Colon Cancer
Matt Anderson, MD MSc
Friday Teaching Seminar
September 24, 2004
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.
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?
Can we go home now, Anderson?
General
• 2002: 148,000 new cases– 107,000 colonic, 41,000 rectal.– 57,000 death
• Mainly (90%) adenocarcinomas.
• 90% in people over 50 years
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.
How do you “prevent” colon ca?
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.
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
What are the screening modalities?
Screening Modalities
• Guaic-cards
• Sigmoidoscopy
• Colonoscopy
• Double-contrast barium enema
• Virtual colonoscopy using CT/MRI
• DNA stool tests
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.
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.
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.
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
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.
Stage Description %
Patients
% 5-yr
survival
I Invades the submucosa or muscularis, no LN
15 90 plus
II Invasion beyond muscularis, no regional LN involvement
20-30 70%
III Regional lymph node involvement
30-40 50% *
IV Distant metastasis 20-25% Few cured
*improves to 60-65% w/ chemotherapy.
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.
Metastatic disease
• Resection of up to 3 liver lesions improves survival.
• Mainstay of therapy is usually chemotherapy: 5-FU +/- leucovorin.
• Newer drugs include irinotetin.
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.
Newer agents
• Oxaliplatin (Eloxatin): – inhibits DNA sythesis by causing cross-
linkages. – Significant neurotoxicity. – May show promise for both initial and rescue
therapy.
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
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
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
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
Have a nice weekend!