Colorectal cancer (CRC) is no longer a taboo subject. Public education has boosted awareness of the disease — and has patients over age 50 lining up for colonoscopies. (Many will remember former Today Show host Katie Couric having a colonoscopy on air to promote screening after her husband died of colon cancer.) The good news is that deaths due to CRC have been declining since the mid-1980s thanks to improved screening, earlier detection, and better therapies.¹ To help ensure that the downward trend continues, nurses should be knowledgeable about the risks of developing CRC, screening methods, pathophysiology and staging, and treatment strategies.

CRC is the third most common type of cancer in the United States, Canada, and Europe. In the United States, an estimated 112,300 cases of colon cancer will occur this year, with an additional 41,000 cases of rectal cancer. CRC is the second leading cause of cancer deaths in the United States, after lung cancer.^2,3 Incidence of CRC is about equal among men and women. Of all racial groups, African Americans have the highest risk of developing and dying of CRC.

Age is a major risk factor. Diagnoses of CRC increase steadily after age 40. More than 90% of people diagnosed with CRC are over 50, with the average age at diagnosis of 72.⁴ Other risk factors include family history of colon cancer, Crohn’s disease, ulcerative colitis, polyps, cigarette smoking, a diet high in animal fats, obesity, and genetic abnormalities.

Two identified genetic mutations linked to CRC involve the hereditary nonpolyposis colon cancer gene and the adenomatous polyposis coli gene. About 2% of CRC cases are caused by changes in the HNPCC gene, and those affected are usually diagnosed at younger ages. APC mutations are rarer and lead to familial adenomatous polyposis, characterized by large numbers of polyps in the colon and rectum that if untreated, usually develop into cancer by the time the person turns 40. Genetic testing can detect these mutations. Vigilant screening and surveillance is essential in people who test positive or have affected family members.

An additional risk factor for CRC is the presence of benign polyps in the colon and rectum that are allowed to grow. Routine colonoscopy can identify and remove such polyps, making the procedure an important part of prevention.

Most colorectal cancers are adenocarcinomas, cancers that arise in epithelial cells. In CRC, tumors arise in the glandular epithelium of the colon or rectal mucosa. As they grow, tumors invade deeper tissues, starting with the muscularis mucosa (a thin layer of muscle supporting the mucosa), the submucosa (supportive tissue below the muscle), and eventually, if not treated, the muscularis propria (the larger muscle responsible for peristalsis).

Cells gone awry

Cancer usually develops after a series of genetic occurrences. Benign polyps, or adenomas, undergo genetic changes that promote carcinogenesis. During carcinogenesis, cells become less differentiated as they multiply, and rules that normally regulate cellular division and function no longer apply. Growth is unchecked, prompting cells to invade surrounding tissues and eventually spread to other areas.

Most colon cancers metastasize initially to the liver, but may also spread to other areas, including the brain, lungs, or bone. Rectal cancers are more likely to spread to the lung.⁴ Metastatic cancer may be present at diagnosis or may appear as recurrent disease. Cancer that spreads to other organs is still colon cancer, not a new cancer arising within another organ.

For people over age 50 without a family history of CRC, the American Cancer Society recommends routine screening with a fecal occult blood test annually plus flexible sigmoidoscopy every five years or a colonoscopy every 10 years.² Colonoscopy is preferable; the entire colon is visualized, and polyps can be removed during the procedure.

Debate continues about appropriate follow-up after polyp removal during colonoscopy, but increased surveillance is essential. The American Cancer Society recommends that a patient have a colonoscopy at the very least every five years after polyp removal. Those with a strong family history or positive genetic testing are encouraged to have colonoscopy at least every one or two years, starting at age 21, increasing the frequency to every year at 40.

In early stages of CRC, symptoms may be absent. Some people may experience constipation or diarrhea, black tarry stools, or stools containing fresh blood. Changes in shape of stool may be noted. In more advanced cases, patients may experience abdominal bloating or pain. At times, patients may present with anemia from an unknown source. Fatigue and weight loss are more advanced signs of CRC.

