What is Colorectal Cancer?
In cancer, cells in the body grow out of control. Healthy cells develop mutations in their DNA, leading them to divide abnormally and form a tumor. When this cancer begins in the lower digestive tract, the colon or the rectum, it is known as colorectal cancer (or colon cancer, for short).
Colorectal cancer occurs in both men and women of all races and ethnic groups, who are older than 50 years. Colorectal cancer used to be the second leading cause of cancer deaths in the United States, but an increase in screening for early signs of the disease and, perhaps, lifestyle changes have decreased the incidence significantly in the last 10 years. The overall lifetime risk of developing colorectal cancer is about 1 in 23 for men and 1 in 25 for women, although individual risk factors such as family history may affect the overall risk.
In 2017, when the latest figures were calculated, 141,425 new cases of colorectal cancer were reported, with 52,547 deaths. For every 100,000 people, there were 37 new cases and 14 deaths, compared with 56 new cases and 21 deaths 20 years ago, a decrease of over 30 percent.
Screening can also find cancers at an early stage, when the cancers are easier to treat, greatly increasing survival. The causes of colon cancer are not fully understood. In the majority of cases (about 75%), there are no known predisposing conditions, although research is providing some answers. Sometimes, abnormal growths called polyps form in the colon or rectum, and these may turn into cancers. People with a personal or family history of polyps or colorectal cancer are at greater risk, although only a small percentage of colon cancers have been linked to inherited genes. Screening can identify these precancerous polyps so that they can be removed. Chronic inflammation in the gut, such as Crohn’s disease or ulcerative colitis, predisposes to colorectal cancer.
Other risk factors include older age. Ninety percent of colon cancers are found in people older than 50 years, which affects recommendations for screening. African Americans are at greater risk that people of other backgrounds. Diabetes and obesity are linked to increased risk of colon cancer. Diet may play some role, although these are merely associations. A typical Western diet, low in fiber and high in fat and calories, high in red and processed meat or lacking fruit and vegetables, might contribute to colon cancer incidence. Regular physical activity may reduce the risk of colon cancer, while smoking and heavy alcohol consumption increases the risk. Finally, radiation therapy or previous abdominal cancers increases the risk of colon cancer.
If colon cancer develops, many treatments are available to help control it, including surgery, radiation therapy, and drug treatments such as chemotherapy, targeted therapy and immunotherapy.
Colorectal Cancer Symptoms
Colon cancer may cause no symptoms at first. Colorectal polyps and colorectal cancer may not cause problems, explaining why regular screening for colorectal cancer is so important.
When symptoms do appear, they will depend on the tumor’s size or where it is in the large intestine. Symptoms may include:
Colorectal Cancer Screening and Diagnosis
Screening tests are carried out of groups of people before they have any symptoms. Screening tests tend to provide a plus or minus answer. By contrast, diagnostic tests are carried out on individuals who have symptoms or a positive screening test, and provide a lot of information about the cancer.
The most effective way to reduce colorectal cancer risk is to be screened regularly, especially for people aged 50 to 75 years old. People older than 75 may also be screened upon medical advice. Sometimes, younger people with predisposing risk factors undergo screening, such as those with inflammatory bowel disease (Crohn’s disease or ulcerative colitis), a family history of polyps or certain genetic syndromes (familial adenomatous polyposis (FAP) or hereditary non-polyposis colorectal cancer, also known as Lynch syndrome). Screening can prevent colorectal cancer because it finds the cancer at an early stage when removal is possible or treatments work best.
Colorectal cancers most often begin as precancerous polyps (abnormal growths) in the colon or rectum. These may be found in the colon years before invasive cancer develops, causing no symptoms. Stool tests are used to detect either blood (from injured intestinal surfaces) or cancer-derived mutant DNA from cancer cells. Stool tests can be done on a frequent schedule, especially where there are risk factors. Direct examination using a non-surgical procedure such as colonoscopy, sigmoidoscopy or CT colonography and MRI scans may find precancerous polyps so they can be removed before they turn into cancer. These examinations are performed every 5-10 years, unless there are medical indications for greater frequency.
Other screening tests may become available soon. One of these is called liquid biopsy. A small blood sample is tested for the presence of whole or fragmented cancer cells, or mutated DNA from cancer cells, using very sophisticated laboratory tests. In other cancers, the liquid sample may be urine, spinal fluid or lung fluid. At the moment, liquid biopsies are used to track treatment, following rises and falls in the concentration of cancer cells or DNA in the samples.
Diagnostic tests are used to determine the type of colon cancer and whether it has spread to other parts of the body.
Types of cancer in the colon and rectum
A small piece of the tumor (a biopsy) is examined by a pathologist to determine what type of tumor is present.
