Colorectal cancer stage IV and what it means

Colorectal cancer often begins with a polyp, an abnormal growth of tissue inside the colon or the rectum. Initially, polyps grow and project from the innermost layer of the colon and rectum wall (mucosa) into the inside cavity. Cancerous polyps also grow deeper and spread into the outer layers of the colon or rectum wall and sometimes beyond the wall into the lymph nodes and other parts of the body. Not all polyps are cancerous, but there is no way to tell which polyp will develop into cancer.  Therefore it is best practice to remove all polyps.

There are several tests to screen for colorectal cancer. Colonoscopy is a method that allows the doctor not only to look for polyps inside the colon and rectum but also to remove these polyps, a procedure called polypectomy. Once removed,  polyps are examined whether they are cancerous (a procedure called a biopsy).

If your polyp was confirmed to be cancerous and you were diagnosed with colorectal cancer, your doctor will order additional tests to determine the depth your cancer has penetrated the colon or rectum wall, tumor grade, how far it spread to other organs, number of positive regional lymph nodes or in other words what stage is your disease. Staging helps your medical team to determine what treatments are most appropriate for you.

Staging tests may include imaging procedures such as CT scans for the chest, abdomen, and pelvic areas, complete blood count (CBC), chemistry profile, and  measurement of CEA. In many cases, the stage of your cancer may not be determined until after colon cancer surgery.

Tumor Grade is an indicator of tumor aggressiveness and how rapid the cancer is likely to grow.  Cancer cells are observed under the microscope and are assessed based on their appearance. For colorectal cancer, tumors are graded on a scale of 1 to 4.  Cancer cells that resemble normal cells are considered low grade (Grade 1), and are projected to grow and divide slowly. Cancer cells with abnormal structure, suggest they can divide rapidly are considered as high grade (grade 4).

The stages of colon and rectal cancer are:

For each colorectal cancer patient, a specific treatment plan will be developed based on the type of cancer, how far it spread (stage), how fast it grows (tumor grade) and taking into account patients’ overall health, as well as the patient’s goals.  The plan is developed by a medical team that usually consist of:

• A Gastroenterologist, a doctor who is specialized in treating disorders of the digestive system (gastrointestinal tract).
• A Surgical Oncologist or Colorectal surgeon
• A Medical Oncologist, a doctor who is specialized in treating cancer with drugs such as chemotherapy, targeted therapy or immunotherapy.
• A Radiation oncologist, a doctor who is specialized in radiation therapy.
• Additional members of the team may include nurses, a social worker, a psychologist, and a nutritionist.  

Treatments could be divided into local treatments that affect only the site of the cancer or systemic treatments that affect the whole body.

Because colorectal cancer treatments often damage healthy cells and tissues, side effects are common. Before treatment starts, your health care team will explain possible side effects and suggest ways to help you manage them. More information about side effects.

At this stage, cancer has spread through the lymphatic system and /or the bloodstream and metastasized in distant organs such as liver, lungs, peritoneum, ovaries in women and even to the brain. The extent of cancer spread is determined by colonoscopy, blood work, chemical profile, and CT scans of the chest, abdomen and pelvis.

Guidelines also recommend that tumors from patients with stage IV colorectal cancer will be tested for several biomarkers including KRAS/NRAS gene status. In patients with  normal KRAS/NRAS gene status of BRAF should be tested. The gene status of these genes, will help determine the benefit of adding a specific targeted therapies to the chemotherapy regimen.

Majority of patients diagnosed with metastatic colorectal cancer have unresectable disease, because the cancer has spread to too many organs, and surgery of the colon or rectum alone will not eliminate the cancer in other sites. Therefore, chemotherapy is the main treatment, for stage IV colorectal cancer patients.

In some cases, surgery might still be needed, especially if cancer is blocking the colon or rectum or is likely to do so.

If there are only a few small areas of cancer metastases in the liver or lungs, those specific sites could  be potentially removed by surgery to relieve symptoms of the disease and prolong patients’ life. Alternatively, liver or lung metastases could be destroyed by radiofrequency ablation therapy (RFA) and chemotherapy will be given as well.

