Overview of Colon Cancer

Understand the Signs & Symptoms Colon Cancer: Who's at risk? and the best tests for early detection

Signs-Symptoms-Diagnosis-Management & Treatment Advances for Colon Cancer

Medically reviewed by Dr. C.H. Weaver M.D. 8/2018

The colon and rectum are parts of the body’s digestive system and together form a long, muscular tube called the large intestine. The colon is the first 6 feet of the large intestine and the rectum is the last 8-10 inches. According to estimates from the American Cancer Society, more than 95,000 individuals will be diagnosed with colorectal cancer in the United States this year making colorectal cancer the third most common cancer among U.S. men and women. There is, however, good news about colorectal cancer in the U.S: death rates associated with the disease have been dropping for several decades, and advances continue to be made in screening, prevention, and treatment.[1]

  • Symptoms of Colon Cancer
  • Risk Factors for Colon Cancer
  • Diagnosis and Tests for Colon Cancer
  • Precision Cancer Medicine Testing for Colon Cancer
  • Screening and Prevention of Colon Cancer

Adenocarcinoma refers to cancer that begins in the cells that line the colon and accounts for over 90% of cancers originating in the colon. Other cancers, including carcinoid tumors and leiomyosarcoma, also originate in the colon, but are not referred to as colon cancer. This overview deals only with adenocarcinoma of the colon, which will be referred to as colon cancer.

Colon cancer begins in cells that line the colon. As the cells increase in number, they spread circumferentially around the colon like a “napkin ring.” If detected early, cancer cells may only be found in the colon. If not detected early, the cancer may invade adjacent organs and spread through the lymph and blood systems throughout the body to the liver, lungs and other organs.

The treatment of colon cancer typically consists of surgery and/or systemic therapy with chemotherapy or precision cancer medicines. Care may involve a gastroenterologist, surgeon, and a medical oncologist and be carefully coordinated between the various treating physicians to achieve the best outcome.

Symptoms of Colon Cancer

Symptoms and signs of colon cancer most commonly include blood in the stool or a change in bowel habits.

  • Visible blood in the stool or a darkening of stool color as a result of the presence of blood.
  • A change in bowel habits.
    • Diarrhea, constipation or a feeling that the bowel does not completely empty.
  • Pencil thin or narrowing of stool.
  • Bloating or frequent gas pains, fullness, or cramps.
  • Unexplained weight loss.
  • Fatigue
  • Vomiting

Risk factors for Colon Cancer

Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get colon cancer and not having risk factors doesn’t mean that you will not get cancer, it simply means that you are at greater risk than normal to develop the cancer.

Risk factors for colorectal cancer include the following:

  • Having a family history of colon cancer in a first degree relative (parent, sibling, or child).
  • Having a personal history of inflammatory bowel disease (Ulcerative colitis, or Crohn’s disease)
  • Having a personal history of previous colon, rectal, or ovarian cancer.
  • Having inherited changes in certain genes associated with familial colon cancer and polyposis syndromes.
    • Lynch syndrome
    • Familial Adenomatous Polyposis (FAP)
  • Smoking
  • Obesity
  • More than 3 drinks of alcohol per day.

Older age is also a risk factor for most cancers. The chance of getting cancer increases as you get older.

Diagnosis and Tests for Colon Cancer

Colon cancer is typically diagnosed during a colonoscopy which is performed because an individual has concerning signs or symptoms of colon cancer or as part of routine screening in individuals 45-50 or older. During a colonoscopy abnormal areas of the colon and polyps are biopsied. The tissue obtained during the biopsy is examined by a pathologist to confirm a diagnosis of colon cancer. Genomic profiling or biomarker testing is performed to see if the cancer can be targeted with precision cancer medicines. When colon cancer is confirmed additional tests are required to stage or determine the extent of spread of the cancer.

