this into perspective, a recent paper in JAMA Network Openprojected that by 2040, CRC will be the second most common cancer in the 20-49 age group and it will be the leading cause of cancer-related deaths in that age group.

Ana Acuna-Villaorduna, MD, Department of Medical Oncology at Montefiore Health System, believes that the lowering of screening age could halt the alarming rise in early-age onset CRC, particularly among racial and ethnic minority populations. “Considering US-based population projections that foresee a continuous increase in racial/ethnic minorities and have higher frequencies and worse clinical courses of colorectal cancer among young patients, it is necessary to adopt a screening strategy aimed to halt this alarming trend,” Dr. Acuna-Villaorduna wrote in an email.

She believes that general practitioners and family physicians will be strategic players in implementing the new measures by educating patients in the community, along with gastroenterologists and medical oncologists. However, uptake of these recommendations by the primary care clinical community may be slow, depending on the messaging strategies that are utilized.

“As usual, it will take a while to get the message out,” Zuri A. Murrell, MD, FASCRS, Chair, Cancer Committee, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, told the Colon Cancer Foundation. “Having a media blitz will be helpful. Organizations like the American Cancer Society and the Colon Cancer Foundation will be the main people who will not only get the word out to providers, but to the community as well,” he added.

Dr. Acuna-Villaorduna thinks that the USPSTF recommendation will finally build a consensus across the various medical societies that have disparate CRC screening recommendations. She believes that some physicians may already have been screening average-risk adults at 45 years, so guideline uptake may be faster.

What Else Will Influence Uptake of the Guidance?

Another important question is whether our health care system has the capacity to onboard the 20-21 million adults in the 45-49 age group who are now eligible to get screened. While colonoscopy remains the gold standard, other screening options, including stool-based testing, could be used to conduct the initial screen. Whitney Jones, MD, Founder, Colon Cancer Prevention project, agrees. “While we cannot conduct colonoscopy in all the new population, we can definitely send them stool-based testing kits. That’s what health systems should focus on,” he said while speaking with the Colon Cancer Foundation.

The other issue is insurance coverage for CRC screening as a preventive care service for the 45-49 age group and making sure payers—both government and private—are aware of the updated guidelines and are integrating these within their policy.

Currently, most insurers will cover the cost of a preventive screening test for those 50 years or older, but the enrollee may have to share the cost of a diagnostic screening test if a polyp or tumor is found.

If historical trends are any indication, insurance coverage of colonoscopy will significantly influence increased screening in the younger age group. Evidence for this is stark in the Medicare population: colonoscopy rates jumped from 20% in 2000 to 61% in 2018 among those 50 and older after Medicare started covering colonoscopy screening for all beneficiaries in 2001.

Once the updated recommendations of CRC screening age are implemented, Dr. Murrell is hopeful that insurance companies will listen and hopefully start covering the cost of the simple preventive procedure. He also raised an important point about eliminating fear from the mind of the younger community. “I have coined a slogan that I always share with my patients: ‘You shouldn’t die from fear you shouldn’t die from embarrassment.’ This will be the first step in helping and encouraging people to get a colonoscopy,” he added.

Advancements in screening, diagnosis and treatment of colorectal cancer have come a long way in the past two decades, but the need to continue to spread awareness of the disease among young people and continued industry-wide collaboration and investment is necessary to offset the growth in incidence under the age of 50. Those were among the key topics of the 7th annual Early-Age Onset Colorectal Cancer Summit.

The three-day conference, which was held online in a virtual format because of ongoing Covid-19 precautions, concluded on Sunday, May 16. It was organized by the Colon Cancer Foundation, a New York-based 501(c)3 non-profit organization dedicated to reducing colorectal cancer incidence and death. (Presentations from all three days can be viewed online andCME and MOC credit will be available for 30 days.)

At the outset of the third day of the summit, a panel of distinguished experts addressed the case study of a 28-year-old colon cancer patient from a broad-spectrum approach, offering input on patient perspective, nurse navigation, genetics, medical oncology and new therapeutics, surgery, financial burden/toxicity, radiation oncology, psychological needs, pediatrics and palliative care.

The female patient in the opening panel discussion was described as presenting with a multi-year history of chronic constipation for which she took laxatives. Six months prior to visiting an emergency room, she started experiencing a change in symptoms with tenesmus, rectal pain, bowel urgency with intermittent rectal pressure deep in the pelvic region that worsened with prolonged standing.

At the ER, she had an abdominal/pelvic CT scan that showed presence of a moderate amount of stool in the ascending colon, a thick-walled appearance of the rectum about 6cm from the anal verge down to the anal canal/anorectal junction. Those abnormal symptoms prompted a colonoscopy that showed a non-circumferential mass in the distal rectum to the anal verge. A biopsy returned as invasive moderately differentiated adenocarcinoma.

The patient was described as healthy with a BMI of 22 and had no other medical history and was not taking any medications. The only colorectal family history she had was that her father had several polyps removed after the age of 50.

1. Spreading the message about early-age onset colorectal cancer to young people is crucial so symptoms aren’t overlooked or disregarded.

Often young people ignore or miscategorize their symptoms or are too busy to visit their doctor or aren’t concerned because of a lack of family history or because they lack general awareness about colorectal cancer. In some situations, the initial symptoms have disregarded after being attributed to hemorrhoids or other common benign conditions.

