wwwmedscape.com Colorectal Cancer ). Screening Guidelines Update Pharmacist Michael Steinberg, PharmD, BCOP ). US Pharmacist. 2012;37(12):22-26. Abstract and Introduction Abstract In 2012, the American Cancer Society (ACS) revised its guidelines for colorectal cancer screening. The guidelines serve as a reference for recommendad tests and schedules based upon risk factors for developing colorectal cancer. Screening tests aro 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, Introduction Guidelines for cancer screening have been avallable 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.|"] This article will provide background information on the pathology and treatment of colorectal cancer and summarize the revised colorectal screening guidelines. Epidemiology 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. 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 60 years, history of hereditary intestinal polyposis and nonpolypasis conditions, personal or family history of colorectal cancer, history of inflammatory bowel disease (.., ulcerative cots or Crohn's disease), history of Streptococcus bovis bacteremia, use of ureterosigmoidostomy, and presence of type 2 diabetes." Lifestyle factors that may contribute to the development of colorectal cancer include a diet high in animal fat, tobacco use, physical inactivily, obesity, and heavy alcohol use." Night-shitt, work for 3 or more days per week for at least 15 years has been shown to have a weak link to colorectal cancer! Overall the lifetime risk of developing colorectal cancer is estimated to be 1 in 18.) Pathology Colorectal cancer arises in epithelial cels ofthe colon or ctum when multiple cumulative genetic mutations alter cl processes that normally restrict division, migration, and differentiation and confer malignant proliferative, invasive, and metastatic characteristics upon the cells. ®1 Once a tumar has gained malignant status, continued genetic instabity leads to further aterations that can affect the cancers properties overtime and impact sensitivity to treatment. Some ofthese mutations can serve as tumor markers for clinicians, such as activation of te latent gene encoding carcinoembryonic antigen, which can be measured in the blood to monitr treatment response or to detect recurrence 1 Most cases of colorectal cancer develop from polyps, growths that protrude from the mucosal surface into the gastrointestinal (GI) tract kamen.) Three types of polyps occur: hamartoma (unior polyp), hyperplastic mucosal proliferation (hyperplastic polyp), and adenomatous polyp. Adenometous isthe 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 eldery patients, which highlights the importance of proper screening to identity 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 tubulovilous, with villous adenomas the most likely to be cancerous. ‘Adenomatous polyps may be either sessile (lat) or pedunculated (stalked), with sessile types being more likely to progress to cancer. Finally, polyps greater than 2.5 om are five times more likely to be cancerous than those less than 1.5 cm (10% vs. 2%) Overal, ones an adenomatous polyp forms, it takes at least § years of growth to reach clinical significance, suggesting the need t. become cancerous. 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. itiate screening and perform routine follow-up evaluation to identify polyps that are of concern before they Symptoms 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.|" 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 fall to seek medical assistance However, the possibilly that these symptoms may represent a malignancy should be the impetus for an individual to seek a proper and prompt evaluation 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 identity cancer early in the course of disease, when cure is most Ikely."! 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}).{"! These tests vary with respect to their degree of invasiveness, patient convenience, preparation requirements, amount of colon evaluated, and test imitations (). Table 1. Screening Methods for Colorectal Cancer Method DescriptionNotes : Flexible, lighted, tubelike video camera inserted into rectum allows visualization of Jentire rectum, but less than half of colon Flexible sigmoidoscopy Requires bowel preparation Flexible, lighted, tubelike video camera inserted into rectum allows visualization of entire rectum and colon; has ability to remove any identified polyps Requires bowel preparation; use of sedation requires patient to rely on another person to drive hinvher home. after the procedure Colonoscopy Jcards and retums/mails completed kit to medical officellaboratory Double- Barium sulfate suspension is injected with contrast air into rectum via flexible tube; x-ay images | Retires bowel preparation; colonoscopy may be arium enema are taken performed to evaluatelremove any suspicious polyps. Patient lies within scanning machine, which | Requires bowel preparation; may require drinkable contrast ct rotates around him/her taking cross-sectional | solution, as well as insertion of ar into colon to improve colonography | images that enable 2-or 3-dimensional Visualization; colonoscopy may be performed to visualization of colon and rectum evaluatelremove any suspicious polyps Patient applies stool sample (usually 3 Requires colonoscopy for