1. General Medicine Subspecialty Conference Colon Cancer Screening General Medicine Subspecialty Conference Colon Cancer Screening Selim Krim, MD Assistant Professor Texas Tech University Health Sciences Center

2. U.S. Burden of Colorectal Cancer 153,760 new cases diagnosed in the United States in 2007 52,180 deaths in 2007 Second leading cause of cancer deaths in the United States About 6% of Americans are expected to develop the disease within their lifetime

3. Why is screening important? Why is screening important?

4. Adenoma to Carcinoma Pathway Regular screening for and removal of polyps can reduce a person's risk of developing colorectal cancer by up to 90 percent. Early detection of cancers that are already present in the colon increases the chances of successful treatment and decreases the chance of dying as a result of the cancer.

5. How and when should physicians start screening?

6. Colon Cancer Screening Screening programs should begin by classifying the individual patient’s level of risk based on personal, family, and medical history, which will determine the appropriate approach to screening in that person. Men and women at average risk should be offered screening for colorectal cancer and adenomatous polyps beginning at age 50 years.

7. Case 1 A 50-year-old man comes for an annual health maintenance visit. He feels well, and medical history is unremarkable. There is no family history of colorectal cancer. Physical examination and routine laboratory studies are normal. Which of the following is the most appropriate recommendation for colorectal cancer screening for this patient? A 50-year-old man comes for an annual health maintenance visit. He feels well, and medical history is unremarkable. There is no family history of colorectal cancer. Physical examination and routine laboratory studies are normal. Which of the following is the most appropriate recommendation for colorectal cancer screening for this patient? Fecal occult blood testing now; repeat every 2 to 3 years Flexible sigmoidoscopy now; repeat every 2 to 3 years Barium enema examination now; repeat every 2 to 3 years Colonoscopy now; repeat every 10 years Virtual colonoscopy (CT colonography) now; repeat every 10 years

8. ACS/USPSTF Recommendations Men and women at average risk should be offered screening with one of the following options beginning at age 50 years; Offer yearly screening with fecal occult blood test (FOBT) using a guaiac-based test with dietary restriction or an immunochemical test without dietary restriction. Offer flexible sigmoidoscopy every 5 years. Offer screening with FOBT every year combined with flexible sigmoidoscopy every 5 years. When both tests are performed, the FOBT should be done first. Offer colonoscopy every 10 years.

9. Case 2 A 50-year-old man comes for a general physical examination. He feels well and is asymptomatic. Medical history is significant only for hypertension treated with atenolol. He takes no other medications or over-the-counter drugs. Family history is unremarkable. Physical examination is normal. Results of routine laboratory studies are also normal, including a hemoglobin level of 14.8 g/dL (148 g/L). One of three stool sample submitted for fecal occult blood testing is positive. Which of the following is the most appropriate next step in evaluating this patient? A 50-year-old man comes for a general physical examination. He feels well and is asymptomatic. Medical history is significant only for hypertension treated with atenolol. He takes no other medications or over-the-counter drugs. Family history is unremarkable. Physical examination is normal. Results of routine laboratory studies are also normal, including a hemoglobin level of 14.8 g/dL (148 g/L). One of three stool sample submitted for fecal occult blood testing is positive. Which of the following is the most appropriate next step in evaluating this patient? Repeat fecal occult blood test Flexible sigmoidoscopy Repeat fecal occult blood test and flexible sigmoidoscopy Double-contrast barium enema examination Colonoscopy

10. ACS/USPSTF Recommendations If the result of a screening test is abnormal, physicians should recommend a complete structural examination of the colon and rectum by colonoscopy (or flexible sigmoidoscopy and double contrast barium enema if colonoscopy is not available). Offer yearly screening with fecal occult blood test (FOBT) using a guaiac-based test with dietary restriction or an immunochemical test without dietary restriction. Two samples from each of 3 consecutive stools should be examined without rehydration. Patients with a positive test on any specimen should be followed up with colonoscopy.

11. Case 3 A 32-year-old man comes for an annual health maintenance visit. His mother was diagnosed with colorectal cancer at 65 years of age. The patient reports no rectal bleeding or other symptoms. Medical history is noncontributory except for hypercholesterolemia. Physical examination is normal. When should this patient first undergo colorectal cancer screening? A 32-year-old man comes for an annual health maintenance visit. His mother was diagnosed with colorectal cancer at 65 years of age. The patient reports no rectal bleeding or other symptoms. Medical history is noncontributory except for hypercholesterolemia. Physical examination is normal. When should this patient first undergo colorectal cancer screening? Now, then every 5 years At age 40 years, then every 10 years At age 40 years, then every 5 years At age 45 years At age 50 years, then every 5 years

12. ACS/AGA Recommendations People with a first-degree relative with colon cancer or adenomatous polyp diagnosed at age >60 years or 2 second- degree relatives with colorectal cancer should be advised to be screened as average risk persons, but beginning at age 40 years. People with 1 second-degree relative (grandparent, aunt, or uncle) or third-degree relative (great-grandparent or cousin) with colorectal cancer should be advised to be screened as average risk persons.