Definitive diagnosis is made by tissue examination in pathology. The tissue may be from polyps removed during routine screening or liver biopsy in the case of metastatic disease. Tissue noted positive for adenocarcinoma is graded for degree of aggressiveness, and tests are done to stage the cancer. Pathologic grade refers to the level of differentiation (maturation) of the cancer cells. The less differentiated the cells, the higher the grade and the more aggressive the cancer. Pathologic grades range from Grade 1 (well differentiated) to Grade 4 (poorly differentiated).

Staging refers to the extent of disease; the higher the stage, the more invasive the tumor. Several staging systems are used, with a range from Stage 0 (cancer present in the innermost lining of the colon) to Stage 4 (metastatic disease).

Once pathology determines that adenocarcinoma is present, other staging exams rule out metastatic disease. CAT scans of the chest, abdomen, and pelvis are routine in the staging workup, and results are a major determinant in planning treatment. If symptoms of bone metastasis are present, such as pain or pathologic fracture history, a bone scan will be obtained.

Another important part of the workup is the measurement of the blood tumor marker carcinoembryonic antigen. But CEA is not specific for colon cancer; it may be elevated in other nonmalignant conditions. But a baseline, presurgical CEA may be a tool in monitoring for recurrent disease after treatment.⁵

The options

Depending on the extent of disease during staging, treatment may include some or all of the following: surgery, chemotherapy, radiation, biotherapy, or, in rare cases, no treatment or hospice. In advanced disease, patients will receive symptom and pain management and hospice care.

In Sage 0 or 1, the cancer may be removed by colonoscopy in a procedure called a polypectomy. But few cases are Stage 0 or 1 at diagnosis. In colon cancer, the more typical surgery is removal of part of the colon (partial colectomy). In some cases, removal of the cancer and surrounding lymph nodes is performed through laparoscopy, which is as effective as standard abdominal surgery.⁷ Only rarely are permanent colostomies required following partial colectomy although temporary stomas may be needed.

Rectal cancer requires different surgical techniques, determined by location of the cancer. Cancers in the lower rectum require an abdominalperineal resection in which the lower rectum and anus is removed. This necessitates a permanent colostomy. Cancers higher in the rectum may not require colostomy as an anastomosis between the sigmoid colon and the lower rectum and anus may be possible.

Patients with Stage 4 disease frequently require surgery to prevent bowel obstruction (palliative debulking). Some metastatic lesions may also be removed in the interest of prolonging survival and improving quality of life. If small enough in size and number, hepatic lesions can be treated with surgical resection, radiofrequency ablation (using heat to destroy lesions), cryosurgery (freezing), or embolization (blocking blood flow to the tumor). Lung lesions that fit criteria regarding number and size may also be surgically removed in an effort to prolong survival and improve quality of life. If metastatic lesions exist in more than one area, surgery is rarely an option given its invasiveness and the likelihood that the cancer is widespread.⁷ These patients receive systemic chemotherapy.

Radiation therapy is rarely used in colon cancer, but it’s standard in rectal cancer treatment, used in combination with chemotherapy both neoadjuvantly (before surgery to remove the cancer) and adjuvantly (after surgery). The goal of neoadjuvant therapy is to reduce the size of the cancer (downstaging) to minimize the surgical risk. Adjuvant therapy is used after the cancer is surgically removed to treat remaining microscopic disease and prevent recurrence. Intraoperative radiation therapy can be used to treat advanced, recurrent, or inoperable rectal cancer. It’s also used when it’s difficult to attain adequate disease-free margins during surgery.

Radiation adverse effects depend on the dose and area (field) radiated. Diarrhea, skin irritation, and bladder irritation (radiation-induced cystitis) are common in rectal cancer. Most toxicities resolve several weeks after treatment ends. In some cases, chronic adverse effects occur, such as irritation of the rectum (proctitis) and irritation of the colon (radiation colitis).7

The mainstay

Chemotherapy after surgery is the mainstay treatment in more advanced colon cancers. The agents used depend whether the cancer is Stage 2, 3, or 4 and whether the patient has had chemotherapy before.