positive test to determine cause ost consecutive bowel movements) to test kit |of bleeding; NSAIDs, aspirin, vitamin C (250 mg/day), or red meat <3 days before testing interacts with accuracy; may not detect nonbleeding tumors Patient applies stool sample (usually 2-3FIT or FOBT iconsecutive bowel movements) to test kit Jcards and retums/mails completed kit to | of. medical officellaboratory Requires colonoscopy for positive test to determine cause bleeding; no dietary limitations; may not detect, nonbleeding tumors FIT: fecal immunochemical test; FOBT: fecal occult blood test; FOBT: immunofecal occult blood test; NSAID: nonsteroidal antiinflammatory drug. Source: Reference 14. ‘Common bowel-preparation techniques use polyethylene glycol (PEG)-based osmotic laxatives to pulll fluid into the gut and stimulate repeated bowel movements that cleanse the site and allow improved visualization during evaluation, 2) Electralytic 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 diantnea."0l (See for a comparison.) Methods of bowel preparation also may be classified according to the amount of fluid (low or standard volume) the patient must imbibe. Table 2. Bowel-Preparation Products Product contents [YO mixing PEG-3350, sodium sulfate, sodium Fill provided container Bicarbonate, ih loke- wom w2te" > | Rapidly dink (.e., do nt sip) 240 ml (8 oz.) prepared GoLYTELY 4 * solution every 10 min until watery stool is clear and chloride, ensure dissolution. May ene ton potassium be refrigerated, but use chloride, with ‘within 48 h for without pineapple flavoring PEG-3360, sodium berate, Fil poe catia chloride, ih loke- warm W2l2" > | Rapidly dink (Le, do not sip) 240 mL (8 oz.) prepared NULYTELY |potassium | 4L ensure dissolution, May |S0Uution every 10 min until watery stools clear and chloride, {ree of solid matter chon, lemon: be refrigerated, but use lime orange, within 48 h or pineapple lavoring PEG-3350, | (Split sodium dose Empty contents of 1 | (Spiit-dose regimen) Evening before exam: Drink 1st L sulfate, regimen) |Pouch A and 1 pouch B | solution over 1 h (one 8-02. glass every 15 min), then sodium Evening; | nto glass container (or | drink 500 mL. (16 oz.) clear liquid. Moming of exam chloride, 4.51; | container provided) and | Drink 2nd L solution over 1 h, then drink 500 mL. clear potassium | morning. | dd 1 L lukewarm water; | iquid 21 h before start of exam, (Evening-only regimen) MoviPrep |*hlotde, of exam: | mix to ensure ~6 pm evening before exam: Drink 1st L solution over 1 PN sodium 4.5L. |dissolution. May be | (one 8402. glass every 1 min); ~1.5h later, ink 2nd lascorbate, _| (Evening- |ffigerated, but use| solution over 1 h (one 8-02. glass every 15 min) Jascorbic acid, only | Within 24h. Do not add | pink additional L (32 oz.) clear liquid evening before additional flavorings to | exam solution[sata ain) ff Feerera889pring |3 [sodium chloride, sodium |Add flavor pack to bicarbonate, container, fill container potassium with water to 2 mark, | Day before evaluation: Wait up to 6 h for bowel chloride, 2b land shake until product | movement, then drink entire prepared solution at rate of cherry, lemon- ‘completely dissolved. |8 oz. every 10 min lime, orange, Do not add additional or pineapple flavorings to solution flavoring; bisacodyl § mg tablet HalfLytely and bisacody! tablet ‘Sodium sulfate, potassium sulfate, magnesium Pour contents of 1 bottle sulfate, 281 __ ||inte provided container sucralose, and fill with water up to sodium 16-02. line benzoate, malic acid citric acid, flavoring Evening before evaluation: Drink entire container of prepared solution, followed by 2 additional containers of ‘water (total 32 02. water) over next h. Moming of evaluation (~10-12 h later, but 21 h before evaluation): Drink entire container of 2nd prep-kit solution, followed by 2 additional containers of water (32 oz. total water) lover next h ‘Suprep Bowel Prep Kit min: minute; PEG: polyethylene glycol. Source: References 610. Patients must precisely follow the directions for the specifi 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, cardia arrhythmias, and ischemic colts (although rare). Bowel- preparation kits generally are contraindicated in patients with Gl obstruction, bowel perforation, gastric retention, ileus, toxic cali, toxic megacolon, or known allergies to any ofthe active or inactive components, Patients with impaired gag reflex are al risk for aspiration, and these products should be used with caution under close observation "91 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 orto futher evaluate suspicious findings, Although virtual colonoscopy continues to gain in popularity, concems over the degree of sensitvty, as well asthe potential need for a follow-up colonoscopy, lessen its value compared with traditional colonoscopy ACS Screening Guidelines ‘The ACS guidelines for colorectal cancer screening are stratified according to a person's risk for the disease (). 