13. Case 4 A 32-year-old man comes for an annual health maintenance visit. His mother was diagnosed with colorectal cancer at 55 years of age. The patient reports no rectal bleeding or other symptoms. Medical history is noncontributory except for hypercholesterolemia. Physical examination is normal. When should this patient first undergo colorectal cancer screening? A 32-year-old man comes for an annual health maintenance visit. His mother was diagnosed with colorectal cancer at 55 years of age. The patient reports no rectal bleeding or other symptoms. Medical history is noncontributory except for hypercholesterolemia. Physical examination is normal. When should this patient first undergo colorectal cancer screening? Now, then every 10 years At age 40 years, then every 5 years At age 40 years, then every 10 years At age 45 years, then every 5 years At age 50 years, then every 5 years

14. ACS/AGA Recommendations People with a first-degree relative (parent, sibling, or child) with colon cancer or adenomatous polyps diagnosed at age <60 years or 2 first-degree relatives diagnosed with colorectal cancer at any age should be advised to have screening colonoscopy starting at age 40 years or 10 years younger than the earliest diagnosis in their family, whichever comes first, and repeated every 5 years.

15. Case 5 A 65-year-old woman underwent initial colonoscopy 1 month ago for colorectal cancer screening. A 6-mm tubular adenoma of the sigmoid colon was found and removed during the examination. The patient has no family history of colorectal cancer. Which of the following is the most appropriate recommendation for colorectal cancer surveillance for this patient? A 65-year-old woman underwent initial colonoscopy 1 month ago for colorectal cancer screening. A 6-mm tubular adenoma of the sigmoid colon was found and removed during the examination. The patient has no family history of colorectal cancer. Which of the following is the most appropriate recommendation for colorectal cancer surveillance for this patient? Repeat colonoscopy in 1 year Repeat colonoscopy in 3 years Repeat colonoscopy in 5 years Flexible sigmoidoscopy in 5 years Virtual colonoscopy (CT colonography) in 5 years

16. ACS/AGA Recommendations Patients who have had 1 or more adenomatous polyps removed at colonoscopy should be managed according to the findings on that colonoscopy. Patients who have had numerous adenomas, a malignant adenoma (with invasive cancer), a large sessile adenoma, or an incomplete colonoscopy should have a short interval follow-up colonoscopy based on clinical judgment. Patients who have advanced or multiple adenomas (>3) should have their first follow- up colonoscopy in 3 years. Patients who have 1 or 2 small ( 3) should have their first follow- up colonoscopy in 3 years. Patients who have 1 or 2 small (<1 cm) tubular adenomas should have their first follow-up colonoscopy at 5 years.

17. Case 6 A 45-year-old woman is undergoing evaluation to determine the cause of iron deficiency anemia. The patient is otherwise healthy, and family history is unremarkable. Colonoscopy shows a 2-cm villous adenoma in the sigmoid colon; the adenoma is removed during the procedure. In addition to counseling regarding screening of family members, which of the following is most appropriate at this time? A 45-year-old woman is undergoing evaluation to determine the cause of iron deficiency anemia. The patient is otherwise healthy, and family history is unremarkable. Colonoscopy shows a 2-cm villous adenoma in the sigmoid colon; the adenoma is removed during the procedure. In addition to counseling regarding screening of family members, which of the following is most appropriate at this time? Repeat colonoscopy in 6 months Repeat colonoscopy in 3 years Repeat colonoscopy in 10 years Repeat colonoscopy in 5 years Annual fecal occult blood testing Referral for left hemicolectomy

18. ACS Recommendations Patients with 3-10 adenomas, any adenoma >1 cm, any adenoma with villous features, or high-grade dysplasia should have their next follow-up colonoscopy within 3 years.

