Gardner's syndrome

Objectives: At the conclusion of this activity the participant should be able to:

1. Identify risk factors for colorectal cancer.

2. State the screening recommendations for individuals at average risk.

3. Differentiate clinical presentation of colorectal cancer based on tumor location.

4. Identify treatment modalities for colon and rectal cancer.

5. Describe quality of life issues for individuals with colorectal cancer.

Directions: Read the article carefully. Return the answer sheet (or a copy) printed at the end of the article and fill out all sections carefully. Mail to the address provided with the appropriate fee. Certificates will be mailed upon successful completion of both the post-test and evaluation. You must score at least 70% to pass. Should you fail the test you will be notified and offered an opportunity to retake the test. All retakes will require an additional fee.

Contact Hour and Accreditation: This 1.4 contact hour activity has been approved by the North Dakota Nurses Association which is has been accredited as an approver of continuing education in nursing by the American Nurses Credentialing Center (ANCC). Contact hours are valid through August 15, 2005.

Colorectal Cancer

Colorectal cancer is the third most common cancer in men and women in the United States. Despite awareness about risk factors and primary and secondary prevention, it remains the second most frequent cause of cancer deaths. Because colorectal cancer often shows few symptoms until the advanced stages of the disease, nurses can play a pivotal role in identifying patients at risk, providing information and promoting screening and early detection tests to decrease mortality and morbidity.

Incidence

Americans have about a 5.9 % lifetime risk of being diagnosed with colorectal cancer, with the incidence increasing significantly beginning at 40 years of age. In 2003, an estimated 147,500 new cases of colorectal cancer will be diagnosed and approximately 57,100 deaths will occur in the United States. In Nebraska, 1,100 new cases of colorectal cancer will be diagnosed and 400 deaths will occur (Jemal et al, 2003). The overall incidence of colorectal cancer is similar for both men and women, however rectal cancer occurs more often in men than in women. The incidence is higher in industrialized regions such as North America, Europe and Australia than in Asia, Africa, and South America (Saddler & Ellis, 1999).

The incidence also varies significantly by race and ethnicity. In blacks, the incidence of colorectal cancer has increased by 30% since 1973 and is higher than in whites (Pazdur, 1999). Incidence in the Alaska Natives population is over four times as high as rates in the American Indian population (New Mexico) for both men and women. After Alaska Natives, the next highest rates are among the Japanese, black and non-Hispanic white populations. These are followed by Chinese, Hawaiians, and white Hispanics; and then Filipinos, Koreans and Vietnamese. In each racial/ethnic group, incidence rates for cancers of the colon and rectum among women are lower than those among men (National Cancer Institute, 1996).

Mortality patterns by race and ethnicity are similar to those for incidence. However, the mortality rates among white non-Hispanic and black men and women, and among Hawaiian men, appear disproportionately high (National Cancer Institute, 1996). The differences in incidence rates among various races and ethnic groups may be explained by lifestyle or environmental factors, especially diet and exercise. Several studies have shown that migrants to the United States from Japan and other countries where rates of colorectal cancer are lower than in the U.S. have higher rates than those who remain in their native country. Also, first and second generation American offspring from these migrant groups develop these cancers at rates reaching or exceeding those of the white population in the United States (National Cancer Institute, 1996).

Risk Factors

The specific causes of colorectal cancer are unknown, however a number of factors are associated with an increased risk of developing colorectal cancer (Table 1).

Age

As with most malignancies, the development of colorectal cancer is associated with aging. The risk of developing colorectal tumors becomes significant starting at age 40 and increasing until the eighth decade. More than 90% of individuals are over the age of 50 at the time of diagnosis (Ries et al., 2000).

Diet

Both national and international studies have shown a clear association between colorectal cancer and specific dietary habits. The Western diet, known for being high in fat, cholesterol and red meat, and lower in fruits, vegetables and fiber content, has been linked to an increased risk of colorectal tumors. People living in the industrialized countries in North America, Northwestern Europe and Australia frequently consume this type of diet. Animal fats and cholesterol contribute to the production of secondary bile acids, which exerts a carcinogenic effect. Fiber is an important dietary component because it decreases the contact time of carcinogenic substances with the mucosa in the bowel (Wynder, Reddy & Weisburger, 1992).

