Advanced Colorectal Cancer
Colorectal cancer begins in the colon or rectum, which is the end of the large intestine. When cancer spreads to other regions of the body, most commonly to the liver, lungs, or bones, doctors refer to it as “advanced” or metastatic (stage IV disease).
According to data from 2023, 67% of new colorectal cancer cases in Abu Dhabi were discovered at a late stage, which has a negative impact on health outcomes and reduces survival rates. Furthermore, persons may develop advanced disease when a tumor that was treated years ago comes back. Cancer-killing chemotherapy drugs may leave behind certain cells that do not react to the treatment. Even high-powered scans fail to identify them at first, allowing them to remain concealed until the cancer cells develop into a tumor large enough to be discovered by imaging.
Some people may not experience symptoms, but many do. Symptoms vary depending on the size of the tumor and its dissemination. Liver metastasis can turn the skin yellow or itching (jaundice) and cause gastrointestinal discomfort and nausea. Tumors in the lungs can make breathing difficult.Treatments can nearly always alleviate the majority of these symptoms.
Treatment Options for Colorectal Cancer
Surgically removing the cancer is the most common treatment for many stages of colorectal cancer. Chemotherapy, radiation, targeted therapy, immunotherapy, radiofrequency ablation, and cryosurgery are other treatments that may be used to treat colorectal cancer, depending on its stage.
Because of an increased risk of recurrence, differences in anatomy, and poorer prognosis, the treatment of rectal cancer may differ from that of colon cancer. Although surgery remains a common type of treatment for local and locally advanced rectal cancer, people with some stages may be treated with radiation, chemotherapy, and/or targeted therapy with or without surgery.
Depending on stage and type of tumor, among other factors, the ASCO Guideline summarizes shared knowledge from many researchers and clinical studies and recommend personalized treatment plans for patients with metastatic colorectal cancer. In addition to these standard treatments, researchers continue to study both new treatments, such as immunotherapies, and new combinations of existing treatments in clinical trials.
What Are Treatment Options for Advanced Colorectal Cancer
For advanced colorectal cancer, the best treatments are ones that travel through the bloodstream to all parts of the body, such as chemotherapy. Some chemotherapy medications function better together, so patients could require to take two or more at the same time. However, because these medications target all fast dividing cells, they may destroy both cancer cells and healthy cells. This implies they can cause side effects such as hair loss and mouth sores. These issues normally resolve after treatment.
“Targeted” treatments are drugs that attack specific characteristics only cancer cells have to stop them from growing. As targeted medicines preferentially adress cancer cells they usually cause fewer side effects than chemotherapy drugs and therefore can also be used as a constant treatment.
Immunotherapy is another treatment that is often given. It helps the body´s immune system to find disseminated cancer cells, and to destroy them.
The most suitable course of therapy is determined by individual cancer cell characteristics, the extent to which the cancer has spread, the patient’s overall health, any symptoms or treatment side effects that may occur, and the patient’s own expectations and preferences. Everyone has the freedom to make their own decisions. You may choose to battle cancer as aggressively as possible, using as many therapies as you can take. Alternatively, you may feel more comfortable doing less in an advanced situation and focusing on quality time with your loved ones.
Clinical Trials for Advanced Colorectal Cancer
Treatment selections might be tough, especially if the cancer is advanced. In this case, patients or loved ones may look for edge-cutting choices. TheKnowHow second opinion service can assist you distinguishing between proven or promising choices and untrustworthy services.
In addition, a clinical trial could be a viable and reliable choice when confronted with an advanced cancer disease. Let us explain, what you should know about clinical trials.
What Are Clinical Trials?
Clinical trials are medical research studies which investigate into prospective innovative drugs, new ways to deliver therapies, or other forms of treatments and compare them to existing ones. Initially, researchers examine potential novel medicines in the laboratory. If they demonstrate safety and efficacy in cell culture and/or animals, researchers will continue to careful human testing. In the first phase of the clinical trial, healthy volunteers will take the new drug to ensure their safety. A phase 2 study enrolls a small number of patients for an initial efficacy comparison. If the examination yields favorable findings, more patients will be recruited for a phase 3 clinical trial. This is frequently carried out concurrently in many nations and regions, giving patients a higher opportunity of participating.