Upon completion of the clinical staging evaluation, surgery is performed to remove the cancer along with part of the normal adjacent colon and determine the level of spread within the colon and abdomen. Surgery is performed through an abdominal incision or through a laparoscope. Laparoscopic surgery is less invasive and involves the insertion of surgical instruments through very small incisions in the abdomen. Patients experience faster healing times compared with traditional abdominal surgery, and their outcomes with regard to cancer recurrence and survival have been shown in some trials to be similar.[1[ It is important for patients to discuss the risks and benefits of the two techniques with their doctor,. Laparoscopic surgery is not yet the standard of care and is best performed by a doctor experienced with the technique.

Following surgical removal of colon cancer and examination of removed tissue under a microscope, a final “pathologic” stage will be given.

Staging of Colon Cancer

In addition to colonoscopy determining the stage of the colon cancer or the extent of the spread requires a number of tests and is ultimately confirmed by surgical removal of the cancer and exploration of the abdominal cavity. The following tests may be used to look for cancer in the chest, abdomen and pelvis. A colon cancer’s stage is a key factor in determining the best treatment.

  • Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body. This method is more sensitive and precise than an X-ray.
  • Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and diseased tissue. MRI gives better pictures of tumors located near bone than CT, does not use radiation as CT does, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the tumor.
  • Colonoscopy: Because 3-5% of patients with a colon cancer can already have an additional cancer in their colon, colonoscopy is routinely recommended to identify whether a second cancer is present in the colon prior to surgery. During a colonoscopy, a long flexible tube that is attached to a camera is inserted through the rectum, allowing physicians to examine the internal lining of the colon for polyps or other abnormalities. Patients are given medication to minimize discomfort. The physician may perform a biopsy in order to collect samples of suspicious tissues or cells for closer examination.
  • Ultrasound: Ultrasound is a technique that uses sound waves to differentiate tissues based on varying tissue density. Ultrasound can be used transdermally (through the skin), transrectally (using a small probe inserted into the rectum) or intraoperatively (during surgery or during colonoscopy, which is called endoscopic ultrasound). Transrectal or endoscopic ultrasound may be used in conjunction with CT or MRI scans to help with staging.

Precision Cancer Medicine Testing for Colon Cancer

The purpose of precision cancer medicine to define the genomic alterations in the cancers DNA that are driving that specific cancer. Cancer used to be diagnosed solely by a visual microscopic examination of tumor tissue and all patients received the same chemotherapy. Precision cancer medicine utilizes molecular diagnostic & genomic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

By testing an individual’s colon cancer for specific unique biomarkers doctors can offer the most personalized treatment approach utilizing precision medicines.

Genetic Mutations

Not all colon cancer cells are alike. They may differ from one another based on what genes have mutations. Molecular testing is performed to test for certain genetic mutations or the proteins they produce because the results can help select treatment including newer precision cancer medicines designed to attack specific colon cancer cells with specific genetic mutations.

  • EGFR: The epidermal growth factor receptor (EGFR) is involved in cellular growth and replication. Some colon cancers produce too much EGFR and this leads to more rapid growth of the cancer. Some medicines specifically target EGFR and the spread of cancer can be reduced or delayed.
  • The RAS Genes: KRAS and NRAS are a family of proteins found in cells that when mutated promote cancer cell growth. An estimated 40–50% of colorectal cancers contain these genes. Some colon cancer treatments don’t work if the RAS gene is abnormal. If cancer has a KRAS or NRAS mutation drugs that inhibit cancer cell growth and survival by targeting a protein known as the EGFR are ineffective. Cancers lacking these genetic mutations are referred to as “wild type”.[2],[3],[4]
  • BRAF: BRAF is also a gene that signals cells to divide. Patients with mutant BRAF genes generally have a poorer prognosis (chance of survival and worse side effects) but may benefit from treatment with a precision cancer medicine.[5]
  • PIK3CA: While somewhat new, a growing number of clinicians are testing for mutant PIK3CA genes; particularly in patients who have early-stage colorectal cancer. There is some suggestion that aspirin use may help decrease the risk of recurrent colorectal cancer in patients with early stage disease and PIK3CA mutation.[6]
  • Microsatellite Instability High (MSI-H) MSI-H is a DNA abnormality found in about 15% of colon cancers. It is most often found in tumors associated with genetic syndromes like Lynch syndrome but can also occur sporadically. MSI-H is what “happens” when the genes that regulate DNA function don’t work correctly. These DNA regulating genes, known as Mismatch Repair Genes (MMR), work like genetic “spell checkers.” When problems occur in these spell-checking MMR genes, it means that areas of DNA start to become unstable. A high frequency of instability is called MSI-H. Patients with MSI-H tumors may respond differently to certain treatment. It is important to test colon cancers for this trait because it can help determine if the colorectal cancer is related to an inherited family syndrome.[4]
  • Carcinoembryonic Antigen (CEA) is a protein that may be higher in colorectal cancer patients. High levels of CEA may indicate that cancer is present or a treatment is not working. Low levels may indicate that the body is responding to a treatment.[4]