Personal History of Intestinal Polyps

Adenomatous colonic polyps are small outgrowths from the inner lining of the colon and are different from other types of polyps that do not present an increased risk for the development of colorectal cancer. Adenomatous polyps may take from seven to twelve years to progress from normal mucosa to adenoma to cancer (Rawl, Menon, & Champion, 2002). They are common in obese and individuals with a high-fat consumption and in certain families. It is estimated that 19% to 41% of the general population will develop adenomatous polyps, although about 10% of these individuals will also have a first-degree relative with a history of colorectal cancer (Jessup, 1997). These dysplastic adenomas are precancerous. and are classified as villous, tubulovillous, and tubular. Villous lesions only comprise 10% of adenomas but are more likely to be malignant. Tubular adenomas account for 75% of adenomas but comprise only 5% of malignancies. Patients with multiple polyps have twice the risk for cancer than those with a single polyp (Baker, 2001). The overall risk of adenomatous polyps progressing to cancer is approximately 2% to 5%, with polyp size being a major risk factor. Polyps less than 0.5 mm are unlikely to progress to malignancy, while those greater than 2 mm have been shown to have about a 46% malignancy rate over a 10-year interval (Markowitz & Winawer, 1997).

Inflammatory Bowel Disease

Individuals with inflammatory bowel disease, such as ulcerative colitis or Crohn's disease, have a higher than normal incidence of colorectal cancer. The risk of colorectal cancer in patients with ulcerative colitis is associated with the duration of active disease, going from around 3% in the first decade of disease to more than 30% in the third decade. Other important factors include the extent of bowel involvement, age at onset, and severity of disease. The risk of colorectal cancer in patients with Crohn's disease is lower than in patients with ulcerative colitis (Chase, Hoff & Pazdur, 1998).

Hereditary Syndromes

Several hereditary syndromes, accounting for about 6% of colorectal cancers, are associated with a high risk of colorectal cancer. Familial adenomatous polyposis (FAP) is an. inherited autosomal dominant trait that results in the development of hundreds to thousands of polyps throughout the colon and rectum in late adolescence. FAP accounts for approximately 1% of all colorectal cancers. The lifetime risk of cancer in persons with FAP approaches 100% by the age of 50 (Skibber, Minsky, & Hoff, 2001). Hereditary nonpolyposis colorectal cancer (HPNCC), also known as the Lynch syndrome, is an autosomal dominant inherited condition characterized by the development of colorectal cancer at an average age of 45 years. The lifetime risk of colorectal cancer approaches 80% in individuals carrying a mutation in an HNPCC gene. Individuals affected usually have one or a few adenomatous polyps, but not polyposis. HPNCC occurs as type A (Lynch type I) and type B (Lynch type II). Type Ais familial, site-specific nonpolyposis colon cancer. Type B is nonpolyposis colon cancer in association with other cancers, such as breast, endometrial, stomach or ovarian. HNPCC is relatively common, accounting for 2% to 5% of all colorectal cancer cases. Surveillance has been shown to reduce the risk of colorectal cancer and other associated cancers (Lynch et al., 1993). Clinical clues that may signal the presence of HNPCC include (1) colon cancer in a first- or second-degree family member; (2) colon cancer diagnosed under the age of 50 years; (3) multiple generations affected; (4) multiple primary cancers, including endometrial, stomach, ureteral/renal pelvis, and small bowel; (5) the predominance of right-sided cancer; and (6) ovarian cancer (NCCN, 2003).

Hereditary flat adenoma syndrome (HFAS), a variation of FAP, consists of multiple flat adenomas that have an increased risk of becoming cancerous. Other genetic premalignant polyposis syndromes, including Turcot syndrome and Gardner's syndrome are associated with a high risk of colorectal cancer (Pazdur, 1999).

Personal or Family History of Colorectal Cancer

An estimated 10% of Americans have a first-degree relative with colorectal cancer, which is known to increase their individual risk two to three times (Jessup et al., 1997). Even without an identified genetic predisposition, having more than one relative with colorectal cancer, or having colorectal cancer at an early age increases the risk for other family members to develop colorectal cancer. A personal history of colorectal cancer increases the risk of developing a second primary colon cancer or other malignancy, particularly at the site of anastomosis from the previous surgery (Pazdur et al, 1999). Women with a history of breast, endometrial, or ovarian cancer also have an increased risk of developing colorectal cancer (Rawl, Menon & Champion, 2002).

Lifestyle Factors

A sedentary lifestyle without at least moderate physical activity is associated with an increased risk of colorectal cancer. Heavy alcohol consumption and smoking also increases the risk of colorectal cancer (Rawl, Menon & Champion, 2002).

