US Pharm. 2012;37(12):22-26.
ABSTRACT: In 2012, the American Cancer Society (ACS)
revised its guidelines for colorectal cancer screening. The guidelines
serve as a reference for recommended tests and schedules based upon risk
factors for developing colorectal cancer. Screening tests are
classified according to their ability to detect the presence of a cancer
or to identify a patient with polyps that may become cancerous. Some
tests, such as colonoscopy, require bowel preparation to cleanse the
visualized site and improve evaluation. Several products are available
for this purpose. If a patient is diagnosed with colorectal cancer,
treatment with a combination of surgery, radiation, and/or systemic
therapies can commence. Colorectal cancer is preventable, and adherence
to screening guidelines can help reduce its impact on patients’ lives.
The familiarity of pharmacists with these guidelines and their knowledge
of screening tests can serve as a valuable resource and as
encouragement for patients to follow ACS recommendations.
Guidelines for cancer screening have been available to practitioners
and patients for decades to broaden awareness of cancer symptoms and to
facilitate timely diagnosis and treatment. In June 2012, the American
Cancer Society (ACS) released updated guidelines for early detection of
colorectal cancer.1 This article will provide background
information on the pathology and treatment of colorectal cancer and
summarize the revised colorectal screening guidelines.
The ACS estimated that, in 2012, colorectal cancer would be diagnosed
in more than 103,000 Americans and would account for nearly 52,000
deaths.2 This ranks colorectal cancer as the third most
common type of cancer and the third leading cause of cancer death in the
United States.2 General risk factors for colorectal cancer
include age older than 50 years, history of hereditary intestinal
polyposis and nonpolyposis conditions, personal or family history of
colorectal cancer, history of inflammatory bowel disease (i.e.,
ulcerative colitis or Crohn’s disease), history of Streptococcus bovis bacteremia, use of ureterosigmoidostomy, and presence of type 2 diabetes.1,3
Lifestyle factors that may contribute to the development of colorectal
cancer include a diet high in animal fat, tobacco use, physical
inactivity, obesity, and heavy alcohol use.1 Night-shift work for 3 or more days per week for at least 15 years has been shown to have a weak link to colorectal cancer.3 Overall, the lifetime risk of developing colorectal cancer is estimated to be 1 in 18.4
Colorectal cancer arises in epithelial cells of the colon or rectum
when multiple cumulative genetic mutations alter cell processes that
normally restrict division, migration, and differentiation and confer
malignant proliferative, invasive, and metastatic characteristics upon
the cells.5 Once a tumor has gained malignant status,
continued genetic instability leads to further alterations that can
affect the cancer’s properties over time and impact sensitivity to
treatment. Some of these mutations can serve as tumor markers for
clinicians, such as activation of the latent gene encoding
carcinoembryonic antigen, which can be measured in the blood to monitor
treatment response or to detect recurrence.5
Most cases of colorectal cancer develop from polyps, growths that
protrude from the mucosal surface into the gastrointestinal (GI) tract
lumen.3 Three types of polyps occur: hamartoma (junior
polyp), hyperplastic mucosal proliferation (hyperplastic polyp), and
adenomatous polyp. Adenomatous is the only premalignant type, and fewer
than 1% of these polyps become cancerous. Adenomatous polyps are found
in approximately 30% of middle-aged patients and 50% of elderly
patients, which highlights the importance of proper screening to
identify affected individuals before the polyp becomes cancerous.
Factors affecting the probability of a polyp becoming cancerous include histologic features, size, and appearance.3
Adenomatous polyps may be tubular, villous, or tubulovillous, with
villous adenomas the most likely to be cancerous. Adenomatous polyps may
be either sessile (flat) or pedunculated (stalked), with sessile types
being more likely to progress to cancer. Finally, polyps greater than
2.5 cm are five times more likely to be cancerous than those less than
1.5 cm (10% vs. 2%). Overall, once an adenomatous polyp forms, it takes
at least 5 years of growth to reach clinical significance, suggesting
the need to initiate screening and perform routine follow-up evaluation
to identify polyps that are of concern before they become cancerous.3
As the developing polyp grows, it may extend into the muscular wall of
the colon, where it can invade nearby blood and lymph vessels and
thereby enable local or distant metastasis.1
The relatively slow progression of polyps into colorectal cancer
enables patients to take proactive steps to reduce the risk of cancer
and the impact it can have on their lives. Symptoms that should prompt a
visit to a physician include a change in usual bowel habits lasting for
more than a few days, a sensation of the need for a bowel movement that
is not relieved by having a bowel movement, intestinal cramping or
abdominal pain, prolonged weakness or fatigue, and unintended weight
loss.1 Upon further evaluation, a patient also may be found to have liver-enzyme elevations and iron-deficiency anemia.4
Most of these symptoms are vague in terms of what their cause might be,
likely causing many patients to fail to seek medical assistance.