If metastases are too big or there are too many, treatment with chemotherapy for 3-6 months may reduce their size and number and increase the possibility for surgery. Chemotherapy before surgery is called neoadjuvant chemotherapy. Those patients will also receive chemotherapy after their surgery, also called an adjuvant therapy.

It is important to understand that surgery in stage IV colorectal cancer is mostly for relieving symptoms of the disease. For certain patients, removal of metastases  will not only improve the quality of life but also provide surgical cure and improve survival.

Most people with stage IV cancer will be treated with chemotherapy and/or targeted therapies to control the cancer.

Types of Targeted therapies:

Targeting EGFR signaling in cancer cells, blocks the ability of cells to divide rapidly.

• Cetuximab - an antibody against EGFR
• Panitumumab - an antibody against EGFR

Targeting VEGF blocks the ability of cells to attract new blood vessels into the cancer

• bevacizumab [Avastin] - a humanized antibody against VEGF,
• ziv-aflibercept [Zaltrap] a biological drug that inhibits VEGF
• ramucirumab [Cyramza]) An antibody that inhibits VEGF

Regorafenib (Stivarga) alone

• A small molecule that inhibits multiple signaling proteins

Some of the most commonly used regimens include:

• FOLFOX: leucovorin, 5-FU, and oxaliplatin (Eloxatin)
• FOLFIRI: leucovorin, 5-FU, and irinotecan (Camptosar)
• CAPEOX or CAPOX : capecitabine (Xeloda) and oxaliplatin
• FOLFOXIRI: leucovorin, 5-FU, oxaliplatin, and irinotecan
• 5-FU and leucovorin, with or without a targeted drug
• Capecitabine, with or without a targeted drug
• Irinotecan, with or without a targeted drug
• Cetuximab (an antibody against EGFR) alone
• Panitumumab (an antibody against EGFR) alone
• Regorafenib (Stivarga) alone
• Trifluridine and tipiracil (Lonsurf)
• One of the above combinations plus either a drug that targets VEGF, (bevacizumab [Avastin], ziv-aflibercept [Zaltrap], or ramucirumab [Cyramza]), or a drug that targets EGFR (cetuximab [Erbitux] or panitumumab [Vectibix])

The choice of regimens depends on several factors, including any previous treatments you’ve had and your overall health.

If one of these regimens is no longer working, another may be tried. For people with certain gene changes in their cancer cells, another option after initial chemotherapy might be treatment with an immunotherapy drug such as pembrolizumab (Keytruda).

For advanced cancers, radiation therapy can also be used to help prevent or relieve symptoms such as pain. It may reduce the size of the tumors for a time, but it's not likely to cure the cancer. If your doctor recommends radiation therapy, it’s important that you understand the goal of treatment.

Surveillance for metastatic disease: Patients with stage IV colorectal cancer who had their primary cancer and metastatic removed, and are with no  evidence of disease (NED) should remain under surveillance. Your health care team will continue to check to ensure the cancer has not returned, manage side effects, and monitor your overall health. Patients should be monitored by CT scans of the chest, abdomen and pelvis  every 3-6 months in the first 2 years. Blood test for CEA, should be done every 3-6 months in the first 2 years  and every 6 years and every 6 months for the total of 5 years.

Immuno-oncology: Is a type of systemic cancer treatment that helps your immune system fight cancer. Currently immuno-oncology is FDA approved for patients with metastatic colorectal cancer whose tumors have a feature called microsatellite instability (MSI-H) and have progressed on other standard chemotherapy for colorectal cancer. Only a small percentage of metastatic colorectal cancer are MSI-H. More information about immuno-oncology.

Clinical Trials: Patients can enter clinical trials before, during, or after starting their cancer treatment. Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not improved. Some clinical trials test new ways to stop cancer from recurring or reduce the side effects of cancer treatment. Find out if a clinical trial is right for you, through the Alliance’s Clinical Trial Finder.