Clinical Presentation

The majority, 90 to 95% of colorectal cancers are moderately or well-differentiated adenocarcinomas (Pazdur et al., 1999). Mucinous adenocarcinoma is a histologie variation characterized by large amounts of extracellular mucus in the tumor. Signet-ring cell carcinomas contain large quantities of intracellular mucin displacing the nucleus. It is generally associated with a worse prognosis. Squamous cell carcinomas, carcinoid tumors, and adenosquamous and undifferentiated carcinomas can also be observed in the colon and rectum. Squamous cell carcinomas are more commonly seen in the rectum, while carcinoid tumors tend to originate in the cecum and appendix. Other tumors, such as sarcomas, non-Hodgkin's lymphomas, and small cell tumors, are very rare (Skibber, Minsky & Hoff, 2001),

The presenting symptoms of colorectal cancer vary depending on tumor location (Figure 1). Generally, changes in bowel habits are not displayed with right-sided (ascending colon) lesions; the stool is of a liquid consistency at that point in its passage through the colon, and bleeding that occurs will appear as dark blood because it is old by the time it appears in the stool. Altered stool caliber, constipation, gas, and abdominal cramping are more typical in left-sided (descending colon) lesions. Tumors that occur in the rectum produce similar symptoms; however, tenesmus (urgency) and bright red bleeding are classic (Hoebler, 1997; Skibber, Minsky & Hoff, 2001).

Prevention and Detection

Approximately 75% of all colorectal cancer occurs in people without any known predisposing factors and therefore are considered to be at average risk. Fifteen to 20% of high-risk individuals have a family history of colorectal cancer but no genetic predisposition (Saddler & Ellis, 1999). Despite evidence that prevention and early detection improves survival outcomes, less than 40% of adults age 50 and older reported having had a recent screening exam for colorectal cancer. In addition, the 2001 Behavioral Risk Factor Surveillance System survey found that men were slightly more likely than women to have reported a sigmoidoscopy or colonoscopy within the preceding five years. Less than one in four men and women reported having had a FOBT using a home kit (Smith, Cokknides, & Eyre, 2003). It is obvious that tremendous opportunities exist to prevent colorectal cancer through primary and secondary prevention measures or to diagnose colorectal cancer, at an early stage when it can be effectively treated.

Primary Prevention

Primary prevention involves implementation of specific health behaviors or practices to prevent the onset of a specific disease or condition. Approximately 50% of colorectal cancers can be prevented by modification of health-related behaviors including lack of physical exercise, diet, and alcohol and tobacco use that increase the risk of developing colorectal cancer (Tomeo et al, 1999). Recent evidence has demonstrated the protective role of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin when used regularly reduces the number and size of colorectal polyps. A protective role has also been ascribed to calcium salts, calcium-rich foods and the use of exogenous estrogens in women. These factors may decrease colon cell turnover and reduce the cancer-promoting effects of bile acid and fatty acids. More evidence is necessary before routine recommendation of aspirin, NSAIDs, or calcium supplements as preventative agents. Several studies have suggested that retinoids (vitamin A), carotenoids (vitamin A precursors), ascorbic acid (vitamin C), tocopherol (vitamin E) and selenium have antioxidant properties that may help to prevent the development of cancers by neutralizing toxic free radicals; further investigation remains warranted (Hawk, Limburg, & Viner, 2002).

