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!