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COLORECTAL CANCER
Ozlem Uysal-Sonmez, MD
Yeditepe University Hospital
Department of Medical Oncology
Anatomy of the Colon and
Rectum
• The colon + rectum = the large intestine
• Colon makes upto first 150-180 cm of
large intestine
• Rectum makes up the last 12-15cm
ending at the anus
The Colorectum
Epidemiology
• Third most common cancer
• Second most common cause of
cancer death
• Male = Female
• Lifetime probability of 6% (1 in 17)
• Very curable if detected in early stages
Epidemiology
• Males=Females
• Risk increases with age
– Average age at diagnosis is 67-70 yrs
• Highest in industrialized nations:
– Canada, US, N/W Europe
• Most cancers start as polyps precancerous growths that develop on the
inner wall of the colon and rectum
Most of the colon and Rectum
cancers are diagnosed at:
1) Routine physical to evaluate anemia
2) Screening colonoscopy
recommended for age 50 and over
How Does Colorectal Cancer Develop?
10 years
Janne PA, Mayer RJ. N Engl J Med 2000;342:1960.
Etiology
• Polyps (adenomatous)
• Diet
• High-calorie, high-fat Western diet
• Inflammatory bowel disease
• Ulcerative collitis
– Risk varies directly with extent of colonic involvement
and duration of active disease
– Cumulative risk: 2% at 10 years, 8% at 20 years, 18% at
30 years
– Screening: Annual or semiannual colonoscopy in disease
>8 years duration
• Crohn’s disease
– Risk increased 1.5-2 folds
Etiology
• Genetic factors
– Family history: depends on age of onset and number
of relatives
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One 1st degree relative with CRC - 2 to 3 x risk
Two 1st degree relative with CRC -3 to 4 x risk
1st degree relative < 50 years - 4 to 6 x risk
One 2nd degree relative with CRC- 1.5 x risk
One 1st degree relative with polyp - 2 x risk
– Hereditary syndromes (gene changes)
• Familial adenomatosis poli
• HNPCC (Hereditary nonpoliposis colorectal cancer)
Etiology
• Smoking
• Other factors
• Personal or family history of other cancers (breast,
endometrium, ovary)
• Exposure to asbestos (risk 1-2x)
Risk factors for Colorectal Cancer
Family
History
15-20%
HNPCC
5%
FAP-1%
IBD-1%
Sporadic/
Average Risk
75%
Risk groups for screening
• Average risk
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Age ≥ 50 y
No inflammatoy bowel disease
No history of adenoma or colorectal cancer
Negative family history
• Increased risk
– Personal history of
• Adenoma/sessile serrated polyp
• Inflammatoy bowel disease
• Colorectal cancer
– Positive family history
• High risk syndromes
– Lynch syndrome/Hereditary nonpolyposis colorectal cancer (HNPCC)
– Polyposis syndromes (familial adenomatous polyposis, PeutzJeggers syndrome, Juvenile polyposis syndrome, hyperplastic
polyposis syndrome)
Screening tests for colorectal cancer
Average risk
Starts at age 50
1. Colonoscopy every 10 years
•
•
preferred if available
For every 1% increase in complete colonoscopy rate, the hazard of
death decreased by 3%.
2. Annual FOBT+Flexible sigmoidoscopy every 5 years
Annual Fecal occult blood test (FOBT)
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•
Testing of stool for occult blood to detect colorectal cancer at an early
stage
Variation is observed in estimates of the sensitivity but its lower cost and
increased specificity to detect right-isded colonic lesions make it a good
screening test
Flexible sigmoidoscopy every 5 years
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•
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In contrast to FOBT, has a high sensitivity and specificity
Involves the use of a 60 cm flexible sigmoidoscope
Detects left sided lesions
Screening
• Average risk
– Colonoscopy every 10 yrs
– Annual fecal occult blood test (FOBT) + Flex
sigmoidoscopy every 5 years
– Double contrast barium every 5-10 yrs
• High-Risk
– Depends on risk
Who is High Risk?