Secondary Prevention and Early Detection

Secondary prevention includes efforts to identify and treat asymptomatic persons who have already developed risk factors or premalignant disease that has not become clinically apparent. Colorectal cancer can be prevented with the detection and removal of precancerous adenomatous polyps. Early detection is the identification of early-stage disease and is associated with a reduction in disease-related mortality. By educating the public, primary caregivers, and managed care companies about the risk factors, symptoms and signs of colorectal cancer, and the importance of regular screening and follow-up, approximately 30,000 lives could be saved each year (American Gastroenterological Association, 1997). Colorectal cancer screening procedures currently available include the fecal occult blood test, flexible sigmoidoscopy, digital rectal exam, colonoscopy and double-contrast barium enema. Although each procedure differs in accuracy, cost and risk, each has been shown to be efficacious and cost effective. The recommended type and frequency of screening methods is dependent on the presence of individual risk factors (Table 2: Screening Recommendations). Fecal occult blood tests (FOBT) are inexpensive but have been associated with false-positive and false-negative results. Most colonie polyps and more than 50% of all colorectal cancers are undetected by this test because they are not bleeding at the tune of the test. Therefore, the American Cancer Society (ACS) and the National Comprehensive Cancer Network (NCCN) do not recommend using the FOBT alone for colorectal screening (NCCN, 2000). However, annual or biennial fecal occult blood testing has demonstrated a significant reduction in the incidence of colorectal cancer (Mandel et al, 2000). Digital rectal examination (DRE) is easy to perform and can detect lesions in the anus (up to 7 cm from the anal verge). Due to the inability to examine the full length of the colon, the ACS and NCCN recommend using the DRE together with other tests and examinations such as the FOBT and flexible sigmoidoscopy (NCCN, 2000). Flexible sigmoidoscopy is an invasive procedure that examines the distal colon up to the splenic flexure, varying from 30-60 cm. Sigmoidoscopy has been reported to have a sensitivity of 85% for detecting polyps. It is important to note that a sigmoidoscopy does not examine the proximal colon. Recent findings indicate that about 50% of persons with a polyp detected by sigmoidoscopy will have proximal tumors (Rawl, Menon, & Champion, 2002). Colonoscopy is an invasive procedure than examines the entire colon and can be used to obtain biopsy specimens of adenomas and carcinomas and to excise adenomatous polyps. It is estimated to have a sensitivity rate of 95%. Colonoscopy has been used primarily as a diagnostic, rather than a screening test. The arguments against using it as a screening test are lack of randomized clinical trial data and cost. About 60% of tumors are found in the distal colon and can be detected by sigmoidoscopy. Recent evidence has shown that more polyps are being found in the proximal colon and would be missed with traditional FOBT and sigmoidoscopy (Rawl, Menon & Champion, 2002). Following these reports, Medicare changed its policy and now reimburses for colonoscopy screening for colorectal cancer (Trowbridge & Burt, 2002). Double contrast barium enema (DCBE), also called an air contrast barium enema, is a series of x-rays of the colon and rectum. The x-rays are taken after the patient is given an enema with a white, chalky solution that contains barium to outline the colon and rectum on the x-rays. A false-negative rate associated with the DCBE ranges from 2% to 18% because of misreadings, poor preparation, or difficulties detecting smaller lesions. A DCBE should be viewed as complementary to colonoscopy (Chase, Hoff & Pazdur, 1998).

Diagnostic Evaluation

A diagnostic evaluation for patients suspected of having colorectal cancer should include a detailed family history to exclude the possibility of a high-risk genetic predisposition to colorectal cancer and other malignancies. Other pertinent history includes frequency and consistency of stools, rectal bleeding, appetite, weight loss or gain, and the presence or absence of abdominal or rectal pain. The physical exam may be unremarkable in the early stage of colorectal cancer. The presence of cachexia with a history of weight loss implies advanced disease. A digital rectal exam should be performed to determine the presence of a distal lesion. A complete lymph node examination should be conducted to exclude distant metastases and a thorough pelvic examination should be performed to evaluate for the presence of gynecologic malignancy or abnormality (Baker, 2001).

In the absence of an obstructive lesion, the large intestine should be examined thoroughly for the presence of polyps or carcinomas. Colonoscopy is preferable to a barium enema because it allows for the biopsy and removal of lesions. Imaging studies are helpful in determining the extent of disease. Computed tomography (CT) or spiral CT scans are useful in determining the spread of tumor to adjacent organs, to assess lymph node involvement and to detect liver, lung or other distant metastasis. Magnetic resonance imaging is a sensitive method for detecting lesions small than 2 cm in diameter, especially those in the pelvis and rectum. CT portography is used to detect small hepatic metastases 1 to 2 cm in diameter (Saddler & Ellis, 1999). A positron emission tomogram (PET) scan is the only test that does not depict just anatomy. Using a glucose solution that contains a radioactive atom, areas with increased metabolism, such as tumors are identified. The role of PET scans in colorectal cancer is still under investigation (NCCN).

Transrectal ultrasound can assist with determining tumor depth and nodal involvement with at least 60% to 80% accuracy in patients with rectal cancer (Baker, 2001).

Laboratory tests should be performed based on the patient's comorbidities or the presence of metastatic disease, such as liver function tests. A complete blood count frequently reveals a microcytic anemia. Tumor markers for colorectal cancer include CEA (carcinoembryonic antigen) and CA 19-9. CEA is expressed in the mucosal cells of the colon and rectum and is the most commonly used marker for gastrointestinal cancers. It is overexpressed by adenocarcinomas, especially those of the colon and rectum. More than 90% of colorectal cancers produce CEA and in patients with advanced disease, 85% will have an elevated CEA. However, an abnormal serum level is not specific for colon cancer or a malignancy. Elevated CEA levels can also occur in smokers, liver dysfunction, renal failure, peptic ulcer, pancreatitis, inflammatory bowel disease and hepatitis (Macdonald, 1999). CEA levels are often used in monitoring effectiveness of treatment and to determine the presence of residual disease or recurrence. An elevated CEA by itself is a poor prognostic indicator in patients with primary colorectal cancer (Baker, 2001).