19. Case 7 A 35-year-old man with a 10-year history of ulcerative colitis involving the entire colon comes for a follow-up office visit. A small bowel follow-through radiographic series obtained at the time of diagnosis was normal. The patient is doing well on mesalamine maintenance therapy. He has only occasional diarrhea and bleeding and has rarely required corticosteroids. A colonoscopic examination with biopsies 1 month ago showed changes of chronic ulcerative colitis but no signs of dysplasia. Which of the following surveillance options is most appropriate for this patient? A 35-year-old man with a 10-year history of ulcerative colitis involving the entire colon comes for a follow-up office visit. A small bowel follow-through radiographic series obtained at the time of diagnosis was normal. The patient is doing well on mesalamine maintenance therapy. He has only occasional diarrhea and bleeding and has rarely required corticosteroids. A colonoscopic examination with biopsies 1 month ago showed changes of chronic ulcerative colitis but no signs of dysplasia. Which of the following surveillance options is most appropriate for this patient? Repeat colonoscopy with biopsies starting at age 50; then repeat examination every 5 years Repeat colonoscopy with biopsies now; then repeat examination every 5 years Repeat colonoscopy with biopsies now; then repeat examination every 1 to 2 years Colonoscopy with biopsies only if the patient has symptoms refractory to medical therapy Barium enema examination or virtual colonoscopy (CT colonography) now; repeat studies every 1 to 2 years

20. ACS/USPSTF Recommendations In patients with inflammatory bowel disease ( UC or Crohn’s), cancer risk begins to be significant 8 years after the onset of pancolitis, or 12-15 years after the onset of left-sided colitis Colonoscopy with biopsies for dysplasia. Every 1-2 years. These patients are best referred to a center with experience in the surveillance and management of inflammatory bowel disease

21. Case 8 A 24 year old woman comes for a general physical examination. She feels well and is asymptomatic. Medical history is significant only for tonsillectomy at the age of 12. She takes no medications or over-the-counter drugs. 10 years ago, her father was diagnosed with familial adenomatous polyposis. Physical examination is normal. Results of routine laboratory studies are also normal. Which of the following is the most appropriate next step in managing this patient? A 24 year old woman comes for a general physical examination. She feels well and is asymptomatic. Medical history is significant only for tonsillectomy at the age of 12. She takes no medications or over-the-counter drugs. 10 years ago, her father was diagnosed with familial adenomatous polyposis. Physical examination is normal. Results of routine laboratory studies are also normal. Which of the following is the most appropriate next step in managing this patient? Colonoscopy every year starting at age 50 Colonoscopy every year starting at age 20-25 Colonoscopy every 2-3 years starting at age 20-25 Yearly stools for occult blood and flexible sigmoidoscopy (beginning at puberty) Refer for colectomy

22. ACS/USPSTF Recommendations People who have a genetic diagnosis of familial adenomatous polyposis (FAP), or are at risk of having FAP but genetic testing has not been performed or is not feasible, should have annual sigmoidoscopy, beginning at age 10-12 years, to determine if they are expressing the genetic abnormality. Genetic testing should be considered in patients with FAP who have relatives at risk. Genetic counseling should guide genetic testing and considerations of colectomy.

23. Case 9 32-year-old man comes for an annual health maintenance visit. Family history is positive for hereditary nonpolyposis colorectal cancer. The patient reports no rectal bleeding or other symptoms. Medical history is noncontributory except for hypercholesterolemia. Physical examination is normal. When should this patient first undergo colorectal cancer screening? Now At age 35 At age 40 years At age 45 years At age 50 years

24. ACS/USPSTF Recommendations People with a genetic or clinical diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) or who are at increased risk for HNPCC should have colonoscopy every 1-2 years beginning at age 20-25 years, or 10 years earlier than the youngest age of colon cancer diagnosis in the family--whichever comes first. Genetic testing for HNPCC should be offered to first- degree relatives of persons with a known inherited mismatch repair (MMR) gene mutation.

25. Case 10 Three months ago, a 62-year-old man underwent segmental sigmoid colon resection for a near-obstructing colorectal cancer found on flexible sigmoidoscopy. Surgery was considered curative, and the patient did not require postoperative chemotherapy or radiation therapy. He has no personal or family history of colorectal cancer or polyps. On a follow-up visit today, he feels well. Physical examination is normal. Which of the following is the most appropriate colorectal cancer surveillance procedure for this patient? Three months ago, a 62-year-old man underwent segmental sigmoid colon resection for a near-obstructing colorectal cancer found on flexible sigmoidoscopy. Surgery was considered curative, and the patient did not require postoperative chemotherapy or radiation therapy. He has no personal or family history of colorectal cancer or polyps. On a follow-up visit today, he feels well. Physical examination is normal. Which of the following is the most appropriate colorectal cancer surveillance procedure for this patient? Colonoscopy now Colonoscopy in 3 months Colonoscopy in 1 year Colonoscopy in 3 years CT scan of the abdomen now CT scan of the abdomen in 3 years

26. ACS/USPSTF Recommendations Patients with a colon cancer that has been resected with curative intent should have a colonoscopy around the time of initial diagnosis to rule out synchronous neoplasms. If the colon is obstructed preoperatively, colonoscopy can be performed approximately 6 months after surgery. If this or a complete preoperative examination is normal, subsequent colonoscopy should be offered after 3 years, and then, if normal, every 5 years.