“About 70 to 80 percent of our patients that have colon or rectal cancer do not have a family history of the disease, even if someone in the family had a colonscopy and had polyps removed. I always think it’s important to get pathology of the polyps of family members and also to make sure the parents and siblings of the patients have had colonoscopies.”
Zsofia Stadler, MD, Associate Professor, Clinical Director, Clinical Genetics Service, Memorial Sloan Kettering Cancer Center

“It typically takes about 270 days from the onset of symptoms to diagnosis in young patients because. Most of the time, their symptoms are dismissed as something benign like an upset GI tract that everyone has. As a result, they usually are not given the medical attention that they deserve.”
Manju George, MVSc, PhD, Scientific Director, Paltown Development Foundation.

2. The top priority with younger colorectal cancer patients is curing the cancer, but there other quality-of-life issues are critical.

An ensuing pelvic MRI confirms a tumor that arises from the right lateral wall at the level of the levator. The distal edge of the tumor is at 2cm from the anal verge and the tumor abuts the internal sphincter. It is at clinic stage III (mrT3aN1b). In this kind of case with a distal tumor, sphincter preservation is very unlikely, and local recurrence is higher for distal tumors than for proximal tumors.

All three modalities of treatment would likely be considered for this patient: chemotherapy because she’s at risk of distant spread, radiation for local control and the distal location and an abdominal perineal resection surgery to maximize disease control. But quality of life priorities that must be considered include maintaining fertility and avoiding a permanent colostomy.

“This is a great case because it’s so illustrative of so many issues, but it’s also a terrible case because when you see cases like this you know the discussions are going to be very difficult and there is no perfect solution and compromises are going to need to be made.”

Harvey Mamon, MD, PhD, Associate Professor, Radiation Oncology, Harvard Medical School, Director of GI Radiation Oncology, Brigham And Women’s Hospital, Chief, Division of Gastrointestinal Radiation Oncology

3. Fertility preservation options should be discussed as soon as possible after diagnosis.

When a patient has more time to consider egg harvesting or freezing sperm, they can consider it and accomplish it without significantly delaying the onset of their cancer treatments.

“We do want to see these patients as soon as possible, not only because it gives them more options and more time for options. When we talk to patients about fertility preservation, we want them to take a more bird’s-eye view instead of just whether or not they want to freeze their eggs or sperm. They also have to answer questions about whether they can carry a pregnancy after radiation treatment or do genetic testing in the case of a genetic mutation.”

— Terri L. Woodard, MD, Associate Professor Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center

4. Early psychological and social support is necessary for young colorectal cancer patients.

Early referral for a psycho/social assessment is especially important for adolescent and young adult colorectal patients who will have to transition to a permanent colostomy. Reducing the anxiety and depression related to the necessary changes in daily life, family, jobs, social interaction and more

“As clinical social workers and oncology social workers, the No. 1 goal is making sure we meet that patient where they are at and get a sense of who they are, who their support is, if they have any barriers to care based on their socioeconomic status and understanding workplace issues.”

Krista Nelson, LCSW OSW-C BCD FAOS, President of the Association of Community Cancer Centers

“In my experience working with younger patients, it is such an enormous adjustment and really impacts their quality of life and body image and conversation with family and friends and dating and so many different layers of life. Providing support and psychotherapy around anticipating the adjustment and then making the adjustment to life with a colostomy is hugely important.”

Hadley Maya, MSW, LCSW, Center for Young Onset Colorectal Cancer Clinical Social Worker, Memorial Sloan Kettering Cancer Center

For additional topics addressed in Session IV, view the full presentation online.

Other highlights of Day 3 included breakout sessions about “Understanding and Addressing Disparities in Early-Age Onset Colorectal Cancer” and “Integrating Music Therapy in Cancer” followed by the conference-concluding Session V, a panel discussion titled “How Did This Happen? Investigating the Causes of Early Onset Colorectal Cancers.”

Moderated by Stephen Gruber, M.D., that session addressed the future of early-age onset colorectal cancer that included discussions about mining electronic health record data and integration with large-scale genomic analyses, the international colorectal pooling project, how microbiome interactions contribute to the rise of early-age onset colorectal cancer and how diet, smoking and obesity, as well as maternal obesity and gestation growth.

Gruber stressed the need for continued collaboration and specific investment to help further the fight against the increasing trend of colorectal cancer in younger people.

“This is not a rare disease anymore but at each center there’s a relatively small number of cases,” Cynthia Sears, MD, Professor, Johns Hopkins University School of Medicine. “.  If I can dream, we would create a network, a center of communication and a way to contribute, maybe similar to the TCGA Data Portal – a big data set and some parallel sample collection that would allow, hopefully, the exposure questions to really be pursued. I do think it’s the epidemiology, exposures and sufficient population that we need and it’s hard to get it at one institution.”

In closing remarks, Cindy Borassi, president of the Colon Cancer Foundation, thanked the nearly 300 conference attendees and 50 medical professionals who participated in the seventh annual Early-Age Onset Colorectal Cancer Summit. Sponsors for the summit included Quest Diagnostics, Walgreens, Exact Sciences, Colon Cancer Coalition, Colon Cancer Prevention Project, Taiho Oncology, Daiichi-Sankyo, BRACCO Group, DuClaw Brewing Co. and Squatty Potty

“We invite you to join the discussion, collaborate with thousands of health professionals who are interested in solving the early-age onset colorectal cancer issue,” Borassi said. “I would encourage everyone to tell others to watch the videos on the platform, especially primary care physicians as we all know they are a bit part of the key to solving this issue.”