Staging and Prognosis

The pathologic stage of the tumor at the time of resection is the single most important indicator of prognosis (Pazdur et al, 1999). Stage indicates depth of tumor penetration into and through the intestinal wall, regional lymph node involvement and absence or presence of metastases. Tumors are considered invasive if they extend through the muscularis layer and into the submucosa. Tumors may spread via direct extension to adjacent structures such as the peritoneal wall or spread via the lymph and vascular systems to distant sites. Spread to the liver occurs in half of all colon cancers because of the proximity of the liver in the capillary network (Baker, 2001). The second most common site of metastases is the lungs, present in 10% of patients. Other reported sites, in order of prevalence, include the bones, brain, kidneys, and adrenal glands (Pazdur et al, 1999). Two primary staging systems currently are in use: the widely used TNM system and the Dukes' classification. Many colorectal specialists will stage a patient's cancer by both methods (Griffin-Sobel, 2001). Other factors to consider in determining prognosis are age at diagnosis, duration of symptoms, level of CEA prior to surgery, site of disease, histologie characteristics of the tumor, perineural invasion, bowel obstruction or perforation, and blood or lymphatic invasion (Saddler & Ellis, 1999).

Colorectal cancer is potentially curable if detected at an early stage and is associated with a 5-year survival rate of about 90%. Regional involvement has a 5-year survival rate of about 65%, with only a 9% five-year survival rate for distant metastasis. Unfortunately, only 34 to 38% of patients have localized disease at the time of diagnosis whereas 35 to 38% of patients have regional disease, and 19 to 24% have metastatic disease (Jemal et al, 2003).

Treatment

Surgery - Colon Cancer

Surgical resection is the primary treatment for colorectal cancer and is the standard treatment for early-stage disease (stage I or early stage II) with close follow-up. The goal of surgery is to eliminate the disease in the colon and surrounding tissues. The location of the tumor, the blood supply and lymph node patterns will determine the extent of resection. Right Hemicolectomy is indicated for cecal, ascending, and hepatic flexure lesions. Lesions in the cecum comprise approximately 22% of colorectal cancers and tumors of the right colon comprise up to 15% of primary colorectal cancers. Major complications include injury to the duodenum or ureter and bile acid deficiency. Right Radical Hemicolectomy is indicated for transverse colon or hepatic flexure lesions in addition to those removed in a right hemicolectomy. Major complications include ureteral or duodenal injury, bile acid deficiency, anastomotic dehiscence and diarrhea.

Transverse Colectomy is indicated for midtransverse lesions of the colon. Lesions in the transverse colon comprise approximately 8% of colorectal malignancies. The major complication is anastomotic dehiscence. Left Hemicolectomy is indicated for lesions of the left colon. Tumors in the descending colon comprise 5% of primary colorectal cancers. The major complication associated with this procedure is anastomotic dehiscence. Low Anterior Resection is indicated for lesions of the sigmoid and proximal rectum. Sigmoid lesions comprise 35% of colorectal cancers. Anastomotic dehiscence and bowel ischemia are the major associated complications.

Subtotal Colectomy is indicated for multiple synchronous lesions and lesions of the distal transverse colon. Complications include anastomotic dehiscence, diarrhea and perineal excoriation (Baker, 2001; Saddler & Ellis, 1999; Sheldon, 2002). In the early 1990s, there was considerable interest in using laparoscopic techniques instead of open resection for colorectal cancer treatment. Two areas of concern have surfaced with the use of laparoscopic resection: (1) port site recurrence, including trocar sites, and (2) limitations with resection. Large multicenter randomized trials are currently being conducted to determine the efficacy and long-term survival outcomes related to laparoscopic resections (Kockerling et al., 2000).

Surgery - Rectal Cancer

The successful management of rectal cancer includes cure, local control, return of normal bowel function, preservation of anorectal sphincter function and conservation of urinary and sexual function. Local control is very important as up to 25% of patients dying of rectal cancer will have local recurrence only, and another 50% will have local recurrence in addition to distant metastases (O'Brien, 2002). Abdominoperineal resection is recommended for rectal tumors located in the lower third of the rectum within 7 to 8 cm of the anal verge. This procedure involves a transabdominal resection of the rectum with colostomy formation in combination with a transperineal excision of the anus and distal rectum. Complications include ureteral injury, urinary dysfunction, wound infections, stomal complications and sexual dysfunction. Low anterior resection is indicated for tumors in the distal sigmoid to the middle rectum (between 8 and 12 cm from the anal verge). A resection of the middle rectum with a primary anastomosis is performed providing sphincter preservation. Complications include anastomotic leak, abscess, wound infection, stricture, and irregular bowel function (Baker, 2001; Saddler & Ellis, 1999). Total mesorectal excision includes the mesorectum that surround the rectum and ensures the distal margins are at least 2 cm. This procedure, introduced in the 1980s has shown excellent results with a 10-year local recurrence rate of 4% and a 10-year disease-free survival rate of 78%. The risk of anastomotic dehiscence is considerable, frequently requiring a temporary colostomy (Baker, 2001; O'Brien, 2002).