There are numerous possible benefits to participating in a study, but there are also some potential drawbacks to consider. Positive effects of participating in a clinical trial can be
- getting a new treatment before it’s widely available
- being one of the first to benefit if the drug or treatment works
- receiving additional monitoring and care by regular tests and check-ups
- helping advance medical knowledge for the benefit of other patients now and in the future
Often, studies are randomized, so you won’t know whether you’re getting the novel or usual treatment. However, some research has shown participating in a study enhances long-term survival even if you do not receive the novel treatment. It has been argued that hospitals conducting medical research deliver superior care.
What are the disadvantages of taking part in a clinical trial? Clinical trials frequently entail an experimental treatment. Therefore, you should be aware of the following disadvantages that may result from participating.
- Consenting to participate in a trial does not guarantee you will receive the new medicine. As studies compare novel treatments to existing treatments, you may be chosen by lot to receive the standard treatment.
- The new treatment may not work better than the standard treatment.
- The new treatment might have unanticipated adverse effects.
- The clinical trial may cause inconvenience as additional medical appointments may take your time. You may also need to travel to the study site multiple times or stay in the hospital.
What Is a Clinical Trial?
Let us give you an example.
The ERASur trial compares total ablative therapy plus usual systemic therapy to usual systemic therapy alone in treating patients with colorectal cancer that has spread to up to 4 body sites (limited metastatic).
The usual approach for patients who are not participating in a study is treatment with intravenous (IV) (through a vein) and/or oral (pills that are swallowed) medications (“systemic therapy” = a medication given to the whole body) to help stop the cancer sites from getting larger and the spread of the cancer to additional body sites.
“Ablative therapy” means that the intention of the local treatment is to eliminate the cancer at that metastatic site. The ablative local therapy will consist of very focused, intensive radiotherapy called Stereotactic Ablative Radiotherapy (SABR) with or without surgical resection and/or microwave ablation, which is a procedure where a needle is temporarily inserted in the tumor and heat is used to destroy the cancer cells. SABR, surgical resection, and microwave ablation have been tested for safety, but it is not scientifically proven that the addition of these treatments are beneficial for the advanced stage of cancer.
The addition of ablative local therapy to all known metastatic sites to the usual approach of systemic therapy could shrink or remove the tumor(s) or prevent the tumor(s) from returning.
Other clinical trials may involve the use of a novel medicine, using an approved medicine in applying it another way, for example in a combination with other medicine or with radiation, or approaches like vaccines targeting characteristis of aggressive cancer cells.
Immunotherapy for Patients With Hereditary Colorectal Cancer
Approximately 5 – 10% of colon cancer cases are caused by hereditary syndromes that hamper our body cells’ natural capacity to repair damage to our genes, which are coded by a chemical material called DNA. When our body cells are renewed, they divide and replicate their DNA to create new cells. During DNA replication, mistakes may occur, and our cells have a variety of repair agents available to correct them. Our genes also provide a blueprint for producing these repair molecules. Sometimes the build plan itself contains mistakes, which might be inherited as a family trait. Affected family members suffer from distinct tumor syndromes that develop at a young age as a result of occurring faults in proliferating cells not being fixed.
Lynch syndrome is such an inherited DNA repair disorder. People with this disorder have an increased risk of developing colorectal cancer, typically before they reach the age of 50. Lynch syndrome colorectal cancer tumors have many mutations.
People whose colorectal tumors have a genetic feature known as “microsatellite instability-high (MSI-H)” have another defect in repairing DNA replication errors, also called “mismatch repair”. MSI-H colorectal cancer patients also have many mutations in their tumors.
The bad news about such familial colorectal cancer types is that they develop at younger age, do not develop over many years from screening detectable polyps and therefore are diagnosed more often in late stage. About 15 percent of patients with stages II and III colorectal cancer and about 5 percent of those with stage IV disease have MSI-H tumors. The good news is that because these DNA repair defective tumors have many mutations in their genome, the immune system may better recognize them as “strangers”. As a result, immune therapy is an effective option for these types of cancer.
The immune checkpoint inhibitors nivolumab (Opdivo), ipilimumab (Yervoy), and pembrolizumab (Keytruda) have all been approved for the treatment of metastatic colorectal cancer in patients with Lynch syndrome and in patients with MSI-H cancers.
In addition, immune therapy drugs a also tested in clinical trials. As an example, the COMMIT study is testing the addition of atezolizumab (Tecentriq) to the combination of chemotherapy and the targeted therapy bevacizumab (Avastin), for treating patients that have defective DNA mismatch repair. The hope is that combining drugs that work in different ways will improve treatment results in patients with colorectal cancer.
