Monitoring Residual Disease in Colon Cancer

As part of our coverage of the European Society for Medical Oncology (ESMO) 2018 Congress, held October 19–23 in Munich, we are speaking with Luis Diaz, MD, about monitoring for residual disease in colon cancer. Dr. Diaz heads the division of solid tumor oncology at Memorial Sloan Kettering Cancer Center in New York City, and is also a medical oncologist specializing in the care and treatment of patients with colon and pancreatic cancers. On October 20, he will be giving a talk entitled, “Monitoring Molecular Residual Disease in Colon Cancer: Implications for the Future.”

-Interviewed by Anna Azvolinsky

Cancer Network: Could you define what molecular residual disease is in colon cancer?

Dr. Diaz: This is a very important concept in which there is going to be a lot of new knowledge. The concept of minimal residual disease is important after definitive therapy-therapy that might cure you, but when you are done with that therapy, you don’t know if you are going to be cured, and so clinicians look for residual disease or minimal residual disease, which is disease that is so miniscule that it cannot be seen by the naked eye or on any scans or any other technology. Minimal residual disease can also be considered occult metastatic disease. There are developments in technology to detect minimal residual disease in such a way that we can make prognostic and therapeutic decisions.

Cancer Network: How big of an issue is molecular residual disease in colon cancer? Which patients does this apply to? How many patients that are treated and subsequently have no detectable disease should then be monitored molecularly?

Dr. Diaz: Basically, there are two groups of patients with cancer. There are the ones who possibly could be cured by surgery or early intervention, and the ones who have metastatic disease that will never be cured. For those patients who have metastatic disease, the concept of minimal residual disease doesn’t make sense, because you can virtually always see the disease with standard scanning and other detection methods. The patients with potential minimal residual disease are the ones with resected tumors. Roughly, about two-thirds of all cancer patients are at risk for minimal residual disease, and the other one-third are the metastatic patients who are not at risk. So, if we apply this to colon cancer, there are about 150,000 cases of colon cancer; here the numbers are a bit different. One-quarter of patients have metastatic disease in which minimal residual disease doesn’t really apply, and the other three-quarters are potentially cured with surgery, but in many cases, have presence of minimal residual disease.

Cancer Network: What are the available approaches or those in development to monitor molecular residual disease in colon cancer? Do these approaches differ compared with monitoring in patients with other solid tumors?

Dr. Diaz: I think that right now, the major techniques-CT and PET scans; protein biomarkers like PSA, CEA, or CA-125; and circulating tumor cells-have their advantages and disadvantages. The good thing about imaging is that these techniques are sensitive, but not specific, and they can also be used for localized scans. The problem is that imaging cannot always identify residual tumors because remaining tumor cells might be too small to detect. Protein biomarkers suffer from a lack of specificity and often are not sensitive enough either. Circulating tumor cells also suffer from a lack of sensitivity. However, other approaches like circulating tumor DNA and other protein biomarkers may give us the opportunity to detect minimal residual disease very early after a surgery.

Cancer Network: So, for something like circulating tumor DNA and perhaps other assays you mentioned, are these still in development in the research setting or are some already available for clinicians to use?

Dr. Diaz: Right now, we just have the studies that talk about these techniques as prognostic markers. The other thing we are trying to do is we need to decide whether we need to treat patients based on their minimal residual disease status. So, if you are positive and will recur, should you be treated? And, if you are negative for minimal residual disease, should you not receive further treatment? The major problem is that, currently, if you are positive for something like circulating tumor DNA, the likelihood you will recur is very high. However, if you are negative, that’s not an assurance that you won’t recur. Therefore, you can design studies for the minimal residual disease–positive patients, but not for the minimal residual disease–negative patients. We need better technology for that. We also need to be very careful that we do not get ahead of ourselves and say, “this is a really good intervention,” without having fundamental studies to show us that there is clinical benefit.

Cancer Network: Thank you so much for joining us today, Dr. Diaz.

Dr. Diaz: Thank you!

Financial Disclosure: Dr. Diaz is a member of the Board of Directors for Jounce Therapeutics and Personal Genome Diagnostics. He also holds equity in PapGene, Personal Genome Diagnostics, and Phoremost. He is a paid consultant for Merck, Personal Genome Diagnostics, and Phoremost. He is an inventor of licensed intellectual property related to technology for ctDNA analyses and mismatch repair deficiency for diagnosis and therapy from Johns Hopkins University. These licenses and relationships are associated with equity or royalty payments to Dr. Diaz. The terms of all of these arrangements are being managed by Johns Hopkins and Memorial Sloan Kettering in accordance with their conflict of interest policies. In addition, in the past 5 years, Dr. Diaz has participated as a paid consultant for one-time engagements with Caris, Cell Design Labs, Genocea Biosciences, Illumina, and Lyndra.