Radiation Therapy for Colon Cancer

Because the development of distant metastases is more common than local recurrence with colon cancer and currently it is not possible to predict who is at high risk for local recurrence, the role for radiation therapy as adjuvant treatment in colon cancer is unclear. Whole abdominal radiation therapy, from the diaphragm to the pelvic floor, is of limited use because of the excessive toxicity with required doses. Local control is improved with 5-FU based chemotherapy combined with whole abdominal radiation therapy. However, a significant number of these patients develop metastases in the liver (Giri et al, 1993). Current studies are examining the use of adjuvant radiation therapy and chemotherapy in high-risk patients with stage III disease.

Radiation Therapy for Rectal Cancer

Preoperatively, radiation is delivered to decrease the risk of local recurrence, prevent the development of distant metastasis and reduce tumor size to permit sphincter-preserving surgery. Local recurrence is more common with rectal cancer because of the retroperitoneal location. Randomized trials have shown a significant decrease in local recurrence rates with preoperative radiation. Unfortunately it has not affected overall survival rates, development of metastasis or improved cure rates (Saddler & Ellis, 1999). Intraoperative radiation therapy can be used to treat advanced, recurrent, or inoperative rectal cancer. Typically, intraoperative radiation is used to treat rectal cancer if there is difficulty obtaining adequate disease-free margins. Some studies have demonstrated a lower rate of local recurrence as well as a prolonged survival of three years for persons with rectal cancer when intraoperative radiation therapy is used (Minsky, 1994). Postoperative radiation combined with 5-FU based chemotherapy for stage II and III rectal cancer increases both the disease-free interval and overall survival (GITSG, 1985) and is currently standard therapy. Current clinical trials are investigating the schedule of 5-FU during pelvic radiation, the optimal timing of surgery following radiation therapy, whether chemotherapy adds to the benefits of preoperative radiation, and preoperative versus postoperative adjuvant combined modality treatment (NCI, 2003).

Adjuvant Therapy for Colon Cancer

Until the late 1980s, the role of adjuvant therapy in colorectal cancer was unclear. Studies published in 1989 and 1990 showed for the first time the clinical benefit of 5-FU in the adjuvant setting. These initial studies used 5-FU in combination with levamisole and have demonstrated an improved survival rate (60% vs 36%) in surgically resected stage m patients receiving 5-FU/levamisole compared to surgery alone (Moertel, Fleming & Macdonald, 1990). In the last decade, studies of other 5-FU based regimens in combination with leucovorin have also shown efficacy in the adjuvant treatment of colorectal cancer (Wolmark, Rockette & Fisher, 1993). The current standard of care for stage HI colon cancer is six months of 5-FU plus leucovorin given in a variety of different doses and schedules. While the schedule does not appear to impact effectiveness, toxicities can be different with leukopenia and stomatitis more common with the 5-day low dose regimen and diarrhea more common in the weekly regimen.

While the evidence for the use of adjuvant chemotherapy in resected stage III colorectal cancer is clear, the role of adjuvant chemotherapy for localized, node-negative stage II dis ease is controversial. The results of a recent meta-analysis showed no significant different in overall survival between adjuvant treatment (82%) and observation (80%) in stage II colon cancer. The decision to use adjuvant chemotherapy in stage II colon cancer must be individualized, with other high-risk factors such as obstruction or perforation considered (MPACT2 Investigators, 1999).

Adjuvant Therapy for Rectal Cancer

The goal of adjuvant therapy in rectal cancer is not only to decrease the risk of distant metastases, but also to reduce the incidence of local recurrence. In the absence of nodal metastases, the local recurrence rates in rectal cancer are: stage I, 5-10%; stage II, 25-30%; and stage III, 50% or higher (Pazdur et al., 1999). In 1990 the NIH consensus conference recommended postoperative therapy for patients with stage II and III rectal cancers. The studies reviewed for the consensus revealed using combined modality treatment of postoperative pelvic radiation and 5-FU based chemotherapy showed a significant overall survival compared to surgery alone and a significant reduction in local recurrence and distant metastases (Steele, Augenlicht, & Begg, 1990). Neoadjuvant treatment of rectal cancers is increasing in interest. The main advantage is increase of surgical options for sphincter preservation. It also may decrease tumor seeding, and may be tolerated better and less toxic in the elderly. Current research has shown an improvement in local control without a significant impact on survival (O'Brien, 2002).