- The most common colorectal cancers are adenocarcinomas. These start in cells that make the mucus which lubricates the inside of the colon and rectum. Some sub-types of adenocarcinoma, such as signet ring and mucinous, may have a worse prognosis (outcome) than other subtypes of adenocarcinoma.
- Much less common types of gastrointestinal tumors can also start in the colon and rectum. These include carcinoid tumors starting in the hormone-producing cells in the intestine, stromal tumors starting in the wall of the intestine, lymphomas that arise from cells of the immune system in intestinal lymph nodes and, rarely, sarcomas that begin in the blood vessels and muscles in the wall of the colon and rectum.
Changes in the DNA of colorectal cancer cells may predict which patients have a higher risk of colorectal cancer recurrence after treatment. These genetic drivers can cause a cancer cell to behave differently and grow more rapidly, increasing the aggressiveness of the tumor. These new genetic tests might help to tailor treatment by indicating whether more or less, or a different, treatment are required to control the cancer.
After the diagnosis of colon cancer, tests are carried out to determine the extent (stage) of your cancer. Staging helps determine what treatments are most appropriate for you. Staging tests may include imaging procedures such as abdominal, pelvic and chest CT scans. However, colon cancer surgery may be required to accurately stage the tumor.
The stages and substages of colon cancer are designated using by the Roman numerals from 0 to IV, as follows.
- Stage 0: the cancer that is limited to the lining of the inside of the colon, and is sometimes called carcinoma in situ or intramucosal carcinoma.
- Stage I: the cancer has started invading the wall of the intestine.
- Stage IIA: The cancer has grown into the outermost layers of the colon but has not grown through them.
- Stage IIB: The cancer has grown through the wall of the intestine, but has not spread to other tissues or organs, including the nearby lymph nodes or distant sites.
- Stage IIC: The cancer has passed through the colon wall and has either attached to or grown into nearby tissues, but has not reached local lymph nodes or distant tissues.
- Stage III: the tumor has spread locally and may have invaded nearby organs. Cancer cells may be present in local lymph nodes, but there is no spread to distant sites.
- Stage IV: The tumor is advanced, having spread (metastasized) to distant organs such as the lung or liver.
Colorectal Cancer Treatments
The four main treatment options are surgery, radiation, medication and supportive care. The choice of treatments depends on individual circumstances, including the location of the cancer, its stage and other health concerns.
The aim of surgery is to remove the cancer completely, or to reduce its size to improve the performance of other treatments. The stage and location of the cancer is important in deciding on surgery.
Surgery for early-stage colon cancer
If the colon cancer is very small, a minimally invasive surgical approach may be used. There are many options.
- Removing polyps during a colonoscopy (polypectomy). For small, localized tumors completely contained within a polyp and in a very early stage, complete surgical removal is possible during a colonoscopy.
- Endoscopic mucosal resection. For larger polyps, special instruments are used during colonoscopy to remove the polyp and a small amount of the inner lining of the colon, in a procedure called endoscopic mucosal resection.
- Minimally invasive surgery (laparoscopic surgery). Polyps that cannot be removed during a colonoscopy may be removed using laparoscopic surgery. The operation is performed through several small incisions in the abdominal wall, inserting instruments with attached cameras that display the colon on a video monitor. In the same operation, samples may be taken from lymph nodes near where the cancer is located.
Surgery for more advanced colon cancer
If the cancer has grown into or through the colon wall, more drastic surgery may be required.
- Partial colectomy. The part of your colon that contains the cancer, along with a margin of normal tissue on either side of the cancer, is removed. It is often possible to reconnect the healthy portions of your colon or rectum. Partial colectomy can usually be performed laparoscopically, as a minimally invasive procedure.
- Colonostomy. If it is not possible to reconnect the healthy portions of the colon or rectum, an ostomy may be required. An opening is created in the wall of the abdomen and the remaining part of the bowel is attached. This allows the elimination of stool into a bag fitted on the outside of the opening. Colonostomy may be temporary to allow the colon or rectum to heal after surgery. However, sometimes the colonostomy has to be permanent.
- Lymph node removal. Nearby lymph nodes are usually also removed during colon cancer surgery and tested for cancer.
- Surgery for metastasis. In certain specific cases where the cancer has spread only to the liver or lung, but overall health is otherwise good, other localized surgical procedures may be applied to remove the cancer. Chemotherapy is often given in conjunction with surgery and can lead to long term cancer-free survival.
Surgery for very advanced cancer
If the cancer is very advanced or the overall health of the patient is very poor, surgery may be performed to relieve symptoms such as a blockage of your colon, bleeding or pain. Such surgery does not cure cancer, but instead relieves signs and symptoms of colorectal cancer.
Radiation therapy involves the use of high energy beams like X-rays and protons to destroy cancer cells. Radiation is toxic to rapidly dividing tumor cells. Radiation may be used to reduce the size of a large tumor before surgery to make its removal easier. Radiation can be used on its own (without surgery) to relieve pain and other symptoms caused by a large tumor. Alternatively, radiation can be combined with chemotherapy.