Day 2 Highlights

Day 2 included the Keynote Address of Stephen Gruber, MD, and Session II, a panel discussion called “The Dimensions of the EAO-CRC Problem: Do We Have Accurate, Regular, Up to Date Measurement of Key Metrics Describing the Early Age Onset Colorectal Cancer Public Health Crisis.” That session included an update about the rising early-onset CRC trends and racial disparities, the impact of COVID-19 on CRC screening and an under-19 incidence and mortality report. Session III was a panel discussion that explored “Risk Assessment/Family History Ascertainment” and included discussions about CRC screening guidelines, increased access to genetic testing and patient access to appropriate care.

Day 1 Highlights

On Day 1, Dr. Whitney Jones, MD, founder of the Colon Cancer Prevention Project, moderated an Session I, a panel discussion about “Improving Earliest Possible Diagnosis and Treatment through Timely Recognition of the Symptoms and Signs of Sporadic Young Adult CRC” with additional topics related to the echo chamber of cyclical discussions, incidence rates and mortality rates by 2040, primary care in improving early diagnosis and a colorectal cancer patient testimonial case study.

To watch any of the presentations, register for the Early Age Onset Colorectal Cancer Summit and access the recorded programs.

Suggesting a call to action for a more comprehensive and collaborative effort against the rise of colorectal cancer in patients under 40, Stephen B. Gruber, MD, PhD, MPH, presented the Keynote Address of the seventh annual Early-Age Onset Colorectal Cancer Summit on Saturday, May 15.

Gruber’s lecture was the highlight of Day 2 of the three-day conference, which is being held online in a virtual format because of ongoing Covid-19 precautions. It is organized by the Colon Cancer Foundation, a New York-based 501(c)3 non-profit organization dedicated to reducing colorectal cancer incidence and death.

Gruber, the vice president of the City of Hope National Medical Center in Duarte, Calif., began his presentation with the story of a young patient, who at age 28, was diagnosed with colon cancer that led to metastatic disease and ultimately her death despite having had no known risk factors for colon cancer.

Despite all of the best efforts to understand how she developed colon cancer at such a young age, it wasn’t possible to trace her disease back to any specific genetic or environmental causes. Unfortunately, that’s the status quo for early age onset colorectal cancer as of 2021, Dr. Gruber said. Although overall incidence rates of colorectal cancer have declined over the past 30 to 40 years, the incidence rate has increased substantially since the mid-1990s in adolescents and young adults.

According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related deaths in men and in women in the U.S., and the second most common cause of cancer deaths when men and women are combined. It’s expected to cause about 52,980 deaths in the U.S. in 2021. The overarching etiology of the disease has not been established; there is no definitive cause of colorectal cancer.

From 2013 to 2017, incidence rates dropped by about 1 percent each year. But that downward trend is mostly in older adults and masks rising incidence among younger adults since at least the mid-1990s. From 2012 through 2016, it increased every year by 2 percent in people younger than 50 and 1 percent in people 50 to 64.

“The reasons remain unknown. We don’t know why cancer is increasing in this group,” Dr. Gruber said. “As we think about all of the possible explanations, including Western-style diet, obesity, physical inactivity, antibiotic use, especially in the early life period of time, it’s not clear why this increase incidence and epidemic of early onset colorectal cancer is being observed.”

Dr. Gruber presented regional findings from his experience and research at the City of Hope National Medical Center in Duarte, Calif., work from the USC Norris Comprehensive Cancer Center in Los Angeles, as well as numerous other national and international studies to help understand some of the reasons that might be contributing as to why the disease is increasing in younger people.

He presented papers that outlined risk factors classified into systems and institutions, including screening policies within healthcare systems that contribute to early diagnosis or fail to diagnose. He questioned how microbiome changes within family environments could impact the change in incidence of the disease, and highlighted papers that explored the possibilities of germline genetics.
He referenced two papers based on studies of colorectal cancer patients under the age of 40 and under the age of 35 that showed relatively low relationships to genetic predisposition based on incidence rates of germline mismatch repair mutations (Lynch Sydrome) bi-allelic MutYH mutations or Li-Fraumeni Syndrome.
“These data are actually quite consistent, whether or not from a single institution or whether or not it’s from a large national family registry over a longer period of time, what we’re actually recognizing is that much of what we actually see is not easily explained by mendelian cancer genetic syndromes,” Dr. Gruber said.
He also explored whether or not population genetics is a likely explanation for the rising incidence of early age onset colorectal cancer. Gruber pointed out that polygenic risk scores — which can identify numerous, individual loci across the human genome that contribute modest risk of colorectal cancer — can ultimate help measure genetic susceptibility. But he said doubts that any singular genetic factor has influenced the rise in adolescent and early adult incident rates.
Dr. Gruber put a lot of his emphasis on the need to address modifiable risk factors as possible correlations to the rise of early-age onset colorectal cancer risk. He highlighted a paper that presented factors that decreased risk (including aspirin, physical activity, statins, vegetable consumption) and those that increased risk (alcohol consumption, Body Mass Index, smoking, processed meat consumption).

