2. Colon Cancer Matt Anderson, MD MSc Friday Teaching Seminar September 24, 2004

3. Learning Objectives Discuss current recommendations regarding colon cancer screening and their evidence base. Discuss the initial management and work-up of a patient with a biopsy showing colon cancer. Discuss treatment options and follow-up for both advanced and local disease.

4. So you want the answers? Colonoscopy liberally: Sx, anemia, over 50; (or over 40 if positive FH) If they have cancer refer to a surgeon and an oncologist. Do what they suggest you do?

5. Can we go home now, Anderson?

6. General 2002: 148,000 new cases –107,000 colonic, 41,000 rectal. –57,000 death Mainly (90%) adenocarcinomas. 90% in people over 50 years

7. Risk factors for colon ca 75 to 80% of colon cancer is in people with no risk factors (“sporadic”) Intermediate risk: personal history of colorectal polyps or FH of first degree relative w/ colon cancer or adenomatous polyps. High-risk: Familial hereditary cancer syndromes (e.g. Familial adenomatous polyposis, Heredity nonpolyposis colorectal cancer) or inflammatory bowel disease.

8. How do you “prevent” colon ca?

9. Prevention Fecal Occult Blood testing Aspirin NSAID’s reduce adenomas in patients w/ high risk familial syndromes Calcium: 1200 mg/d prevents recurrent adenomas in patients w/ adenoma hx (RCT) No evidence for benefit from high-fiber diets.

10. People w/ symptoms All patients (except menstruating women) with iron-deficiency anemia are candidates for colonoscopy. Look for a microcytic anemia and a low Ferritin. Symptoms of colon cancer include: –new abdominal pain/abdominal symptoms –change in bowel habits, –blood in the stool –Weight loss –Anemia sx: fatigue

11. What are the screening modalities?

12. Screening Modalities Guaic-cards Sigmoidoscopy Colonoscopy Double-contrast barium enema Virtual colonoscopy using CT/MRI DNA stool tests

13. FOBT 3 consecutive stool samples. Rehydration increases sensitivity, decreases specificity. Pts should follow special diet. 1993 Minnesota RCT showed that “about a 1000 people would need to be screened annually over 10 years to prevent one death from colorectal cancer.” 38% will end up getting colonoscoped over 13 yrs. Am Fam Physician 2002;66:297-302 No evidence for benefit from a sample collected during PE.

14. Double contrast BE Winawer et. al. compared DCBE w/ colonoscopy in patients w/ a history of adenoma. Compared to colonoscopy, DCBE has a sensitivity of: –32% for adenomas less than ½ cm –53% for adenomas between 0.6 and 1 cm –48% for adenomas over 1 cm. Specificity was 85% (i.e. 15% false pos) N Engl J Med 2000:342:1766-72.

15. Sigmoidoscopy Images about ½ of the colon & requires no anesthesia. Obviously less sensitive than colonoscopy, but perforation rate is 1/10,000 as compared with 2/1000 with the colonoscope. Typically polyps are not biopsied so that about ¼ of pts will need a colonoscopy.

16. Evidence Basis FOBT: 3 large RCT’s DCBE: not even controlled trials Flex sig: controlled studies Colonoscopy: “indirect evidence” from the FOBT & flex sig trials. JAMA 2003:289:1288-1296

17. Surgery Resect tumor, mesentery and regional mesentery (best 12 lymph nodes). Thoroughly explore abdomen for metastatic disease. There does not seem to be good evidence concerning primary vs secondary closure of the colon.

18. StageDescription% Patients % 5-yr survival IInvades the submucosa or muscularis, no LN 1590 plus IIInvasion beyond muscularis, no regional LN involvement 20-3070% IIIRegional lymph node involvement 30-4050% * IVDistant metastasis20-25%Few cured *improves to 60-65% w/ chemotherapy.

19. Chemotherapy No demonstrated benefit for patients w/ stage I or II disease. Stage III: 5-FU and leucovorin; typically 5 days every 4 weeks for six cycles. Radiotherapy is used for rectal cancers.

20. Metastatic disease Resection of up to 3 liver lesions improves survival. Mainstay of therapy is usually chemotherapy: 5-FU +/- leucovorin. Newer drugs include irinotetin.

21. Chemotherapeutic agents: older 5-FU: –Pyrimidine antagonist; interferes w/ thymidlyate synthesis –Mucositis, alopecia, myelosuppression, diarrhea/vomiting. Irinotecan (Camptosar): –Inhibits topoisomerase I which is needed for DNA synthesis. –Diarrhea, often serious, is major side effect.

22. Newer agents Oxaliplatin (Eloxatin): –inhibits DNA sythesis by causing cross- linkages. –Significant neurotoxicity. –May show promise for both initial and rescue therapy.

23. Newer agents Cetuximab (Erbitux): –Monoclonal Antibody to EGFR (epithelial growth factor receptor) –Most common side effect: acne-like rash Bevacizumab (Avastin) –Monoclonal ab to Vascular endothelial growth factor –2% risk of GI bleed. –Can prolong survival

24. Recurrence Usually within 3 to 5 years of surgery. Typically in liver, site of original tumor, abdomen & lung. Evidence on surveillance strategies not great. Meta-analysis found that “intensive surveillance strategies” reduced RR of death by 20% (absolute risk reduction 7%). –NEJM 2004:350:2375-82

25. Surveillance strategies History/PE/routine lab tests: Risk of recurrence greatest in those w/FH & those diagnosed at age 50 or younger. Chest X-ray CEA CT abdomen (or) US of the liver Colonoscopy currently preferred method

26. How often colonoscopy? ESMO: Colonoscopy q5 yrs. NCCN: 1 yr after primary (6 mo if obstructing); q1yr if abnormal, q3yr if neg. ASCO: Colonoscopy q 3-5 yrs. Figueroa: Yearly if polyps or high risk, q 3- 5 yrs if normal. Berman: q 3-5 yrs. –NEJM 2004:350:2375-82

27. Have a nice weekend!