Treatment for Advanced Colorectal Cancer

Until recently, 5-FU and leucovorin was considered to be the first-line treatment for metastatic colorectal cancer. In 1996, irinotecan was approved for patients who had progressed after 5-FU-based therapy. Studies showed a response rate of 13% with a median survival of approximately 9 months. In addition, stabilization of progressive disease and palliative benefits were present (Conti, Kemeny & Saltz, 1996). Recent randomized trials to determine the efficacy of irinotecan as first-line treatment have shown response rates ranging from 39% to 49% in patients who received a combination of irinotecan, 5-FU and leucovorin. Median survival was 14.8 months to 17.4 months (Saltz, Cox & Blanke, 2000). Based on the favorable response rates, irinotecan is now approved for use in combination with 5-FU and leucovorin for first-line therapy for newly diagnosed metastatic colorectal cancer. Several new agents are currently under investigation for the treatment of colorectal cancer. Capecitabine, currently available for the treatment of metastatic breast cancer, is being explored for use in colorectal cancer. Early clinical trials report a higher response rate and better toxicity profile. Also under investigation is UFT, the combination of uracil plus tegafur (a 5-FU pro-drug). Two studies were recently completed comparing UFT with leucovorin and 5-FU with leucovorin for colorectal cancer. Preliminary results show an improved survival in patients treated with UFT plus leucovorin. In August 2002, the FDA approved the combination of oxaliplatin, 5-FU and leucovorin in the treatment of patients hose colorectal cancer recurred or progressed during or within six months following standard first-line treatment with irinotecan, 5-FU, plus leucovorin (Berg, 2003). In addition, an international phase III trial has recently demonstrated significant reduction in the risk of recurrence with the addition of oxaliplatin to standard chemotherapy for patients with locally advanced colorectal cancer (Mayer, 2003).

Targeted therapy is also showing promising results for advanced disease. IMC-C225 or cetuximab, is a monoclonal antibody that targets the epidermal growth factor. Preliminary clinical trial results for IMC-C225 in combination with irinotecan in patients with advanced colorectal cancer have shown favorable response rates (Sheldon, 2002). Researchers have recently reported that adding the experimental anti-angiogenesis drug bevacizumab, known as Avastin, to standard chemotherapy significantly improves survival for patients with metastatic colorectal cancer (Hurwitz, 2003).

For patients with metastatic disease, radiation therapy is used primarily for palliation and symptom management. Radiation therapy is used palliatively to treat symptoms such as pain, obstruction, and bleeding, as well as therapeutically to treat bone métastases and spinal cord compression.

Another area of increasing interest in the treatment of advanced colorectal cancer is liver-targeted therapies. The liver is the most common site of metastases for colorectal cancer. Approximately 25% of patients will have liver metastases at the time of diagnosis (O'Brien, 2002). Median survival for patients with liver metastases is only 3 years. Therapies targeted at liver metastases aim to intensity cancer treatment directly to the liver without affecting systemic complications. These techniques include cryosurgery, chemoembolization, radiofrequency ablation, alcohol injections and hepatic artery infusion. They may be used alone or in combination with other forms of treatment. The effectiveness of these treatments continues to be investigated (Berg & Lilienfeld, 2001; O'Brien, 2002).

Quality of Life Issues and Nursing Implications

Quality of life is a concept related to outcomes of cancer and cancer treatment. Traditional outcomes have included disease-free survival, mortality, morbidity, and relapse rates (King, Haberman, Berry et al., 1997). The experience as perceived by the patient is not included in these outcomes. Quality of life as evaluated by the patient has become an important outcome that fills this void. Because patients with cancer survive longer than in the past, the quality of that survival is an important outcome (Grant, 1999).

Quality of life is subjective, it is a personal evaluation of one's life and the level of satisfaction with that life (Nayfield, Hailey & McCage, 1990). A quality of life model used frequently in nursing studies is a four-dimensional model, which focuses on physical, psychological, social, and spiritual well-being. This model incorporates the nursing responsibilities to assess the patient's responses to illness, including not only disease aspects, but also the influence 6f family, interpersonal relationships, social factors, culture, and work (Ferrell, Grant, Vemuri & Rhiner, 1991).