OncoType DX is a test that may help guide treatment decisions for patients with Stage II colon cancer. This test estimates the risk of cancer recurrence by evaluating the activity of certain genes in a sample of tumor tissue.(4) Risk of recurrence can vary greatly among patients with stage II colon cancer, and adjuvant (post-surgery) therapy is not routinely recommended for all patients with Stage II colon cancer, but may be considered for high-risk patients.[7]

Treatment information concerning colon cancer is categorized and discussed by the stage and presence or absence of specific biomarkers. In order to learn more about the most recent information available concerning the treatment of colon cancer, select the appropriate stage.

Stages of Colon Cancer

Stage I: Cancer is confined to the lining of the colon.

Stage II: Cancer may penetrate the wall of the colon into the abdominal cavity or other adjacent organs but does not invade any local lymph nodes.

Stage III: Cancer invades one or more of the local lymph nodes but has not spread to other distant organs.

Stage IV: Cancer has spread to distant locations in the body, which may include the liver, lungs, bones or other sites.

Recurrent/Relapsed: Colon cancer has progressed or returned (recurred/relapsed) following initial treatment.

Screening and Prevention of Colon Cancer

Colorectal cancer is the second leading cause of cancer death in the United States and strikes both men and women

The good news is that earlier detection of colorectal cancer through screening, coupled with improved treatment, has led to better colorectal cancer survival. Mortality rates have declined by almost three percent per year since 1998.[1]

The chance of an individual developing cancer depends on both inherited genetic factors as well as environmental or behavioral factors. By understanding what factors can increase the risk of colorectal cancer, you may be able to take steps to reduce your risk or to detect the cancer at an early stage.

Hereditary Factors

People with a family history of colorectal cancer are at increased risk for the disease, but risk is particularly elevated to people with certain inherited genetic conditions. Familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC; also called Lynch Syndrome) each greatly increase the risk of colorectal cancer. FAP and HNPCC account for a relatively small percentage (5-10%) of all colorectal cancers, but people with these conditions have a high lifetime risk of colorectal cancer, and often develop cancer at a much younger age than other people.

HNPCC is the most common type of hereditary colorectal cancer, and results from inherited mutations in genes involved in DNA mismatch repair.[2] In individuals with HNPCC, the average age at diagnosis of colorectal cancer is about 45 years. Other cancers that are more common in HNPCC families include cancers of the endometrium (the lining of the uterus), ovary, small intestine, ureter, and renal pelvis.

FAP results from inherited mutations in the adenomatous polyposis coli (APC) gene. People with FAP tend to develop numerous colorectal polyps, and polyps may occur as early as the preteen years.

All people with a family history of colorectal cancer should discuss their history with their physician in order to identify the optimal approach to surveillance and prevention. Screening may need to begin at a very early age for some people.[1],[8]

Other Factors

Inflammatory Bowel Disease (IBD): The two major types of inflammatory bowel disease—ulcerative colitis and Crohn’s disease—substantially increase the risk of colorectal cancer. An estimated 10-15% of deaths among people with IBD are due to colorectal cancer.[9] Because of this increased risk, people with IBD often undergo earlier and more frequent colorectal cancer screening.