He also specifically highlighted coffee consumption and the risk of colorectal cancer and highlighted a study conducted by Stephanie Schmit of the Cleveland Clinic that showed the more coffee people drank, the lower their risk of colorectal cancer. He also pointed out that decrease in coffee consumption and the slight rise of energy drinks over the past decade or so might have led to a microbiome change that might have led to increased risked, but he said it would be hard to postulate that any single risk would be hard to correlate that to the rise in early onset colorectal cancer incidence.

Dr. Gruber also acknowledged and expressed concern about the significant factor that systemic racism plays in the inability to address these disparities in incident and survival rates. He pointed out that the survival rates for those who have early onset colorectal cancer are lowest among individuals with lower socioeconomic status, while the highest survival rates are associated with the people with the highest socioeconomic status.

Ultimately, more questions than answers still remain in the fight against the rising tide of early-age onset colorectal cancer.

“I think it’s actually less likely to be polygenetic risk than it is poly risk, which will include things like medications, physical activity, diet and other trends and changes in risk factors that hopefully we will be able to explore with the same specificity that we are now understanding through genetic studies,” Dr. Gruber said. “It is going to take our collaboration and a lot of work to answer the question that we do not yet understand: Why is there an epidemic of early age onset of colorectal cancer? We have an obligation and an opportunity to understand why the risk of colorectal cancer is rising in early age onset individuals.”

Other highlights of Day 2 included Session II: “The Dimensions of the EAO-CRC Problem: Do We Have Accurate, Regular, Up to Date Measurement of Key Metrics Describing the Early Age Onset Colorectal Cancer Public Health Crisis.” That included an updated about the rising early-onset CRC trends and racial disparities, the impact of COVID-19 on CRC screening and an under-19 incidence and mortality report. Session III was a panel discussion that explored “Risk Assessment/Family History Ascertainment” and included discussions about CRC screening guidelines, increased access to genetic testing and patient access to appropriate care.

To watch Friday’s or Saturday’s presentations, register for the Early Age Onset Colorectal Cancer Summit and access the recorded programs.

The Early-Age Onset Colorectal Cancer Summit continues on Sunday, May 16 with Session IV: a moderated panel discussion titled, “How to Provide Timely, Effective, Quality of Life & Fertility Preserving Treatment: What Are Key Elements of Coordinated Care for Early Onset Colorectal Cancer?” at 10:30 a.m. ET. A panel of experts will offer input about patient perspective, nurse navigation, genetics, medical oncology and new therapeutics, surgery, financial burden/toxicity, radiation oncology, psychological needs, pediatrics and palliative care.

That will be followed at 1 p.m. ET by breakout sessions about “Understanding and Addressing Disparities in Early-Age Onset Colorectal Cancer” and “Integrating Music Therapy in Cancer” before the conference concludes with Session V at 2:25 p.m. ET, a program titled “How Did This Happen? Investigating the Causes of Early Onset Colorectal Cancers.”

We’re not delivering appropriate, evidence-based guideline-driven information about colorectal cancer to people early enough for them to take an appropriate action. We need to start our messaging earlier.” — Whitney Jones, MD, Colon Cancer Prevention Project

With that straight-forward message, Dr. Whitney Jones kicked off the seventh annual Early-Age Onset Colorectal Cancer Summit kicked off on Friday, May 14. The three-day conference, which is being held online because of ongoing Covid-19 precautions, is organized by the Colon Cancer Foundation, a New York-based 501(c)3 non-profit organization dedicated to reducing colorectal cancer incidence and death.

According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related deaths in men and in women in the U.S., and the second most common cause of cancer deaths when men and women are combined. It’s expected to cause about 52,980 deaths in the U.S. in 2021. The overarching etiology of the disease has not been established; there is no definitive cause of colorectal cancer.

Although the rate of people being diagnosed with colon cancer or rectal cancer each year has dropped overall since the mid-1980s, that’s mainly due to the increased prevalence of people getting screened and reducing lifestyle-related risk factors.

From 2013 to 2017, incidence rates dropped by about 1 percent each year. But that downward trend is mostly in older adults and masks rising incidence among younger adults since at least the mid-1990s. From 2012 through 2016, it increased every year by 2 percent in people younger than 50 and 1 percent in people 50 to 64.

The hypothesis, Jones says, is that under age-50 colon cancer is driving up the overall colorectal cancer incidence rate because healthcare providers and organizations are talking about it to patients too late, particularly in states with the highest colon cancer prevalence.

While it is believed the United States Preventive Task Force (USPSTF) is on the verge of announcing a new recommendation that will lower the age of screening to 45 to 49, Jones, the founder of the Colon Cancer Prevention Project, reinforced the need for primary care physicians, nurses, hospitals, pharmacies, GI surgeons, OB-GYNs and other healthcare providers and organizations to begin communicating to patients much earlier than age 50, which has been the status quo for decades.

In his introductory presentation, titled, “Improving the Earliest Possible Diagnosis and Treatment through Timely Recognition of the Symptoms and Signs of Young Adult Colorectal Cancer,” Jones said earlier messaging and lead time can help change people’s behaviors, especially for individuals with challenging socioeconomic variables or a known high-risk genetic history.

Identifying symptoms, understanding family history and preventative lifestyle modifications are often discussed too late with patients, he said. Even when an individual experiences initial symptoms, because process typically starts so late, there is often a long lag until definitive diagnosis and treatment can occur.