Issues affecting the physical well-being for patients with rectal cancer treated surgically with sphincter-sparing resection or with abdominoperineal resection include dietary changes, incontinence, inability to control flatus, skin problems, sexual dysfunction and perineal discomfort. Psychological well-being is affected by changes in body image, depression, anxiety, and coping difficulties. Issues affecting social well-being involve returning to work, changes in style of clothing that can be worn, financial concerns and a decrease in participation in social, sexual and athletic activities. Spiritual well-being is influenced by the support received from religious beliefs, uncertainty about the future and changes in the meaning of life (Grant, 1999). Providing information on available resources such as the local American Cancer Society or other organizations can be beneficial and informative. Teaching the patient how to care for a stoma, providing information about potential complications and their treatment and giving information about the local ostomy support group are also important for restoration of quality of life.

Side effects of chemotherapy and radiation therapy also affect quality of life. Adjuvant chemotherapy may produce diarrhea, mucositis or stomatitis, myelosuppression, nausea, vomiting, anorexia, hair thinning, taste changes and skin and nail changes. Although the severity of these symptoms may vary depending on the chemotherapy regimen, patient education related to identification and treatment of symptoms and the importance of regular follow-up care is essential to maintain maximum quality of life during treatment. Radiation therapy is frequently accompanied by fatigue, anorexia, diarrhea, dysuria, and skin reactions such as perianal dermatitis. Assessment and treatment of skin problems is essential to preserve maximum quality of life and may require collaboration with an enterostomal therapy nurse or radiation oncology nurse to provide the correct skin care.

The patient with advanced or progressive disease needs assistance in achieving relief from pain, both physical and psychological. Relief of physical pain is often easier to accomplish. Fear, anxiety, depression, anger, and loneliness are often more challenging to alleviate. Frequently, the patient and family seek answers about how much time is left and what will it be like at the end. Despite the knowledge that no one can truly predict the tumor growth rate and the resulting duration of life, guidance can be provided. Palliative care can support the patient physically as well as emotionally and is very important in maintaining quality of life for as long as possible (Berg, 2003). To assist in decreasing morbidity and mortality from colorectal cancer, the nurse must have current knowledge about risk factors, prevention, screening and genetic counseling. Equally important is knowledge about surgical procedures, adjuvant treatment, and their impact on patients' quality of life. Equipped with this knowledge, the nurse can make an important contribution to the prevention, treatment, and care of patients with colorectal cancer.

This article is part of the efforts of the Lancaster County Crusade Against Cancer to increase awareness about colorectal cancer.

Post Test - Colorectal Cancer

1. People at average risk for developing colorectal cancer should begin screening at:

a. Puberty

b. 40 years of age

c. 50 years of age

d. 65 years of age

2. According to current colorectal cancer screening guide lines, people at average risk should be offered the following tests:

a. Fecal occult blood test (FOBT) annually; flexible sigmoidoscopy every 3-5 years

b. Barium enema annually

c. FOBT, CEA and digital rectal exam every 3-5 years

d. Colonoscopy every 5 years

3. All of the following are at an increased risk for developing colorectal cancer except:

a. Individuals with a family history of colorectal cancer

b. Individuals with inflammatory bowel disease

c. Women with a history of breast cancer

d. Individuals who eat a low-fat diet

4. The primary location for presentation of colorectal cancer:

a. Rectum

b. Left-sided or descending colon

c. Sigmoid colon

d. Right-sided or ascending colon

5. Patients with stage III colon cancer should be treated with the following:

a. No further therapy after surgical resection of the primary tumor

b. Radiation therapy alone

c. 5-fluorouracil plus leucovorin after surgical resection

d. Irinotecan therapy after surgical resection

6. Signs and symptoms of colorectal cancer in the ascending colon include:

a. Bloody stools, change in bowel habits

b. Tenesmus and bright red bleeding

c. Cramps, gas pains, nausea and vomiting

d. Liquid stools, melena, palpable mass

7. The most common site of metastasis:

a. Liver

b. Lungs

c. Bones

d. Brain

8. The most important indicator of prognosis is:

a. Age at diagnosis

b. Pathologic stage of tumor

c. CEA level

d. Perforation or bowel obstruction

9. The goals of preoperative radiation therapy in rectal cancer include all the following except:

a. Decrease risk of local recurrence

b. Reduce tumor size

c. Prevent development of metastasis

d. Eliminate need for adjuvant therapy

10. Which nursing care approach is essential in maintaining and improving quality of life for the patient with colorectal cancer?

a. Teaching the patient hands-on self care

b. Counseling the patient and family about treatment options

c. Obtaining a referral for a psychologist

d. Encouraging the patient to see a chaplain

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by Ruth Van Gerpen

MS, RN, OCN, Clinical Nurse Specialist

Bryan LGH Medical Center

Lincoln, NE

Copyright Alabama State Nurses' Association Dec 2004-Feb 2005
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