Diet: Many aspects of diet have been studied in relation to colorectal cancer, often with mixed results. Dietary factors that have been reported to increase the risk of colorectal cancer include red meat and alcohol[10] Research suggests that consideration of an individual’s overall dietary pattern may also be important. A study of more than 76,000 women, for example, found that a diet rich in fruits, vegetables, legumes, fish, poultry and whole grains was linked with a lower risk of colon cancer (but not a lower risk of rectal cancer) than a diet high in red and processed meats, sweets, and refined grains.[11]

Obesity: Obesity has consistently been linked with an increased risk of colon cancer in men.(11,12) The extent to which obesity influences colon cancer risk in women is less clear, although larger waist circumference has been linked with increased colon cancer risk (but not rectal cancer risk) in both men and women.[12],[13]

Smoking: Studies of the link between tobacco and risk of colorectal cancer have been inconsistent. A pooled analysis of the Women’s Health Initiative studies found an increased risk of rectal cancer among smokers, but no increased risk of colon cancer.(14,15) Some previous studies, however, have reported a link between smoking and colon cancer.

Prevention of Colon Cancer

We may not be able to completely eliminate our risk of developing colorectal cancer, but there are steps that we can take to reduce our risk.

Diet: Eating a diet rich in fruits, vegetables, and whole grains may reduce the risk of colorectal cancer in addition to providing other health benefits. Since red meat and alcohol may increase the risk of colorectal cancer, these should be consumed in moderation (if at all). Finally, since obesity may increase the risk of colorectal cancer, it’s important to eat a diet that allows you to achieve or maintain a health body weight.

According to the International Agency for Research on Cancer (IARC), eating processed meat products can increase a person’s risk for developing colorectal cancer.(16) Processed meat is classified as meat that has been salted, cured, fermented, or smoked to add flavor or preserve the meat. These meats include ham, bacon, sausages, corned beef, hot dogs, canned meat, and beef jerky. Red meat includes beef, veal, pork, mutton, lamb, or goat. The IARC report does not mean that everyone who eats processed or red meat will develop CRC, nor does it mean that not eating these meats will eliminate an individual’s risk of developing CRC. Under no circumstances does the report suggest that individuals who do not eat processed meat should forego screening for CRC with colonoscopy or other tests. However reducing red meat consumption and substituting it with other alternatives like chicken and fish is likely to be beneficial.

Exercise: Studies suggest that regular physical activity reduces the risk of colon cancer.[17],[18],[19] Exercise may also reduce the risk of rectal cancer, but results for rectal cancer have been somewhat mixed.

Talk with your doctor before starting an exercise program. If your doctor decides that it’s appropriate for you, you may benefit from following exercise guidelines such as those provided by the American Cancer Society.(20) Developed for the general population (and not specifically for cancer survivors), the guidelines recommend that adults engage in at least 30 minutes of moderate-to-vigorous physical activity on five or more days per week. A longer duration of exercise (45 to 60 minutes) may provide additional benefits.

Moderate-intensity activity includes brisk walking and cycling on level terrain. Vigorous activity includes cycling or walking up hills and jogging.

Detection and Treatment of Precancerous Polyps: For cancers such as breast cancer, screening does not prevent the development of the cancer; rather, screening detects the cancer at an early stage when treatment is most likely to be successful. In the case of colorectal cancer, however, screening can sometimes prevent the development of cancer by identifying precancerous polyps. Removing these polyps can prevent the later development of cancer.