Early messaging needs to begin much earlier — perhaps extending all the way back to the early 20s or even teenage years, he said, especially because 60 percent of early age onset colon cancer cases are sporadic and not related to family history. That, he said, is the only way to go on offense against colon cancer and allow individuals to be proactive, rather than being on defense and forcing patients to be reactive.

“For us to really combat this and make progress in the next 10 years, we don’t need to study first and then act. We need to act on what we know right now. We need more awareness, more messaging. We need patients, hospitals and healthcare providers to get onboard and be aware, and we can simultaneously try to better understand the etiology, do dissemination and implementation research and better use logistics and technology. But we don’t need to wait on action until we have got the research puzzle figured out.”

In addition to Dr. Jones’s introduction, Friday’s kick-off session also included related topics from four other presenters:

– Introduction of the Echo Chamber Challenge and Clinical Alert: Erin Peterson, Director of Mission & Partnerships, Colon Cancer Coalition;

– How will EAO-CRC Incidence and Mortality Rank in 2040? Lola Rahib, PhD, Director of Scientific & Clinical Affairs, Cancer Commons’
– How to Involve Primary Care in Improving Earliest Stage Diagnosis: Len Lichtenfeld, MD, MACP, Former Deputy Chief Medical Officer, American Cancer Society; Board of Trustees, CancerCare;
– and a Colorectal Cancer Patient Story: Lisette Caesar, EdD, Founding Principal, Mosaic Preparatory Academy.

Friday’s events concluded with a virtual cocktail and networking event and a conversation with digital artist Andre’ Oshea, who was commissioned to create an inspirational tribute piece in memory of actor Chadwick Boseman that will be auctioned. Boseman died of colon cancer last year at the age of 43. Proceeds from the auction will benefit the Colon Cancer Foundation.

To watch Friday’s presentations, register for the Early Age Onset Colorectal Cancer Summit and access the recorded program.

On Day 2 on Saturday, May 15, opening remarks will be made by Susan Wysoki, Interim Executive Director, Paltown Development Foundation and Shannon Lee-Sin, a stage IIIc colon cancer survivor. Cindy R. Borassi, EAO-CRC Host and President, Colon Cancer Foundation, will present, “Framing the Conversation: Strategic Challenges in Current Medical Care that Contribute to Young Adult Colorectal Cancer (CRC) Incidence and Mortality,” followed by the keynote address by Stephen B. Gruber, MD, PhD, MPH, Vice President, City of Hope National Medical Center.

 

The titular study published on March 30, 2021 was a comparative effectiveness study, a study that compares two or more health interventions to evaluate which poses the greatest benefit and harm, and was inspired by and relied on the International Duration Evaluation of Adjuvant (IDEA) trial. The IDEA trial was a pooled analysis of six randomized clinical trials that studied patients with stage III colon cancer and compared the effects of three months of adjuvant chemotherapy to the standard duration of six months. 

Adjuvant chemotherapy refers to the additional therapy given to cancer patients after their primary therapy; in this case, the primary therapy was surgery. Adjuvant chemotherapy is administered to maximize the benefits of the primary therapy and to decrease the risk of cancer recurrence.

In the IDEA trial, the adjuvant therapy was either adjuvant 5-flourouracil/leucovorin plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX). Both FOLFOX and CAPOX are chemotherapy regimens used for advanced colorectal cancer, and, as stated, both contain oxaliplatin, a known neurotoxic agent. Therefore, the implications of reducing the duration of adjuvant therapy are immense, as it could potentially decrease the neuropathic effects of the drug, as well as reduce treatment cost and increase treatment adherence.

The IDEA trial in particular was chosen as a benchmark due to the many controversies that surrounded the study’s findings. The IDEA trial found that “a shortened duration of adjuvant chemotherapy was noninferior among patients with T1 to T3 and N1 stage disease and among patients prescribed CAPOX.” In this case, noninferior means that the experimental treatment, i.e. the shortened adjuvant chemotherapy, is not substantially worse than the control treatment, i.e. the standard six month duration of adjuvant chemotherapy. 

This was controversial, as a worldwide survey of 145 oncologists showed that 1 in 3 supported the six months duration of adjuvant chemotherapy. Additionally, there were concerns as to how these findings could be generalizable to a real-world population of cancer patients.

This current study aimed to remedy these controversies by conducting a target trial emulation, a method used by investigators to mimic a clinical trial using observational techniques. Though randomized clinical trials continue to provide the strongest evidence for comparing the effectiveness of two or more interventions, they can be slow, costly, and at times impossible to conduct due to ethical considerations. Therefore, target trial emulations, in which an ideal clinical trial is imitated using already-existing, real-world data, can prove useful.

This study utilized the data of patients who were diagnosed with stage III colon cancer between January 2004 and December 2015 in Alberta, Canada, and the eligibility criteria mimicked that of the IDEA trial. Overall, 485 patients were included in the trial emulation, with 230 being women and the median age being 59 years.

Both a target trial emulation and a naive observational analysis were conducted, a naive observational analysis being one that did not take into account any of the factors of the target trial emulation. More specifically, the naive observational analysis did not factor in allowable reasons for therapy cessation, values that change over time like treatment dosage, or immortal time bias. 