It is standard of care to offer adjuvant therapy in Stage 3 disease (lymph node invasion). But in Stage 2, guidelines are less clear; toxicities related to chemotherapy may outweigh the benefits. Therefore, it is recommended that adjuvant chemotherapy for Stage 2 disease be given only in clinical trials.⁸

The most recently approved regimen for treating newly diagnosed Stage 3 patients is a combination called FOLFOX, using leucovorin (folinic acid), 5-fluorouracil 5FU (Adrucil), and oxaliplatin (Eloxatin). 5FU has been the backbone of CRC chemotherapy for 40 years. Both monthly schedules and every-two-week continuous infusion schedules have been used; the current standard practice in the adjuvant setting is the de Gramont schedule, calling for 5FU, leucovorin, and oxaliplatin on Day 1 of each two-week cycle, followed by a 46-hour continuous infusion of 5FU. Because of the continuous infusion, patients require a central venous access device, which they manage at home via a portable pump. Central venous access is also necessary because of the irritant properties of oxaliplatin.

An oral chemotherapy agent, capecitabine (Xeloda), most commonly used in metastatic disease, was recently approved for the adjuvant setting. Once absorbed, capecitabine is converted to the active form of 5FU by thymidine phosphorylase, an enzyme abundant in cancer cells. Capecitabine combined with oxaliplatin is called the XELOX regimen.¹

First-line treatment for newly diagnosed Stage 4 disease normally consists of FOLFOX plus bevacizumab (Avastin), a monoclonal antibody. Another frequent drug combination is FOLFIRI, which includes 5FU, leucovorin, and irinotecan (Camptosar). Other options include the monoclonal antibody cetuximab (Erbitux), given alone or in combination with irinotecan, and most recently panitumumab (Vectibix), a fully humanized monoclonal antibody. Multiple options are now available to prolong survival for patients with metastatic cancer, and many patients take part in clinical trials.⁹

Monoclonal antibodies are man-made proteins that bind to specific proteins or receptors on the surface of cancer cells. Cetuximab and panitumumab target the epidermal growth factor receptor; bevacizumab targets the vascular endothelial growth factor receptor. Both receptors exist in large numbers on cancer cells and play a role in cancer growth. Additional targeted therapies are in development.¹⁰

Chemotherapy may also be used in patients with unresectable liver metastases through a hepatic arterial infusion. This way, higher doses can be delivered directly to the tumors since the drug is delivered into the hepatic artery, limiting exposure to the systemic circulation. An implantable pump delivers the chemotherapy, generally a drug called floxuridine (FUDR). Hepatic arterial infusion risks include risks from pump placement surgery, thrombus within the hepatic artery, movement of the catheter, and leakage of drug from the artery.¹¹ Clinical trials are under way to establish whether hepatic arterial infusion provides a true benefit in treating liver metastases.

The most common adverse effects of chemotherapy are myelosuppression with resultant anemia, thrombocytopenia, and neutropenia; nausea; vomiting; diarrhea; fatigue; and hair loss. Neutropenia (low neutrophils) and thrombocytopenia (low platelets) are of great concern in cancer care. Patients who have severe neutropenia must be closely monitored as signs and symptoms of infection are rarely present because of the absence of immune cells. The Oncology Nursing Society recommends that patients be instructed to contact their clinic if they have a temperature of 100.5 F or higher; blood cultures may be required.¹²

The risk of sepsis in severely neutropenic patients is high, and a delay in recognizing symptoms can be disastrous. Thrombocytopenia is also of concern as platelets may fall below 20,000 per mm3 in rare cases. Platelet transfusions may be given for severely low levels or if symptoms such as nosebleeds, bleeding of the gums, or petechiae occur.

Many patients complete chemotherapy without serious myelosuppression thanks to biologic therapies that help prevent severe neutropenia and anemia. Yet nurses should always educate patients and caregivers about possible complications and ways to minimize risks. Using strict hand-washing techniques and avoiding crowded places are prevention strategies during episodes of neutropenia. Using soft-bristle toothbrushes and electric razors are examples of preventive strategies for bleeding.