Non-steroidal Anti-inflammatory Drugs (NSAIDS): NSAIDS are used to reduce inflammation and pain; they include drugs such as aspirin and ibuprofen. Studies have suggested that NSAIDS reduce the risk of colorectal cancer.(21)The potential benefits of regular use of these drugs, however, must be weighed against the potential risks. In 2007, the U.S. Preventive Services Task Force (USPSTF) recommended against routine use of aspirin or other NSAIDS for the prevention of colorectal cancer in individuals at average riskof colorectal cancer.[22]

The following points contributed to this decision:

  • • While higher doses of aspirin appear to reduce the risk of colorectal cancer, lower doses of aspirin do not. Higher doses of aspirin increase the risk of gastrointestinal bleeding, and aspirin has also been linked with an increased risk of hemorrhagic stroke.
  • • Similarly, while there is some evidence that non-aspirin NSAIDS may reduce the risk of developing colorectal cancer, these drugs increase the risk of gastrointestinal bleeding and kidney problems. In addition, the class of NSAIDS known as COX-2 inhibitors has been linked with an increased risk of cardiovascular problems.

The USPSTF notes, however “These recommendations do not apply to patients with a personal history of colorectal cancer or other conditions that put them at high risk for the disease.” It is also important to note that these recommendations do not alter previous recommendations about the use of low-dose aspirin in people at increased risk of cardiovascular disease.

Patients at high risk for colorectal cancer as a result of personal or family history may wish to talk with their doctor about steps they can take to reduce their risk. A study of people with hereditary non-polyposis colorectal cancer (HNPCC) found that daily aspirin use cut the risk of colorectal cancer by roughly half.[23]

Calcium: Calcium may provide a modest colorectal cancer benefit. One study showed that patients taking 1200 mg of calcium daily demonstrated a 20% reduction in colorectal adenoma formation and a 45% reduction in advanced adenoma formation.[24] Physicians surmise that a reduction in adenoma formation would lead to a reduction in cancer rates. Furthermore, calcium and Vitamin D may work synergistically to decrease adenoma formation.

Vitamin D: Vitamin D is a fat-soluble vitamin that comes from dietary supplements, foods such as fortified milk and cereal, certain kinds of fish (including salmon, mackerel, and tuna), and exposure to sunlight. Vitamin D is hypothesized to play a role in the prevention of some types of cancer, including colon cancer. According to results from two large studies – the Health Professionals Follow-up Study and the Nurses’ Health Study – individuals with higher blood levels of vitamin D may have a reduced risk of developing colon cancer.[25]

Preventive surgery: Preventive surgery may be recommended for some people at very high risk of colorectal cancer, such as those with FAP. Surgery is performed to remove the colon (and sometimes the rectum and other organs as well) before cancer develops.

Screening and Early Diagnosis Of Colon Cancer

For many types of cancer, progress in cancer screening has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have symptoms of cancer.

Screening is crucial for the prevention and early detection of colorectal cancer. The American Cancer Society currently recommends that people at average risk of colorectal cancer begin being screened for colorectal cancer at the age of 50. Screening may need to begin at a much earlier age for people with a personal or family history of adenomatous polyps, FAP, HNPCC, colorectal cancer, or chronic inflammatory bowel disease.

Several screening strategies are currently available. These include the fecal occult blood test (FOBT), flexible sigmoidoscopy, colonoscopy and double contrast barium enema. The frequency of screening depends on the method. In general, FOBT is performed every year, sigmoidoscopy is performed every five years, and colonoscopy is performed every 10 years. Individuals interested in colorectal cancer screening should discuss the options with their physician in order to determine the most appropriate procedure.

According to recommendations from the U.S. Preventive Services Task Force (USPSTF), routine colorectal cancer screening should continue until the age of 75.[26] Patients over this age may wish to talk with their physician about the need for continued screening.

Fecal Occult-Blood Test (FOBT): The fecal occult-blood test checks for hidden blood in the stool. Recently, results from an 18-year study indicated that annual or biannual FOBT could significantly reduce the incidence of colorectal cancer. If positive, this test indicates the presence of bleeding polyps and the need for further screening, such as colonoscopy. The further screening tests allow the identification and removal of polyps, which results in a reduced incidence of colorectal cancer.

