Colorectal Cancer Treatment
Treatment at UT MD Anderson’s Gastrointestinal Center combines the latest technology and research with a multidisciplinary team approach tailored to your unique needs.
Our team of surgeons use minimally invasive techniques, including advanced robotic surgery, that reduce recovery time and maximize quality of life. UT MD Anderson also offers clinical trials for patients at every disease stage, from newly diagnosed small tumors to patients with stage IV cancer.
Colorectal cancer treatment plans
Colon cancer that has not spread to distant parts of the body is usually treated with surgery. Some patients then receive chemotherapy or, less commonly, radiation therapy to kill any remaining cancer cells.
Rectal cancer that has not spread is usually treated with surgery. These patients may receive chemotherapy or radiation therapy before the procedure. They may also undergo these treatments after surgery to kill any remaining cancer cells.
If colorectal cancer has spread, or metastasized, to distant parts of the body, some patients can still be cured. With new treatments, colorectal cancer that has spread can often be managed like a chronic condition and care is meant to prolong life and preserve quality of life. Treatments for all patients with metastatic colorectal cancer can include surgery, radiation therapy, cryotherapy, microwave ablation, and cancer drugs like chemotherapy, targeted therapy and immunotherapy.
Surgery
Surgery is the most common treatment for colorectal cancer, especially if it has not spread. Surgery for colorectal cancer is most successful when done by a surgeon with a great deal of experience in the procedure. At UT MD Anderson, these procedures are performed by surgeons who specialize in colorectal cancer surgery and are national and international leaders in the field. Surgeons around the country often refer their patients to UT MD Anderson surgeons for their expertise, especially for the most difficult cases.
The type of surgery depends on the stage and location of the tumor. Visit the colon cancer treatment page or rectal cancer treatment page to learn about the surgical procedures for each disease.
Chemotherapy
Chemotherapy drugs kill cancer cells, control their growth or relieve disease-related symptoms. Chemotherapy may involve a single drug or a combination of two or more drugs, depending on the type of cancer and how fast it is growing.
Targeted Therapy
Targeted therapy drugs are designed to stop or slow the growth or spread of cancer. This happens on a cellular level. Cancer cells need specific molecules (often in the form of proteins) to survive, multiply and spread. These molecules are usually made by the genes that cause cancer, as well as the cells themselves. Targeted therapies are designed to interfere with, or target, these molecules or the cancer-causing genes that create them.
Radiation therapy
Radiation therapy uses powerful, focused beams of energy to kill cancer cells. There are several different radiation therapy techniques. Doctors can use these to accurately target a tumor while minimizing damage to healthy tissue.
Radiation therapy is frequently used to treat rectal cancer. For colon cancer, it is used only in very limited situations.
Cryoablation
Cryoablation, also known as cryotherapy or cryosurgery, uses cold to kill tumor cells. During the procedure, a special probe is inserted into the tumor and then cooled to temperatures well below freezing. A ball of ice forms at the tip of the probe, freezing and destroying cancerous tissue. Cryotherapy is not as invasive as surgery and can sometimes be performed as an outpatient procedure.
Microwave ablation
Microwave ablation uses heat to kill cancer cells. During the procedure, a probe delivers microwaves directly to the tumor, heating the tissue until it is destroyed. Microwave ablation is not as invasive as surgery and can sometimes be performed as an outpatient procedure.
Immunotherapy
The immune system finds and defends the body from infection and disease. Cancer is a complex disease that can evade and outsmart the immune system. Immunotherapy improves the immune system’s ability to eliminate cancer.
There are two types of immunotherapy currently used to treat colon cancer:
- Immune checkpoint inhibitors stop the immune system from turning off before cancer is completely eliminated.
- Monoclonal antibodies attach to specific proteins on the surface of cancer cells or immune cells. They either mark the cancer as a target for the immune system or boost the ability of immune cells to fight the cancer.
Angiogenesis inhibitors
Angiogenesis is the process of creating new blood vessels. Some cancerous tumors are very efficient at this process. New blood vessels increase blood supply to a tumor, allowing it to grow rapidly. Angiogenesis inhibitors, or anti-angiogenic therapy, disrupt the creation of these blood vessels.
Clinical trials
Clinical trials are a key component of UT MD Anderson's mission to end cancer. Patients may volunteer to participate in these research studies, which help doctors improve cancer prevention, diagnosis and treatment.
Some clinical trials allow patients to receive experimental medications or treatments, though not all patients are eligible.
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Immunotherapy and colorectal cancer: Where we are and what’s ahead
The immune system defends the body from viruses and bacteria. But it’s not as successful in killing cancer on its own. Immune checkpoint inhibitors – a type of immunotherapy – harness the immune system to treat many types of cancers, including colorectal cancer.
They work by blocking signals in a tumor that stop the immune system from working. By preventing these signals, checkpoint inhibitors allow immune cells – called T cells – to target cancer.
Here, I’ll share more about how immunotherapy is used to treat colorectal cancer and the research we’re doing at UT MD Anderson.
Which immune checkpoint inhibitors treat colorectal cancer?
There are four immune checkpoint inhibitors that have been most effective in treating colorectal cancer.
- pembrolizumab
- nivolumab
- ipilimumab
- dostarlimab
They’re approved by the Food and Drug Administration (FDA) for patients with a subtype of metastatic colorectal cancer called microsatellite instability-high (MSI-H) disease.