However, the possibility that these symptoms may represent a malignancy
should be the impetus for an individual to seek a proper and prompt
Screening Tests and Bowel Preparation
The goal of colon cancer screening is to identify and remove polyps
in an asymptomatic individual before malignant transformation occurs or
to identify cancer early in the course of disease, when cure is most
likely.1 A variety of screening tests may be performed. These
tests may be categorized according to whether they can detect both
polyps and cancerous lesions (flexible sigmoidoscopy, colonoscopy,
double-contrast barium enema, CT scan of colon) or identify only the
presence of cancer (fecal occult blood test [FOBT], fecal immunochemical
test [FIT]).1 These tests vary with respect to their degree
of invasiveness, patient convenience, preparation requirements, amount
of colon evaluated, and test limitations (TABLE 1).
Common bowel-preparation techniques use polyethylene glycol
(PEG)–based osmotic laxatives to pull fluid into the gut and stimulate
repeated bowel movements that cleanse the site and allow improved
visualization during evaluation.6-9 Electrolytic salts of
potassium and sodium, along with the volume of water added to solubilize
the active ingredient and prevent water and electrolyte imbalances, are
additional components of these products. Newer products combine PEG
with a stimulant laxative or rely upon osmotic actions of sulfated salts
to trigger a cleansing diarrhea.9,10 (See TABLE 2 for
a comparison.) Methods of bowel preparation also may be classified
according to the amount of fluid (low or standard volume) the patient
Patients must precisely follow the directions for the specific
product to ensure an adequate result. The pharmacist can be a valuable
source of information when dispensing these prescription-only products
to the patient. These products can cause other effects in addition to
voluminous diarrhea; side effects such as nausea, vomiting, bloating,
abdominal distention, and electrolyte disturbances may occur, as well as
seizures, cardiac arrhythmias, and ischemic colitis (although rare).
Bowel-preparation kits generally are contraindicated in patients with GI
obstruction, bowel perforation, gastric retention, ileus, toxic
colitis, toxic megacolon, or known allergies to any of the active or
inactive components. Patients with impaired gag reflex are at risk for
aspiration, and these products should be used with caution under close
observation.6-10 The ACS guidelines and a discussion between
the patient and physician help determine which test should be employed,
and when. With some tests, such as FOBT, FIT, and CT of the colon (also
called virtual colonoscopy), a follow-up colonoscopy is required in the
event of a positive result in order to determine the reason for occult
blood in the stool or to further evaluate suspicious findings. Although
virtual colonoscopy continues to gain in popularity, concerns over the
degree of sensitivity, as well as the potential need for a follow-up
colonoscopy, lessen its value compared with traditional colonoscopy.4
ACS Screening Guidelines
The ACS guidelines for colorectal cancer screening are stratified according to a person’s risk for the disease (TABLE 3).
Patients deemed to be at increased risk for developing colorectal
cancer include those with a personal history of colorectal cancer or
adenomatous polyps, personal history of inflammatory bowel disease,
strong family history of colorectal cancer or polyps, or family history
of hereditary conditions associated with colorectal cancer (familial
adenomatous polyposis, hereditary nonpolyposis colon cancer).1
Individuals not meeting criteria for increased risk are considered to
be at average risk for developing colorectal cancer, and routine
screening is modified to reflect this reduced risk.11
Although only about 50% of people older than 50 years adhere to the ACS
guidelines, the benefits of colorectal screening cannot be ignored:
Patients diagnosed in the early stage of disease have a 5-year survival
rate of approximately 90%, while this value drops to 12% for patients
diagnosed with metastases reflective of advanced disease.1
If screening results in positive detection of a tumor, staging and
classification are performed to determine treatment and prognosis.