Fecal Immunochemical Test (FIT): Fecal immunochemical tests are a newer type of fecal occult-blood test. Unlike traditional FOBT, FIT does not require drug or dietary restrictions on the part of the patient.

DNA stool test: This newer screening procedure involves looking for abnormal DNA in stool samples. Changes in DNA occur as tumors develop in the colon. The tumors shed cells into the intestine, which makes it possible to detect the abnormal DNA cells in stool samples.[27]

Flexible Sgmoidoscopy: During this procedure, a physician uses a lighted tube to look inside the rectum and the lower part of the colon (sigmoid colon) for polyps or areas suspicious for cancer. The physician may perform a biopsy in order to collect samples of suspicious tissues or cells for closer examination. This is an outpatient procedure that does not require sedative anesthesia or pain medication. There are no or few complications associated with this procedure.

Colonoscopy: During this procedure, a longer flexible tube that is attached to a camera is inserted through the rectum, allowing physicians to examine the internal lining of the colon and rectum for polyps or other abnormalities. The physician may perform a biopsy in order to collect samples of suspicious tissues or cells for closer examination. This is a more difficult procedure than sigmoidoscopy to perform, requiring anesthesia or heavy sedation, but it allows the entire colon (sigmoid colon, descending colon, transverse colon, and ascending colon) and rectum to be viewed. Significant complications occur in 0.1-0.3% of patients or less.[26],[27]

Double-contrast barium enema: A chalky substance called barium is inserted through the rectum and into the colon and rectum. The patient then undergoes x-rays of the colon and rectum so that the physician can evaluate the area for polyps or other abnormalities. The barium helps open the colon so that the x-rays are more detailed and clear.

While these screening strategies help to monitor for the development of adenomatous polyps and colorectal cancer, other tests exist which may allow physicians to identify patients who are at risk for the development of colorectal cancer.

Predictive genetic testing: If your history suggests that your family has HNPCC or FAP, your doctor may discuss genetic testing with you. If you undergo genetic testing and are found to carry one of the HNPCC or FAP gene mutations, there are steps that you can take to manage your cancer risk.

Virtual colonoscopy: In virtual colonoscopy (also called CT colonography), spiral CT scanners scan the entire colon to produce a 3-D image. The procedure allows for the complete visualization of the colon more quickly and less invasively than with conventional colonoscopy, although patients who have polyps detected will still need to undergo conventional colonoscopy to have the polyps removed. Virtual colonoscopy is a promising new technique, but more research may be needed before it becomes a standard screening procedure for colorectal cancer.

References

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[3] Amado RG, Wolf M, Peeters M et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. Journal of Clinical Oncology. 2008;26:1626-1634.

[4] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology.™ Colon Cancer. V.3.2008. © National Comprehensive Cancer Network, Inc. 2008. NCCN® and NATIONAL COMPREHENSIVE CANCER NETWORK® are registered trademarks of National Comprehensive Cancer Network, Inc.

[5] abstracts.asco.org/199/AbstView_199_194502.html

[6] Liao X, Lochhead P, Nishihara R, et al. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. New England Journal of Medicine. 2012; 367: 1596-1606.

[7] O’Connell M, Lee M, Lopatin M et al. Validation of the 12-gene colon cancer recurrence score (RS) in NSABP C07 as a predictor of recurrence in stage II and III colon cancer patients treated with 5FU/LV (FU) and 5FU/LV+oxaliplatin (FU+Ox). Paper presented at: 2012 Annual Meeting of the American Society of Clinical Oncology; June 1-5, 2012;Chicago,IL. Abstract 3512.

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[8] Friedenreich C, Norat T, Steindorf K et al. Physical activity and risk of colon and rectal cancers: the European prospective investigation into cancer and nutrition. Cancer Epidemiology Biomarkers & Prevention. 2006;15:2398-407.

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