In this study, the findings of the target trial emulation and the naive observational analysis differed. The findings of the target trial emulation mirrored that of the original IDEA trial; a shortened duration of adjuvant therapy, specifically CAPOX, was found to be noninferior to the standard six month duration. However, the naive observational analysis found that a shortened duration of CAPOX therapy was associated with a decreased overall survival for patients. 

According to the authors, these disparate findings show “the importance of explicitly emulating a target trial when conducting comparative efficacy research using real-world data.”

 

Earlier this month, the U.S. Food and Drug Administration (FDA) authorized Medtronic and Cosmo Pharmaceuticals to start marketing its novel artificial intelligence (AI) device, the GI Genius, that improves the quality of colonoscopies by detecting precancerous polyps that clinicians may otherwise overlook if they are flat or are located in areas of the colon that are difficult to see with an endoscope.

 

According to a systematic review and meta-analysis of 43 international publications, 13 of which were conducted in the United States, many cases of colorectal cancer can be attributed to polyps and adenomas that are not detected during routine screenings. The study found that 26%  (95% CI: 23%-30%) of adenomas are missed during colonoscopies as well as 27% of serrated polyps (95% CI: 16%-40%). GI Genius is one of a few devices cleared by the FDA to aid in colonoscopies and is the first computer-aided detection (CADe) system that uses AI to recognize polyps. The tool was reviewed through the FDA’s De Novo premarket review pathway for low-to-moderate risk novel devices.

 

The GI Genius works by emitting a sound and displaying green markers that are superimposed over the endoscope video when it recognizes a potential lesion; it is compatible with many video endoscopy systems. GI Genius utilizes an algorithm to recognize polyps that was developed by reviewing over 13 million colonoscopy videos. Gastroenterologists labeled tissues as being either healthy or unhealthy to help “teach” the GI Genius how to distinguish the two. While the GI Genius can recognize unhealthy tissue, it does not characterize lesions and is not a substitute for lab sampling to diagnose the tissue in question.

 

The safety and effectiveness of the GI Genius were assessed through a large randomized controlled trial in Italy. Out of a subpopulation of 263 subjects who required screening or surveillance at least every three years, 136 patients had a colonoscopy with the assistance of the GI Genius, while 127 patients served as controls and underwent a standard colonoscopy. In the experimental group, adenomas or carcinomas were detected in 55.1% of patients, while they were only identified in 42% of patients in the control group. No adverse events related to the use of GI Genius were reported, although its use led to a small increase in the amount of healthy tissue that was biopsied.

 

Overall, GI Genius shows great promise as a way to enhance the quality and reliability of colonoscopies by aiding physicians who may otherwise miss polyps that are hard to see.

Updated phase III results from the BEACON study have found that encorafenib with cetuximab can lead to promising survival outcomes among patients with advanced colorectal cancer (CRC) who had received previous lines of treatment.

The third most common cancer and the third most common cause of cancer-related deaths in the U.S., CRC occurs when there is development of mutations in oncogenes, tumor suppressor genes, and genes that aid in DNA repair. Depending on the site of the mutation, CRC can be classified as familial, inherited, or sporadic. Chromosomal instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP) are pathogenic mechanisms through which CRC can develop. These mutations, changes in the chromosomes, and translocations can affect various signaling pathways (Wnt, TP53, TGF-β, and MAPK/PI3K) and genes such as c-MYC, KRAS, BRAF, SMAD2, and SMAD4. Oftentimes, mutations in these genes can serve as important predictive markers in the context of patient outcomes.

In addition to CRC, mutations in BRAF have been found to be responsible for various other cancers such as melanoma, thyroid, small-cell lung, and hairy cell leukemia. BRAF encodes for  the B-RAF serine/threonine kinase protein, which is a part of the RAS/RAF/MEK/ERK pathway. Most of the mutations that take place in the BRAF gene lead to a V600E substitution, which often leads to a poor prognosis in patients. The BRAFV600E mutation initiates activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which causes the tumor cells to rapidly divide. It has been estimated that approximately 10% of patients with metastatic CRC have a mutation in BRAF.

In the past, treating metastatic CRC with BRAFV600E mutations has led to low response rates, partly due to incomplete inhibition of the MAPK signaling. Recently, the combination of a BRAF (encorafenib) and EGFR (cetuximab) inhibitor has shown promising results compared to BRAF inhibitor monotherapy. The BEACON CRC study is a randomized, open-label, phase III trial that enrolled 665 patients and compared triple combination therapy; encorafenib (300 mg x1 a day) plus binimetinib (45 mg 2x a day) plus cetuximab (400 mg/m2 x1 a week) versus double combination therapy; encorafenib plus cetuximab versus cetuximab plus irinotecan or FOLFIRI. Of the total 665 patients, 224 received triple therapy, 220 received double therapy, and 221 received the control therapy.

The objective of the BEACON trial was to detect the overall survival in relation to the triple combination therapy/double combination therapy as compared to the control. It was determined that triple/double therapy led to a median overall survival of 9.3 months, while the control group showed an overall survival of 5.9 months. This indicates that both triple/double therapy improved the overall survival rate and can therefore be used as the new standard of care in patients with metastatic CRC with BRFV600E mutations.

 

 

In February 2021, Brett Walker, M.D., became the 10th awardee of the Thomas K. Weber Colorectal Cancer Research Scholar Award, awarded by the Colon Cancer Foundation in partnership with the Society of Surgical Oncology.