Classification involves the tumor-node-metastasis (TNM) method, in which
T1-T4 indicates the depth of tumor penetration into the bowel wall,
N0-N2 represents the involvement of regional lymph nodes, and M0-M1
denotes the absence or presence of distant metastases. Staging (I-IV) is
based upon how high the tumor scores in these three areas, with early
stages describing smaller tumors with more local involvement and later
stages denoting larger tumors that have spread deeper into the mucosa
and more broadly to regional lymph nodes and distant areas of the body
(i.e., liver, lungs, bone, and brain).3,12
Surgery, radiation, and systemic therapy are among the options
available to manage patients with colorectal cancer. Stage and
individual patient characteristics are the key determinants in treatment
selection. The extent and strategy of surgical resection depend upon
the tumor’s location and involvement with adjacent structures. Radiation
may be administered before or after surgery to improve resectability or
to reduce the probability of regional recurrence within the pelvic
area. Systemic therapy relies heavily on fluorouracil combined with
leucovorin, with a number of treatment regimens that vary by dose and
schedule. Additional systemic options include capecitabine, irinotecan,
oxaliplatin, and the monoclonal antibodies cetuximab, panitumumab, and
bevacizumab.3,13 Systemic therapy is typically administered
as adjuvant treatment following surgical resection in order to eliminate
any remaining micrometastases.13
Colorectal cancer is a common form of malignancy with identifiable
risk factors. Treatment can improve overall survival, especially when
the disease is diagnosed at an early stage. Screening methods are
available that facilitate early disease recognition. As highly
accessible health care practitioners, pharmacists represent a resource
for patients who have questions about screening recommendations or
require a catalyst to seek indicated care. The revised guidelines
developed by the ACS may be used by pharmacists, other health care
providers, and patients requiring information regarding colorectal
cancer screening. Pharmacists who are familiar with these guidelines can
assist patients in making informed decisions about screening for
colorectal cancer and can have a profound impact on their health.
1. American Cancer Society. Colorectal cancer early detection.
Accessed November 14, 2012.
2. American Cancer Society. Cancer Facts & Figures 2012. Atlanta, GA: American Cancer Society; 2012.
3. Mayer RJ. Gastrointestinal tract cancer. In: Longo DL, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw Hill Medical; 2012.
4. George TJ. Colorectal cancer. In: Abraham J, Gulley JL, Allegra CJ, eds. The Bethesda Handbook of Clinical Oncology. 3rd ed [online]. Philadelphia, PA: Lippincott Williams & Wilkins; 2010.
5. Moasser MM. Neoplasia. In: McPhee SJ, Hammer GD, eds. Pathophysiology of Disease: An Introduction to Clinical Medicine. 6th ed [online]. New York, NY: McGraw Hill Medical; 2010.
6. GoLytely (PEG-3350 and electrolytes) product information. Braintree, MA: Braintree Laboratories, Inc; November 2000.
7. NuLytely (PEG-3350, sodium chloride, sodium bicarbonate, potassium
chloride) product information. Braintree, MA: Braintree Laboratories,
Inc; February 2008.
8. MoviPrep (ascorbic acid, PEG-3350; potassium chloride, sodium
ascorbate, sodium chloride, sodium sulfate) product information.
Raleigh, NC: Salix Pharmaceuticals, Inc; April 2011.
9. HalfLytely (bisacodyl, PEG-3350, potassium chloride, sodium
bicarbonate, sodium chloride) product information. Braintree, MA:
Braintree Laboratories, Inc; July 2010.
10. SuPrep Bowel Prep Kit (sodium sulfate, potassium sulfate,
magnesium sulfate) product information. Braintree, MA: Braintree
Laboratories, Inc; August 2010.
11. National Comprehensive Cancer Network. NCCN Clinical Practice
Guidelines in Oncology. Colorectal cancer screening. Version 2.2012.
Accessed November 14, 2012.
12. Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010.
13. National Comprehensive Cancer Network. NCCN Clinical Practice
Guidelines in Oncology. Colon cancer. Version 3.2012.
www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed October
14. American Cancer Society. Colorectal cancer screening tests.
Accessed November 14, 2012.
15. American Cancer Society. Colorectal cancer early detection.
American Cancer Society recommendations for colorectal cancer early
Accessed November 14, 2012.
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