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Diagnosis overview

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:

  • Stage 0

    Stage 0. The earliest stage also called cancer (or carcinoma) in situ. Cancer cells are found only on the innermost layer (the mucosa) of the colon or rectum wall.

  • Stage I

    Stage I. The cancer has grown beyond the mucosa and invaded the adjacent layers  (submucosa and maybe the muscle layer) but is contained within the colon or rectum wall.  Cancer has not spread to nearby lymph nodes (small organs that are part of the immune system)

  • Stage II

    Stage II cancer has spread through the colon or rectum wall but has not spread to the regional lymph nodes. Stage II could be further divided into three stages:

    • Stage IIA cancer has spread through the outermost layer of the colon or rectum wall (serosa) but has not spread to other organs or the regional lymph nodes.

    • Stage IIB cancer has spread through the colon or rectum wall to the tissue that is wrapped around the internal organs, the lining of the abdomen, also called visceral peritoneum. Cancer has not spread out to the nearby lymph nodes.

    • Stage IIC cancer has spread through the colon or rectum wall to nearby abdominal organs. Cancer has not spread into nearby lymph nodes or other organs in the body.

  • Stage III

    Stage III Cancer has spread from the innermost layer, the mucosa, through the adjacent layers of the wall (submucosa and the muscle layer) and into nearby lymph nodes (small organs that are part of the immune system). Stage III colorectal cancer could be further divided into three stages:

    • Stage IIIA cancer has spread from the mucosa, the innermost layer of the wall to the adjacent layers, the submucosa and maybe into the muscle layer and to 1-3 lymph nodes. Cancer has not spread to other organs.

    • Stage IIIB cancer has grown and spread beyond the outermost layer of the colon or rectum wall (serosa).  Cancer has also spread into 1-3 lymph nodes, However, cancer has not spread to other nearby organs.

    • Stage IIIC cancer can be of any size and remain within the wall or expand beyond the wall of the colon or rectum to the abdominal lining, the visceral peritoneum.  Cancer has also spread into 4 or more nearby lymph nodes. However, cancer has not spread to other nearby organs.

  • Stage IV

    Stage IV Cancer has spread beyond the wall of the colon or rectum, into the nearby lymph nodes and into other, remote organs such as liver, lung, and peritoneum. Stage IV colorectal cancer can be divided into three stages:

    • Stage IVA cancer has spread beyond the colon or rectum wall to one other remote organ such as liver or lungs, or ovary and also to the nearby lymph nodes.

    • Stage IVB cancer has spread beyond the colon or rectum wall to more than one organ such as liver, lungs, and ovaries as well as to nearby and distant lymph nodes.

    • Stage IVC cancer has spread beyond the colon or rectum wall to distant part of the abdominal lining (the visceral peritoneum) and may have spread to other distant organs and lymph nodes.

Treatment overview

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.

Localized treatments

  • Surgery

    Surgery, is the most common treatment for early stages colorectal cancer and most useful when cancer is localized in the early stages of the disease.  Colectomy is a surgical procedure that consist of the removal of the tumor, the surrounding healthy tissue and the nearby lymph nodes. In some cases, surgery is also used in patients diagnosed with later stages of the disease. Once, the cancer is removed, the remaining healthy ends of the colon or rectum will be re-attached to each other. Normal bowel function is often restored in about a week.

    Colectomy can be done by an open surgery for which, the surgeon will make a long, vertical cut of the belly to access the colon or rectum.  Colectomy can also be done by a laparoscopic surgery , a minimally invasive technique, in which the surgeon cut few small incisions of the belly and a video camera is inserted through one of the cuts to assist the surgeon perform the surgery with specific tools through the other incisions.  

    In the case that the healthy ends of the colon or the rectom cannot be attached together (temporarily or permanently), then, one end will be directed out of the body through a stoma, an opening in the abdominal wall and skin.  A ring placed on the abdominal wall will hold the end of the colon or rectum in place. A member of your care team will instruct you on how to manage the stoma following your surgery.

  • Radiation therapy

    Radiation therapy is also considered a local therapy. This therapy uses high energy x-rays to kill the cancer cells.  The x-rays are directed to the specific location of the tumor. Radiation therapy is a common treatment for rectal cancer and could be given before or after surgery. Radiation therapy is not frequently used for colon cancer, except when there is a concern that a tumor is growing back in its original location. Radiation therapy is usually given five days a week for several weeks.

Systemic treatments

  • Chemotherapy

    Chemotherapy is the most commonly used systemic therapy. Chemotherapeutic drugs kill cancer cells by blocking their ability to grow and divide, they also affect some healthy cells which is the reason patients experience side effects. Over the years, multiple chemotherapeutic drugs were developed for treating colorectal cancer.  Chemotherapy is usually given multiple times (cycles) over a period of time. Your medical oncologist and the care team will decide whether you receive one drug or a combination of different drugs. In some cases, chemotherapy could be given before surgery to reduce the size of the tumor, or after surgery to kill any remaining cancer cells that were not removed.

  • Targeted therapy

    Targeted therapy is a type of systemic therapy also given as pills or directly into the bloodstream. Targeted therapies are drugs (chemicals) that were developed to block the specific driving forces within the cancer cells that allow them to grow and divide.

    Because these forces are mainly active in cancer cells and not in healthy cells, these treatments are less toxic to healthy tissues and organs. Not all colorectal cancer share the same targets.  Your medical oncologist will order a biomarker test that will characterize the specific driving forces of your tumor and help determine the most suitable targeted therapy for you. In most cases, targeted therapy is used in combination with other treatments such as chemotherapy, radiation therapy and/or surgery.

Side effects

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.

Treatment for stage IV

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.

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