Relief from vomiting

The antiemetic arsenal is larger than ever, and the association of chemotherapy with protracted vomiting no longer exists. With the first chemotherapy dose, aggressive antiemetic measures are needed to prevent chronic and anticipatory anxiety, nausea, and vomiting.¹³

Diarrhea is a potentially life-threatening toxicity of CRC chemotherapy. Irinotecan is the agent most likely to induce diarrhea. In most cases, frequent loperamide (Imodium) dosing controls the diarrhea, but occasionally stronger medications are required. The recommended regimen for chemotherapy-induced diarrhea is 4 mg of loperamide at the first sign of diarrhea, followed by 2 mg every two hours until the patient is diarrhea-free for at least 12 hours.¹⁴ Instruct patients to maintain adequate hydration during any episodes of diarrhea. Patients should be told to report diarrhea that does not improve despite the use of antidiarrheal medications. IV fluid replacement may be indicated.

Another concern is diarrhea accompanied by neutropenia. Breaks in the colonic mucosa and irritation from frequent bowel movements can quickly lead to overwhelming sepsis. Thus, patients should be vigilant about taking their temperature, and nurses must treat fevers as serious events warranting evaluation.

Colon cancer therapies may also cause mucositis (inflammation and possible ulceration of the lining of the mouth, throat, or GI tract). This is most frequent in the mouth and oropharynx, but can occur in the intestinal tract. Watch for yeast infection and instruct patients on oral hygiene. Liquid medications can help prevent pain and infection if mouth sores occur.

During chemotherapy, neurotoxicity can arise as direct or indirect damage to the CNS, peripheral nervous system, or cranial nerves. Oxaliplatin is the agent most likely to cause neuropathy, a dose-limiting toxicity. ADLs should be assessed before each cycle to assess for neuropathy. Watching patients button a shirt or fill out a questionnaire helps clinicians visualize the toxicity and helps patients describe how it may be impairing function. Dose delays or reductions may be needed to prevent irreversible toxicity.

Oxaliplatin can cause laryngopharyngeal dysesthesia, brought on by cold. Patients describe a feeling of tightening in the throat and an inability to breathe when this occurs. About 10% of patients experience it, and it is most likely to occur within the first seven days after the infusion.²

Patients receiving oxaliplatin should avoid cold foods and beverages and standing in front of air conditioners and freezers. Reassure patients that this toxicity is time-limited and should resolve when therapy is over.

Hand-foot syndrome is a toxicity seen in patients receiving 5FU or capecitabine. This painful toxicity is characterized by tingling, redness, and tenderness in the palms or soles. Often chemotherapy doses need to be modified or delayed to prevent it from worsening. Severe cases include blistering, swelling, pain, and eventual desquamation. Nurses can recommend OTC emollients, such as Udder Cream, Biafine, or Aveeno, for comfort and skin integrity.

Patients taking capecitabine should be educated about possible adverse effects and report them immediately. This is specially important because patients taking capecitabine are not seen in the clinic as often as infusion patients, so clinicians have fewer chances to ask them about adverse effects.²

While less toxic than many chemotherapy agents, biologic agents, including monoclonal antibodies, do have risks. They may trigger severe allergic reactions during dosing; treating RNs must be prepared to deal with an anaphylactic event. Adverse effects related to cetuximab include acniform skin rashes, thickening of the skin, nail changes, fatigue, and headache for several days after infusion. Bevacizumab may cause GI perforation and bleeding, hypertension, proteinurea, headaches, and diarrhea. Panitumumab can cause lung scarring and skin rashes, some severe.¹⁰

More than physical effects

Nurses can address the psychosocial concerns of patients and families, such as possible loss of life, financial problems, role status, and sexuality. Support includes referral to support groups and other community resources and perhaps to a cancer counselor or social worker.

Someday oncologists may be able to individualize cancer treatment based on a patient’s genetic risk of recurrence and the molecular characteristics of cancer cells. Until then, nurses can help by promoting cancer screening and healthy lifestyles, and providing clinical and psychosocial support to patients and families coping with CRC.