The award was renamed in 2020 after Thomas K. Weber, M.D. (1954-2019), founder and former president of the Colon Cancer Foundation. Dr. Weber devoted his life to increasing colorectal cancer awareness, detection, and prevention, and his dedication to “a world without colon cancer” lies at the heart of the Colon Cancer Foundation. Thus, the award was renamed to keep his legacy alive while celebrating members of the community that display excellence in translational research pertaining to the molecular biology of colorectal cancer.

This year, Dr. Walker received the award for his abstract submission on circulating hybrid cells (CHCs) as a potential biomarker for treatment response in gastrointestinal cancers. CHCs are a type of hybrid cell created by the fusion of an immune cell and a tumor cell. Research pertaining to CHCs is novel as the primary focus of previous studies on cancer cell biomarkers has been on circulating tumor cells (CTCs), cells that bud off from a primary tumor and circulate in the bloodstream. 

Though CHCs also disseminate outward from a primary tumor and circulate in the peripheral blood, the difference between the two lies in their names. Whereas CTCs only express cytokeratin, a tumor protein, CHCs express both cytokeratin and CD45, an immune cell marker. It is postulated that CHCs have both immune and tumor cell markers in order to successfully evade the immune system to form new tumors. 

“CHCs have this opportunity to escape out of the primary tumor and migrate to different areas and potentially seed new metastatic tumors,” said Dr. Walker in an email correspondence with the Colon Cancer Foundation. 

According to Dr. Walker, CHCs have the potential to be a better evaluative marker of treatment response and disease progression compared to CTCs because there are more of them circulating in the bloodstream. 

Dr. Walker’s research itself indicates the effectiveness of CHCs as biomarkers. According to The ASCO’s Post description of his research, CHCs “successfully discriminated pathologic complete response from non–pathologic complete response in both rectal and esophageal cancers.”

Additionally, Dr. Walker mentioned that CHCs can provide information on the actual tumor itself. 

“By collecting CHCs, we can actually gain information on the tumor, specifically what proteins they express and their genetic makeup including mutations, which could potentially help guide targetable treatments for patients,” said Dr. Walker.  

Though more studies need to be conducted into CHCs, the implications of the research conducted by Dr. Walker’s laboratory are immense. If indeed CHC levels can be used as an effective biomarker, then patients with colorectal cancer can opt for non-invasive blood tests to track disease and treatment progression, as opposed to undergoing traditionally invasive imaging techniques and endoscopies. This in turn improves patients’ quality of life by avoiding intensive procedures that can cause stress and fear. 

 

Dr. Walker expressed excitement over CHCs as a biomarker and hopes that his research will inspire others in the field to conduct their own studies. 

 

“I think that there’s a huge opportunity here for us to really affect how we both detect and manage colon cancer. And so I really think this is an awesome opportunity to bring attention to hybrid cells and hopefully expand the number of researchers in this field.”

 

Cancer has a massive impact globally, with an estimated 1.8 million cases per year in the U.S. The advances in screening, early diagnosis, and treatment modalities have greatly improved cancer-related morbidity and mortality. With approximately 16.9 million cancer survivors as of January 2019 in the U.S. alone, this number is only expected to grow. When diagnosed, many of these survivors were probably working, thus needing to adapt their lifestyle and work ability around their diagnosis and upcoming treatment. However, this aspect of cancer survival receives very little coverage in research and modern-day media.

The National Comprehensive Cancer Network’s (NCCN) 2021 Virtual Annual Conference highlighted many important aspects of cancer survivorship. Speaker, Anna J. Tevaarwerk, M.D., from the University of Wisconsin Carbone Cancer Centre, highlighted the importance of accommodating cancer survivors returning to work. Her talk, titled, ‘Helping Cancer Survivors Return to Work,’ discussed the impact of cancer and its treatment on a survivor’s work ethic, performance, and/or employment satisfaction and how employers can better assimilate survivors who choose to or need to work during or after their treatment.

 

The ‘Return to Work’ Issue

During her presentation, Dr. Tevaarwerk shared that around 46% of those diagnosed with cancer are in the 20-64 age group—the ‘working age group’ in the U.S. So, most are either in the workforce, in school, or not in the workforce. Additionally, the average retirement age in the U.S. is 64, but this is predicted to rise. This highlights how cancer survivors may have to undergo and recover from treatment while remaining within the working age group.

This also means, that the majority of patients or survivors will either want or need to continue working after their diagnosis. But evidence indicates that their successful return to work post-diagnosis is much more challenging than it should be. Some of these work limitations are physical and are likely to impair their ability to work:

  • Increased fatigue
  • Decreased stamina
  • Lack of productivity and the persistent side effects of the treatment itself Additionally, the numerous appointments and frequent sick leave associated with cancer treatments can interfere with daily tasks, resulting in unpredictable absences from work. Psychosocial, mental, and/or emotional issues may also emerge when a person is diagnosed with cancer, leading to:
    • Decreased confidence in being able to work
    • Reduced self-esteem
    • Increase anxiety about being shunned at work
    • Fear of being a burden on your colleagues or employer

While most survivors appear ‘normal’ on the outside, many of these psychological and psychosocial stressors associated with cancer treatment and self-confidence/body dysmorphia anxiety (e.g., hair loss associated with chemotherapy), can often make it very hard for survivors to return to work. Unfortunately, many are unable to stop working or reducing their work hours even during active treatment – especially with patients receiving palliative (treatment targeting the symptoms rather than the cancer itself) or non-curative (treatments that slow progression and tumour growth) treatments that are ongoing and need to remain in the workforce.