Using targeted therapies for metastatic colorectal cancer
Using targeted therapies against genetic mutations that may drive tumor growth is another key area of research for metastatic colorectal cancer. The goal is to find agents that can block the activity of the abnormal proteins produced by specific mutations. In around 10 – 15% of colorectal cancer patients the tumors have aquired a specific mutation in a gene called BRAF. Around one in three of these patients also show the microsatellite instability-high (MSI-H) variation. So far, patients with BRAF mutations showed a poor prognosis. New drugs targeting the abnormal BRAF protein, however, show promising results:
- The drug encorafenib (Braftovi), which targets the BRAF protein, is approved for the treatment of some patients with colorectal cancer. This drug is used in combination with cetuximab (Erbitux) and the chemotherapy combination FOLFOX in adults with metastatic colorectal cancer whose tumors have a certain mutation in the BRAF gene and who have already undergone treatment.
- In a small clinical trial, the targeted drug dostarlimab (Jemperli) completely shrank tumors in people with locally advanced rectal cancer whose tumors had a mismatch repair (microsatellite instability-high (MSI-H) deficiency. Most of the patients who have been followed for at least 2 years have not had a recurrence.
- Another trial showed that colorectal cancer that contains mutations in the BRAF gene responds to treatment with the drug vemurafenib (Zelboraf) in combination with cetuximab and irinotecan (Camptosar).
A combination of two targeted drugs, tucatinib (Tukysa) and trastuzumab (Herceptin) is approved for people with advanced colorectal cancer that produces an excess amount of a protein called HER2. This tumor characteristic is seen in less than 3% of people with advanced colorectal cancer.
Liver transplantation an Option for Metastazised Colorectal Cancer?
Expectations of long-term survival in metastatic colorectal cancer are mainly restricted to patients amenable for radical resection of the primary tumor and the secondary lesions. This is restricted to patients with metastatic spread limited to the liver. For all other patients, long-term survivorship is realistically attainable only by immunotherapy in tumours with deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H).
Therefore, when the disease is liver limited, but not initially resectable, the joint effort of multidisciplinary teams including oncologists, surgeons, radiotherapists, and interventional radiologists is necessary to achieve complete eradication of liver metastasis. Intensified cytotoxic treatment combined with targeted or immune therapy and increasingly complex interventional procedures can achieve conversion to resectability in around half of the patients.
By contrast, if metastatic disease is not amenable for complete eradication, the outcome is almost invariably fatal. When surgery is not feasible because of insufficient remnant of healthy tissue or involvement of critical structures, liver transplantation may be a solution.
The 2024 TransMet study published in The Lancet was the first randomized controlled multicenter study to show an improvement in survival rates for patients who receive a liver transplant in addition to chemotherapy (5 year survival rate of 73%) when compared with patients who only receive chemotherapy (5 year survival rate of 9%). The researchers concluded that these findings should prompt clinical oncologists to reconsider liver transplantation as a valuable option for unresectable liver-limited mCRC patients meeting TransMet criteria, and transplantation agencies to adapt their policies of access to organ donation.
Confronted With Advanced Colorectal Cancer?
Many people with advanced colorectal cancer have common concerns. Here are some tips that may help:
Stay ahead of pain: Not everyone will suffer from the condition or its treatments. But if you do, you don’t have to just accept it. If you’re experiencing symptoms, talk to your doctor. You may require a new medicine or treatment that shrinks your tumor. It may also assist to have a pain specialist on your cancer care team.
Stay active: When you get enough rest and exercise, your mood improves and you also feel less tired. It may even help you live longer.
Stay connected: Cancer and your treatment can make you feel lonely sometimes. You may feel as if no one really understands what you are going through. It is helpful to reach out to others, whether they be friends, a counselor, or a support group for persons with colorectal cancer. They may be there when you need someone to listen.
Stay positive: Treatment options for advanced colorectal cancer are constantly improving. Doctors are working hard to discover a cure.
Get an independent second opinion: When you are feeling confused or unsure about your treatment, a second opinion may be helpful. It may either confirm your current treatment plan and makes you feel confident, or add a new approach you and your doctors has not thought about so far.
TheKnowHow Independent Second Opinion
empowers patients with the knowledge they need to make informed decisions. Our unbiased oncology specialists provide a fresh perspective on treatment choices, fully explaining the benefits and drawbacks of each available option. TheKnowHow report does not just add another opinion, add another choice, and makes decisions even harder. We help you understand your condition and your options, and we guide you through the decision-making process.
Your Health Matters !
A contribution by Dr. Gabriele Stumm,
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