Colorectal Cancer: Leveraging Awareness and Early Detection

Jedrzej Wykretowicz, MD

Colorectal cancer (CRC) misconceptions often exist regarding screening and diagnosis specifically. Some believe symptoms are always present, screening is only for symptomatic individuals, and colonoscopy is the only option, but none of this is true.

To address these misconceptions and existing disparities, education is key, and initiatives like CRC awareness month are in place to further understanding.

Advancements in screening have been developed over recent years, including stool-based tests like the fecal immunochemical test (FIT) and FIT-DNA, as well as the blood-based methylated septin 9 (mSEPT9) test which is FDA-approved. Research and policy changes like those in the Affordable Care Act have also worked to address inequalities in access to screening and treatment and remain key moving forward.

Another advancement used for screening patients with CRC is circulating tumor (ct)DNA testing. The blood test is also used to monitor recurrence of disease, as well as to guide treatment decisions. The future of ctDNA is promising and more advancements are expected in ctDNA isolation, enrichment, and detection.

In an interview with Targeted Oncology^TM, Jedrzej Wykretowicz, MD, PhD, oncologist, Virginia Oncology Associates, discussed the importance of early detection and taking steps towards the prevention of CRC.

Targeted Oncology: In your experience, what are some of the biggest misconceptions that people have about colorectal cancer?

There are numerous misconceptions, but they mostly cluster around screening and diagnosis. Some of them are that colorectal cancer always presents with symptoms of abdominal pain, bleeding, weight loss, which is not the case. That leads also to the misconception that screening is only required for somebody with symptoms, which is a diagnostic workup, not screening anymore.

As far as screening goes, I think a lot of people think that colonoscopy is the only screening option. We have various different screenings for patients who do not want to undergo colonoscopy. But also, that stems from a misconception that colonoscopy is something that is very difficult to do because of a prep, potential pain, and other problems. While some of it might be true, in general, it's a procedure that goes well and there is a lot of experience doing it.

Some additional misconceptions are around who gets colorectal cancer, that this has to be older people, that you need that family history of colon cancer. While some of it is obviously correct, a lot of patients do not have a family history. I do see a lot of patients in the clinic that are much younger than what you would normally think.

Colorectal cancer image: © mi_viri - stock.adobe.comNormal

What can be done to further address these disparities?

It's an easy answer in a way that it is education, and screening is important. Colon cancer awareness month is actually 1 of these interventions. It has national attention that can bring this to people's attention, and on an individual level, physicians, families, celebrities getting involved, that definitely helps. It is all about repetition that screening is needed.

Early detection is crucial for successful treatment. What are some of the latest advancements in screening methods for colorectal cancer?

Colonoscopy is the gold standard, and that is what's considered to be the best test. However, for patients who cannot have a colonoscopy or decided against having a colonoscopy, there has been development in stool-based techniques like FIT which uses antibodies against hemoglobin, which is a bit better than the previous test that required special preparation, vs a FIT-DNA test that uses some additional molecular markers, potentially increasing how sensitive it is. The FDA approved a blood-based test; however, it is only approved for patients who are offered screening and who declined because of a sensitivity [that] is not that good. However, it is better than not getting screened at all. It is a methylated septin 9 test that is available as a blood test.

While disparities in access to screening and treatment exist, what are some of the initiatives working to address these inequalities?

That can be answered with 3 different kinds of tiers. One is research. We have a lot of research showing disparities, and I don't think that is a surprise. It is research that addresses what leads to these disparities, because that will help us solve them, address them, and create interventions to improve outcomes.

On a policy level, the Affordable Care Act is a great example where not only patients get insurance that increases access, but also some other provisions. For example,

cost sharing for preventive services has been eliminated. Lower deductible plans and cancer screening itself has been considered an essential health benefit. Some of these changes on a policy level obviously help too.

[Lastly,] national attention, so colon cancer awareness month, NCCRT, so National Colon Cancer Roundtable, and cooperation from other groups is important. The CDC has the Healthy People 2030 initiative that also addresses some of generating data and disparities, and some social determinants of health, which hopefully will help us show how much progress we [can] make and where we can make better changes.

