In this expert Q&A, Dr. Scott Kopetz explains when surgery may still play a role in metastatic colorectal cancer (mCRC), how disease develops, and why biomarker testing at diagnosis is so important for guiding treatment decisions.
1) Is surgery a possible treatment route for patients with mCRC?
Dr. Scott Kopetz: Stage IV disease is metastatic, meaning that at diagnosis, the tumor has spread beyond the areas that would traditionally be removed with surgery.
That said, stage IV patients can still sometimes have surgery. In fact, about 20% of patients have disease that has spread in a more isolated pattern, where surgery can be incorporated into the treatment plan for metastatic disease. CRC is actually somewhat unique in that regard.
For many other cancer types, once the disease has spread to distant organs, surgery is no longer beneficial. With CRC, a subset of patients have disease that, for reasons we don’t fully understand, spreads in a very contained or confined way.
Unfortunately, for about 80% of patients, the cancer spreads in a more disseminated pattern, meaning there may be small amounts of disease in multiple organs or different areas of the body.
2) Do patients typically present with metastatic disease at diagnosis, or is it more often a recurrence after earlier-stage disease?
Dr. Scott Kopetz: It’s actually about evenly split. Many patients are diagnosed with metastatic disease from the start. Others may have initially had early-stage disease that was surgically removed, and they may even have received adjuvant therapy to reduce the risk of recurrence. But despite that, the cancer can still come back later as metastatic disease seen on imaging.
3) When should patients with mCRC have biomarker testing?
Dr. Scott Kopetz: Biomarkers help define the different subtypes of CRC. We use the term “colorectal cancer” broadly for anything that arises in that organ, but we know there are different tumor biologies and behaviors within that category.
One important subtype is MSI-high disease. This testing can be done through next-generation sequencing or through tumor tissue staining to look for MSI-high status, also called deficient mismatch repair (dMMR).
What this tells us is how the tumor formed and what went wrong biologically. In this case, there’s a problem with repairing DNA. When the cell divides, the DNA damage doesn’t get repaired properly, so mutations build up much faster than in other tumors.
As a result, these tumors look very different from normal cells in the body. Most cancers actually look very similar to healthy cells, which is why the immune system often struggles to recognize them. But MSI-high tumors look dramatically different from normal colon cells.
Because of that, the immune system is often already aware that these cells may not belong there. These tumors tend to respond very well to immune checkpoint inhibitors, so we think of MSI-high disease as a very distinct subtype. In many cases, the immune system is already engaged — we just need to give it a small push to create a strong and durable response.
There are classic biomarkers that are recommended for every patient whose disease has spread beyond the primary tumor or lymph nodes, essentially, anyone with metastatic disease. We recommend biomarker testing as soon as a patient is diagnosed because it can significantly impact first-line treatment decisions.
So the message is: test everyone, and test at diagnosis.
Biomarker testing recommendations are also continuing to evolve, and updates to the guidelines are currently in progress.
Want to learn more from Dr. Kopetz? Tune into the full webinar discussion for a deeper discussion on biomarker testing, treatment options, and advances in care.