 

Consequences of Work Limitations

Explaining the impact of the above stressors on patients who need to work, Dr. Tevaarwerk said, “Cancer treatment creates demands on patient time that may impact employment and may require job accommodation such as increased personal calls or messages during work hours, perioding breaks for rest, reduced physical exertion, job restructuring and/or modification, provision or mobility assistance, improved building access and parking close to your work area, or modified office temperatures.

As a survivor with, undergoing, or recovering from cancer and its treatment it can be quite challenging to ask for these adjustments from your employer and can leave survivors feeling productively inadequate. Additionally, the impact of reducing work hours may lead to financial toxicity that culminates in treatment delays/lack of treatment adherence, treatment discontinuation, health insurance threat (becoming uninsured/paying for increased out-of-pocket expenses), lack of stable income, and psychosocial distress.

For many survivors, work also means a lot more than income—survivors may continue or want to return to work because, as Dr. Tevaarwerk says it creates a sense of normalcy, distraction, need for activity, and social contacts.” While there is no direct line between these concepts, it is important to highlight that work is important for a lot of reasons outside of income, and many survivors may find a sense of purpose that encourages them to continue to return to work.

 

Post-Diagnosis Work Outcomes

Cancer employment support varies widely in the U.S. depending on the system you are operating in, according to Dr. Tevaarwerk. Work-related productivity due to loss of health may change significantly, with lower levels of productivity happening after diagnosis and at the end of treatment, she said, with the main driver being absenteeism, which includes a loss of working days due to treatment. Additionally, patients receiving curative treatment have shown increased work ability, decreased work limitations, and a steady rise in hours worked when compared to their counterparts receiving palliative cancer therapy.

Dr. Tevaarwerk added that due to the stigma surrounding cancer, and the possibility of being laid off or misrepresented at work, patients find it extremely difficult to share their diagnosis and treatment plans with their employer. Thus, a majority of the time the type of treatment a cancer patient is receiving is unclear, meaning that employment facilities tend to be inadequately prepared to support a cancer patient either during (if they decide that they are in the position where they are able to comfortably continue working) or after their treatment. She added that the phrase ‘return to work’ is misleading as it “implies that a cancer survivor stops working and then re-starts only once at the exact same job,” when in reality a cancer survivor may never stop working, or may stop and start more than once, or may take up a very different level or job.

 

Overcoming Work Limitations and Barriers

To make returning to work successful, it is important for employers and their employees who are survivors to work together to create an accommodative environment that supports both their needs. A proactive discussion between both parties can help establish physical and emotion boundaries. Dr. Tevaarwerk highlighted several key things an employer can do to support the successful return of a cancer survivor to work:

  • A proactive discussion between the employer and employee to establish work-related boundaries (performance adjustments, work intensity etc.)
  • Increasing the availability of emotional support options within the workplace (physical work-place adjustments, increased work-from home hours, staggering schedules etc.)
  • Making shared decisions to mitigate work impact

Conclusion

Overall, the return to work of a survivor is complicated and influenced by numerous factors and the work ability and performance of a survivor or patient often depends on survivor characteristics, work conditions (flexibility/climate), and the interplay between complex employee-employer social systems. Being at work is considered both necessary and fulfilling, and is strongly associated with mental, emotional, physical, and therapeutic benefits for those suffering from chronic conditions like cancer. Therefore, understanding the ‘return-to-work’ dilemma that cancer survivors face and adjusting it to be more accommodative would open up a range of opportunities that could benefit both the employer and the survivor.

 

The American Cancer Society’s 2021 Cancer Facts and Figures includes staggering statistics about colorectal cancer (CRC) in the United States:

  • It is the third most common type of cancer diagnosed in men and women
  • It is the third leading cause of cancer-related deaths in men and women
  • CRC incidence rates are increasing in adults younger than 50
  • CRC mortality rates are increasing in adults younger than 55
  • Black people have the highest CRC incidence and mortality rates among all ethnic groups

These shocking figures are why Fight CRC, a patient advocacy group with a mission to “cure colorectal cancer,” is working with members of Congress to provide funding for CRC research.

Fight CRC calls for the allocation of $20 million for a CRC research program within the Department of Defense (DoD). Congressional champions of the group are leading a letter to the House Appropriations Committee in support of this effort. According to the letter, CRC is the only cancer among the top five cancer killers without its own program within the DoD’s Congressionally Directed Medical Research Program (CDMRP). 

Fight CRC wants to change that. They believe it is past time for CRC to be spotlighted, and they have “no plans of slowing down or stopping until they reach their goal: a cure.” At the Colon Cancer Foundation, we wholeheartedly stand by this mission and we will continue to work towards, in the words of founder Dr. Thomas K. Weber, “a world without colon cancer.”  

Imagine a world in which CRC is not one of the most common types of cancers. Imagine a world in which CRC does not cause deaths anymore. Now, imagine that you don’t have to imagine any of this: you can make this world a reality by clicking on Fight CRC’s action alert and urging your members of Congress to sign the letter to create a distinct program for CRC research. Share it with your friends, family, and colleagues so that together, we can all create a world without CRC.