Can you discuss ctDNA testing and how it is used for diagnosing and monitoring colorectal cancer?

ctDNA is a blood-based test that looks for molecular changes in the blood that are characteristic for cancer. Cancer cells release active genetic material into the blood. It is a small amount compared with all genetic material that is floating around from normal cells. When it is detected, it can be used for screening purposes. That test that is already approved can be used for monitoring after treatment, or monitoring for recurrence. These are some of the uses that are being developed right now vs interest in using ctDNA in patients who are already treated to detect resistance mechanisms to create chemotherapy. There is a pretty broad spectrum where it can be used, starting with screening and diagnosis through treatment, and then further along.

How does ctDNA testing compare with traditional methods like biopsies? What are some of its advantages and limitations?

Biopsy is still the gold standard. I do not think ctDNA is the replacement for a standard biopsy at this time. However, it is convenient, it is a blood draw, it is more acceptable to patients, and because of that, it is also easier to obtain several, or as many as you want, readouts at a certain interval, for example, every 3 months or every 6 months, so that makes its use unique.

The downsides are the sensitivity. We are talking about a small amount of molecular material or genetic material. That is pretty unstable, so it can miss cancer, it can miss diagnosis because of that. Some of the improvements that are being developed are in regards to the sensitivity. Cost is always an issue. Of course, this is costly, because it is decreasing, which is great, but definitely the more tests you do, the more cost you add, so that is definitely a downside of this technique.

Are there any specific scenarios where ctDNA testing is particularly useful?

Right now, the most typical scenario is in someone who had colon cancer surgery with a curative intent. ctDNA is used in 2 main ways: 1 is to decide whether it is someone who should have or normally would be recommended to chemotherapy. Could they omit chemotherapy potentially? It is a de-escalation of treatment, meaning you do not over-treat patients who require treatment. The opposite is also true in patients who may not normally require chemotherapy, based on clinical characteristics. So less advanced cancer. If we would find circulating tumor DNA, we might consider being more aggressive. That is actually escalation of therapy, and potentially increasing cure rates. These are 2 common scenarios.

Another is monitoring after treatment. If somebody's finished the therapy, and you want to detect recurrence earlier, [we] might want to check ctDNA, because these changes in the blood of molecular material can be detected earlier than a lot of typical clinical

findings like imaging or symptoms, which happens later.

What are some of the most exciting advancements in ctDNA technology and research related to colorectal cancer?

The advancements happen sort of in the background for somebody like me who is a clinician and sees patients in the clinic. This is development on the assay side. We have very small amounts of circulating tumor DNA, so improving isolation of the DNA from the blood, improving enrichment of this material, and then of course, the assay itself, so making the sensitivity ability to detect changes, making it better, and then of course, on the cost side, using less equipment and less costly equipment is going to improve the way we can use it.

[On] the clinical side, that is where my interest is a bit more, how I can use it to help patients. I would like to see research where we can show that using ctDNA in that particular scenario does change decision-making and that I can comfortably recommend against chemotherapy based on the assay. That is coming along, and we are still trying to get all this data.

In your opinion, how will ctDNA impact the future of colorectal cancer diagnosis and treatment?

It is a technique that is being developed and has shown tremendous progress. It is coming into use and I think we are going to be using it [for] the whole patient journey from screening, early detection, through therapies and a curative setting, but also for patients who are being treated for more advanced stages to find the right therapies, to find the right clinical trials, to determine resistance, and adjust therapies as we move move along the treatment pathway. I think it is going to be an integral part of what we are doing in the future.

What resources would you recommend for a community oncologist seeking more information about treating and managing patients with colorectal cancer?

Guidelines are obviously something that everybody is familiar with. [The American Society of Clinical Oncology, the National Comprehensive Cancer Network, or the European Society of Medical Oncology] guidelines [are things one] should be familiar with. I personally use X, formerly Twitter. There are quite a few accounts from academic oncologists, from community oncologists, from various organizations where [one] can find good information, often the same day that they are released. There are discussions and various opinions, so I use it as 1 of my main news sites.

If somebody likes more audio vs multiple online resources with audio, webinars, interviews, research to practice comes to mind, and journals too like Targeted Oncology, for example. I think people should find something that they like to do in their spare time, because it is usually the time you spend outside of the clinic when you catch up on that news.

Colon Cancer Awareness Month starts in March, [and] I am hopeful that this is helpful for communities to increase their awareness of and importance of screening.