27. Case 11 A 67-year-old man undergoes diagnostic colonoscopy after he has a positive fecal occult blood test. A sigmoid colon cancer is found. The remainder of the colonoscopic examination is normal, and a CT scan of the abdomen shows no findings suggestive of metastatic disease. The serum carcinoembryonic antigen (CEA) level is slightly elevated. The patient undergoes resection of the sigmoid colon with good results. Postoperative recommendations include follow-up office visits every 3 months for 3 years, CEA measurement, and surveillance colonoscopy. When should the first surveillance colonoscopy be performed? A 67-year-old man undergoes diagnostic colonoscopy after he has a positive fecal occult blood test. A sigmoid colon cancer is found. The remainder of the colonoscopic examination is normal, and a CT scan of the abdomen shows no findings suggestive of metastatic disease. The serum carcinoembryonic antigen (CEA) level is slightly elevated. The patient undergoes resection of the sigmoid colon with good results. Postoperative recommendations include follow-up office visits every 3 months for 3 years, CEA measurement, and surveillance colonoscopy. When should the first surveillance colonoscopy be performed? In 1 year In 3 years In 5 years Only if the CEA level increases

28. ACS/USPSTF Recommendations Patients with a colon cancer that has been resected with curative intent should have a colonoscopy around the time of initial diagnosis to rule out synchronous neoplasms. If the colon is obstructed preoperatively, colonoscopy can be performed approximately 6 months after surgery. If this or a complete preoperative examination is normal, subsequent colonoscopy should be offered after 3 years, and then, if normal, every 5 years.

29. Case 12 A 47-year-old woman is evaluated for abdominal discomfort of 3 months' duration accompanied by a change in stool caliber. Her medical history is otherwise noncontributory, and her family history is unremarkable. Physical examination, including rectal examination, is normal. Results of fecal occult blood testing are positive. Colonoscopy reveals a 3-cm sigmoid tumor confirmed as adenocarcinoma on biopsy. On resection of the mass, tumor invasion of the muscularis propria is identified, in addition to metastases in one regional lymph node. The postoperative recovery is uneventful, and the patient presents for a follow-up office visit. Which of the following is the most appropriate next step in management? A 47-year-old woman is evaluated for abdominal discomfort of 3 months' duration accompanied by a change in stool caliber. Her medical history is otherwise noncontributory, and her family history is unremarkable. Physical examination, including rectal examination, is normal. Results of fecal occult blood testing are positive. Colonoscopy reveals a 3-cm sigmoid tumor confirmed as adenocarcinoma on biopsy. On resection of the mass, tumor invasion of the muscularis propria is identified, in addition to metastases in one regional lymph node. The postoperative recovery is uneventful, and the patient presents for a follow-up office visit. Which of the following is the most appropriate next step in management? Adjuvant chemotherapy Radiation therapy Observation Immunohistochemical staining of tumor

30. Colon Cancer Classification Stage Stage Extent Extent Adjuvant chemotherapy indicated Adjuvant chemotherapy indicated 5 year survival Stage 0 Intramucosal Intramucosal No No 100% 100% Stage 1 Submucosa/Musc ularis mucosae No No 95% 95% Stage 2A Subserosa Subserosa No No 85% 85% Stage 2B Perforation Perforation No No 75% 75% Stage 3 Lymph nodes Lymph nodes (LN) (LN) Yes Yes 65% for up to 3+LN, 45% FOR>4LN Stage 4 Distant disease Yes Yes 5% 5%

31. Adjuvant chemotherapy after surgery Adjuvant systemic chemotherapy after resection of node positive colon cancer is associated with 30% reduction in the risk of disease recurrence, and 22 to 32% reduction in mortality. Remember for colon cancer only in stage 3 disease – adjuvant chemotherapy with oxaliplatin plus 5-FU and leucovorin. For rectal cancer: stage 2 and 3 disease : adjuvant chemotherapy + radiation

32. Questions ? Questions ?

33. Thank you Thank you