The major approaches to medication (treatment with drugs) are chemotherapy, targeted therapy and immunotherapy.
Chemotherapy, literally to use of chemicals as therapeutic agents, is the oldest form of cancer treatment. Chemotherapy is the use of drugs to destroy cancer cells. Most chemotherapeutic drugs stop cells dividing. Since cancer cells are dividing rapidly out of control, the use of these drugs, known as anti-proliferative agents, is logical. Howevr, normal cells in the body also divide, such as the skin, lining oft the intestine and ahir follicles, Hence, chemotherapeutic agents can have a range of side effects, most notable (although trivial) being hair loss.
Chemotherapy is often given before an operation to shrink a large cancer, increasing the chance of its removal at surgery. Chemotherapy for colon cancer is usually given after surgery if the cancer is large or has spread to the lymph nodes. In this way, chemotherapy may kill any cancer cells that remain in the body and help reduce the risk of cancer recurrence. Patients with low-risk stage III colon cancer may receive a shorter course of chemotherapy after surgery, an effective approach to reduce the side effects compared with the traditional course of chemotherapy.
Chemotherapy can also be used to relieve symptoms of colon cancer that can’t be removed with surgery or that has spread to other areas of the body. Sometimes it’s combined with radiation therapy.
Some examples of chemotherapeutic drugs used to treat colon cancer are 5-Fluorouracil, Capecitabine, Irinotecan and Oxaliplatin.
Targeted drug therapy
The biochemical processes (pathways) are altered by genetic mutations, leading to accelerated cell growth or resistance to drugs and drug-induced cell death. Newer drugs target these mutated pathways, causing the cancer cells to die. Such drugs, because they are specifically targeted, generally have fewer side effects than chemotherapeutic agents. Targeted drugs are usually combined with chemotherapy. Targeted drugs are typically reserved for people with advanced colon cancer.
Some examples of targeted drugs are Irenotecan (inhibits an enzyme called topoisomerase I), Bevacizumab and Ramucirumab (which block the effects of a cell growth factor).
Immunotherapy harnesses the immune system to attack and destroy the cancer. Remarkably, the immune system may not attack a tumor because the cancer cells produce proteins that ‘block and blind’ immunity. Hence, cancer cells protect themselves from immune recognition and destruction. Immunotherapy is aimed at removing this blockade interfering with immune attack.
Immunotherapy is usually reserved for patients with more advanced cancers, and works better in some patients than others. Tests are available to determine which patients will benefit from each form of immunotherapy.
Two examples of immunotherapeutic agents are Nivolumab and Pembrolizumab. Cancer cells can produce a molecule that prevents the immune system from killing them. Both of these agents neutralize that molecule, allow for the cancer cells to be killed.
Palliative care aims to improve the quality of life for people with cancer and their families. This form of care may be delivered along with curative or other treatments, to provide relief from pain and other symptoms of a serious illness.
Palliative care is provided by a team of doctors, nurses and other specially trained professionals that work with the patient, their family and their doctors to provide an complementary extra layer of patient support. When palliative care is used along with all of the other appropriate treatments, people with cancer may feel better and live longer.
Survival Rates for Colorectal Cancer
Survival rates give an estimate of how long people with a certain stage of colon cancer may survive. This is never a personal assessment although survival rates do provide an understanding of the possible success of treatment of colorectal cancers. These estimates are retrospective, using data from the last 5-20 years. Because new treatments are more effective than those used a decade ago, outcomes are improving with time.
A relative survival rate compares patients with the same type and stage of cancer to people in the overall population. If the 5-year relative survival rate for Stage II colorectal cancer is 75%, then, on average, 75% of patients with Stage II cancer are expected to be alive 5 years after their diagnosis compared with people who don’t have that cancer.
The American Cancer Society provides survival figures based on how far the cancer has spread, namely:
There is no sign that the cancer has spread outside of the colon or rectum.
The cancer has spread outside the colon or rectum to nearby structures or lymph nodes.
The cancer has spread to distant parts of the body such as the liver, lungs, or distant lymph nodes.
This is not exactly the same as clinical staging (Stages 0-IV) but is related. These are called SEER (Surveillance, Epidemiology, and End Results) stages of patients first diagnosed with cancer between 2010 and 2016.
5-year relative survival rates for colon and rectal cancer
Survival rates are grouped based on how far the cancer has spread, but age, overall health, how well the cancer responds to treatment, whether the cancer started on the left or right side of the colon, and other factors can also affect your outlook. Note, again, that these figures are based on old data, and treatments have improved over the last 5-10 years.
|SEER Stage||5-year relative survival rates|
|Colon Cancer||Rectal Cancer|
|All SEER stages combined||63%||67%|