What is microsatellite instability-high colorectal cancer?
Patients with microsatellite instability-high colorectal cancer have a lot of genetic mutations inside a tumor that fuel its growth. Patients may also hear the term “deficient mismatch repair” (dMMR) or “mismatch repair (MMR) deficient” to describe this subtype.
These genetic mutations are sometimes linked to a hereditary syndrome called Lynch syndrome, but sometimes they occur sporadically. This means they aren’t passed down through a family member.
Microsatellite instability status is determined through a molecular profile, which is a series of tests performed on tissue that’s removed during biopsy to learn a tumor’s genetic makeup. Molecular profiling is considered universal testing, so all colorectal cancer patients should undergo it. It can help guide immunotherapy treatment.
A clearer distinction between cancer and normal cells
To the immune system, foreign pathogens look very different from normal cells. But the difference with cancer cells isn’t as clear – except in microsatellite instability-H disease.
Patients with MSI-H colorectal cancer are more likely to have their immune systems detect that tumors are different from normal tissue. This helps lay the groundwork for immunotherapy to be effective.
The good news is the immune cells often recognize the cancer cells as different. The barrier is the checkpoints – or the signals – that the tumor cells put on their surface to prevent the immune cells from attacking.
This is where immune checkpoint inhibitors come in. They block the signal from the tumor cells that prevents the T cells from doing their work.
Only 3% of patients with metastatic colorectal cancer have MSI-H disease.
But this is a subset of patients where we can say, “Despite having metastatic disease, we can cure you with immunotherapy.” That hasn’t been possible with chemotherapy and targeted therapies.
Discovering other colorectal cancer subtypes
UT MD Anderson researchers recently discovered a less common subtype of metastatic colorectal cancer that responds well to immunotherapy.
They led a study that found that tumors with a specific subtype of mutations in the POLE gene, called loss-of-proofreading (LOP) mutations, are very responsive to immune checkpoint inhibitors. These findings are important because not all POLE mutations behave in the same way. We now know that patients we identify with the LOP subtype may benefit from immune checkpoint therapy.
Overcoming barriers to treat metastatic colorectal cancer
We believe the remaining 97% of patients with metastatic colorectal cancer that isn’t MSI-H can be divided into two groups. My colleagues and I have developed a tool called the Consensus Molecular Subtype (CMS) classification system to help subtype colorectal cancer.
CMS4 tumors
One group is patients with CMS4 tumors. Their T cells are activated and want to attack cancer, but they can’t enter the tumor’s microenvironment. It’s like the tumor sets up a chain link fence that keeps them out. When examined under a microscope, the T cells cluster along the edges of a tumor, trying to get in.
This is the case with colorectal cancer tumors that have spread to the liver. Instead of the T cells being spread throughout the tumor, they are mostly located near the edge, making them less effective. In analyzing these types of tumors, we’ve discovered that the tumor microenvironment in the liver looks different than other parts of the body. Namely, it’s full of immune cells that cause immunosuppression and do not help control cancer.
Our research is aimed at breaking down the chain link fence to allow the T cells to enter the tumor microenvironment. Once inside, we hope the T cells can be effective in killing the tumor with the help of immunotherapy.
It’s not about activating the immune system; that's done thanks to immunotherapy. It's about targeting the tumor microenvironment to get the T cells inside first.
CMS2 and CMS3 tumors
In patients with CMS2 or CMS3 colorectal cancer, the T cells show little to no activity in response to the tumor. We refer to it as the ‘immune desert.’ When viewed under the microscope, the immune system shows little evidence of reacting.
The strategy is less about the tumor microenvironment – which may still be a problem – and more about getting the immune system to even recognize that there's something going on.
One approach is personalized vaccines. They work by instructing the patient’s cells to produce proteins based on the mutations driving the cancer’s growth. The immune system then searches for other cells with the mutated proteins to clear them out.
Another opportunity is with cellular therapies like CAR T cell therapy, T cell therapy and CAR NK cell therapy, which are being explored through clinical trials. With T cell therapies, we take the few, rare T cells that are in the tumor, expand their numbers in a lab and give them back to the patient. Or, we manufacture T cells that we design in a lab to be better equipped to attack the cancer.
Research to find and treat metastatic colorectal cancer earlier
A big part of the research we’re doing now is developing new strategies to treat micrometastatic colorectal cancer. This is cancer that has spread from the primary tumor in tiny amounts – too small to be seen on traditional scans or blood tests. It is sometimes referred to as minimal residual disease (MRD). Patients with MRD are more likely to have a cancer relapse.
We’re researching how we can detect MRD through circulating tumor DNA (ctDNA) testing. We know as tumors get bigger and the number of cancer cells increases, they start building up defenses against the immune system. This is when immunotherapy becomes less effective.
Based on earlier research, we know that really small micrometastatic deposits can be sensitive to immunotherapy. So, we want to identify the cancer earlier – even before scans pick them up – and find immunotherapies to best treat these patients. There are a few different immunotherapy combinations being explored in clinical trials right now.
We’re excited about the progress that’s been made in immunotherapy to treat colorectal cancer, and we hope to develop new ways to benefit even more patients.
Scott Kopetz, M.D., Ph.D., is a gastrointestinal medical oncologist and associate vice president for translational research at UT MD Anderson.
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