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 associate with colorectal cancer (familial adenomatous polyposis, herecitary 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"! Athough only about 50% of people older than 50 years adhere to the ACS guidolines, the benefits of colorectal screning cannot be ignored: Pationts diagnosed in the eaty stage of disease have a Syear survival rate of approximately 90%, while this value drops to 12% for patients diagnosed with metastases reflective of advanced disease." Table 3. ACS Guidelines on Colorectal Cancer Screening and Surveillance‘Average Risk + Flexible sigmoidoscopy every 5 y Colonoscopy every 10 y Double-contrast barium enema every 5 y CT colonography every 5 y FIT annually (take-home, multiple-sample method) ‘Starting at age 50 years, men and women should undergo one of the following screening tests: ‘+ FOBT annually (take-home, muttiple-sample method) Increased Risk (due to history of polyps on prior colonoscopy) Risk Category Age/Time to Begin Recommended Test t(s) [Colonoscopy or other Sm h i A ‘Small rectal hyperplastic polyps \ge 50 y sereening options 1-2 tubular adenomas with low-grade dysplasia <1 em |/5-10 y after polyp removal [Colonoscopy 3-10 adenomas or adenoma >1 cm or any adenomas By aft al Cot with high-grade dysplasia or villous features ¥ after polyp remo olonoscopy >10 adenomas found on single exam 53 y alter polyp removal [Colonoscopy ‘Sessile adenomas removed in pieces 2-6 mo after adenoma removal || Colonoscopy Increased Risk (due to history of colorectal cancer) Risk Category Colon or rectal cancer diagnosis 1@ to Begin [At time of colorectal surgery, or 3- 16 mo later if metastasis absent Recommended Test |Colonoscopy Colon or rectal cancer removed surgically <1 y after cancer resection or 1 y atter colonoscopy of remaining ‘colon [Colonoscopy repeated in 3 y; if normal, repeat every 5 y Increased Risk (due to FH of colorectal cancer) Risk Category [Age/Time to Begin Recommended Test (Colorectal cancer or adenomatous polyps in any 1st- degree relative <60 y or 22 ‘st-degree relatives at any age [Age 40 y, or 10 y before youngest immediate-family case [Colonoscopy every 5 y (Colorectal cancer or adenomatous polyps in any 1st- genetic testing degree relative 260 y or 22 2nd-degree relatives at any | Age 40 y [Colonoscopy every 10 y age High Risk Risk Category [Age to Begin Recommended Test(s) Yearly flexible FAP diagnosed by genetic testing, or suspected without | ao. 4q_ 4p y slgmokdoacopy; gonetlo testing [Age 20-25 y or 10y before [Colonoscopy every 1-2 y;HNPCC or FH of condition youngest immediate-family case | |genetic testing Unclear, but cancer risk begins <8 y after Colonoscopy with Inflammatory bowel disease biopsy pancolitis onset or 12-15 y after LC onset every 1-2 y ‘ACS: American Cancer Society; FAP: familial adenomatous polyposis; FH: family history; FIT: fecal immunochemical test; FOBT: fecal occult blood test; HNPCC: hereditary nonpolyposis colon cancer; LC: left-sided colitis. Source: Reference 15. ‘Adapted and used with permission from the American Cancer Society. Diagnosis 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, NO-N2 represents the involvement of regional lymph nodes, and MO-M1 denotes the absence ‘or presence of distant metastases. Staging (|-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 jgtgthe mucosa and mare broadly to regional lymph nodes and distant areas ofthe body (ever, lungs, bone, and brain) Treatment ‘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 ddopend upon the tumors locaton and involvement with adjacent structures, Radiation may be administered before or ater surgery to improve resectabilty or to reduce the probabilty of regional recurrence within the pelvic area. Systemic therapy roles heavily on fluorouracil combined with leucovorin, with a numberof treatment regimens that vary by dose and schedule. {Additional systemic options include capecitabine, inotecan, oxaliplatin, and the monoctonal antibodies cetuximab, panitumumab, and bevacizumab 19] Systemic therapy is typically administered as adjuvant treatment following surgical resection in order to eliminate any remaining micrometastases 13 Conclusion 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 seck 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, References 41, American Cancer Society, Colorectal cancer early detection, ‘www.cancer org/acs/groupsicid/documents/webcontent/003170-paf pat. 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, Ine; 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, Ine; August 2010, 11, National Comprehensive Cancer Network, NCCN Clinical Practice Guidelines in Oncology. Colorectal cancer screening, Version 2.2012. www.ncen.orgiprofessionals/physician_gls/pdficolorectal_screening.pdf. Accessed November 14, 2012. 12. Edge SB, Byrd DR, Compton CG, 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.ncon.org/professionals/physician_gls/pdticolon.paf, Accessed October 9, 2012, 14, American Cancer Society. Colorectal cancer screening tests. ‘www cancer org/cancericolonandrectumcancer/moreinformation/colonandrectumcancerearlydetection/colorectal-cancer- early-detection-screening-tests-used. Accessed November 14, 2012. 16. American Cancer Society. Colorectal cancer early detection. American Cancer Society recommendations for colorectal cancer early detection. ‘wwew.cancer.org/cancericolonandrectumcancerimoreinformation/colonandrectumcancerearlydetection/colorectal-cancer- earlysdetection-acs-recommendations. Accessed November 14, 2012. Us Pharmacist. 2012;37(12):22-26, © 2012 Jobson Publishing This website uses cookies to deliver its services as described in our Cookie Policy. By using this website, you agree to the use of cookies. close