• Familial Polyposis (APC Mutation)
– Sigmoidoscopy in teenage years
– Colectomy
• HNPCC (Mismatch Repair Genes)
– Colonoscopy in 20’s
• Family History:
– Colonoscopy 10 years younger than
index family case
Screening Strategies
One-Stage Screening
Colonoscopy
Two-Stage Screening
• FOBT+ Flex Sig.
• Virtual
Colonoscopy
Colonoscopy
Prevention
• Periodic sigmoidoscopy+FOB or
colonoscopy
• Diet
• NSAID: Sulindac, aspirin
Pathology and natural history
• Pathology
– Adenocarcinoma is most common type
– Cancers of anal verge: Most often squamous cell or basaloid
carcinomas
• Most arise from adenomatous polyps
Site Distribution
Pathology and natural history
• Proximal tumors
– More genetically unstable
– May arise through same mechanisms
underlying HNPCC
• Distal tumors
– greater genetic stability
– May develop through same mechanisms
underlying polyposis-associated colorectal
cancer
Natural history
• Tumors spread through the walls of the intestine and into
the lymphatic system
• Metastases to lymph nodes in 40%-70%
• Tumors most commonly spread to the liver because
venous blood flow from the colorectal tumor is through
the portal vein
• Most common: Liver, peritoneal cavity, lung
• Rectum cancers are 3 times more likely to recur locally,
because most of rectum lacks serosal layer
• Because of venous and lymphatic drainage of rectum to
inferior vena cava, rectum cancers often recur first in lung
Clinical Manifestations
• Many colorectal cancers cause no symptoms in the early
stages.
• Goal of screening is to detect cancers in the early
stages, before symptoms develop.
• Symptoms in the later stages include:
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Change in bowel habits
Blood in stool
Fatigue
Loss of appetite
Abdominal pain
Nausea
Weight loss
Anemia.
Clinical Manifestations
• Cancer on the right side gives rise to
manifestations that are different from those on
the left side of the colon
• Left-sided lesions
• Rectal bleeding
• Alternating constipation and diarrhea
• Narrow, ribbonlike stools
• Right-sided lesions
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•
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Usually asymptomatic
Vague abdominal discomfort
Iron deficiency anemia
Occult bleeding
Diagnosis & Staging
• General evaluation
– History, Physical examination with digital rectal
examination
– CBC, liver function tests
– Chest x-ray
• Carcinoembryonic antigen (CEA) screening
• Colonoscopy or sigmoidoscopy or barium enema
• Imaging tests
– CT scan or MRI
– Ultrasound, Endorectal ultrasonography
Colon Polyp
Colon Cancer
Staging
• Stage I- Invades into muscle layer, but not into
subserosa
• Stage II- Invades into subserosa, other organs,
or associated with perforation, no nodal
involvement
• Stage III- Lymph Node involvement
• Stage IV- Distant spread to other organs (liver,
lungs)
Layers of the Colon Wall
Prognostic factors
• Stage
• Histological grade
• Clinical presentation
• Perforation, obstruction worse
• High serum CEA level prior to surgery
Prognosis
• Stage is the most powerful predictor of prognosis.
• Five-year relative survival by stage
Stage I
>90%
Stage IIA
Stage IIB
70-85%
55-65%
Stage IIIA
Stage IIIB
Stage IIIC
45-55%
35-45%
25-35%
Stage IV
8%
Treatment
• Treatment of colorectal cancer is one of the most rapidly changing
and advancing areas in cancer research.
• Surgery is the mainstay of therapy
• Adjuvant chemotherapy
– Large cancers or cancer that has spread to lymph nodes may
have left behind few scattered cancer cells in the body, even
though no remaining cancer is detectable.
– Chemotherapy, 5-FU-based, may be recommended.
– Stage III patients benefit most from chemotherapy after surgery.
– Some Stage II patients may also benefit.
– Usually given for 6 months.
• Radiation:
– Has a major role in rectal cancer
– Given either before surgery, or after surgery
Treatment
• Stage I-III: Goal is cure
– Surgery
– Adjuvant chemotehrapy: Stage III, some stage II
• 5-Fluorouracil based
• Oxaliplatin
– Adjuvant radiotherapy: Rectal cancers
Treatment
• Stage IV:
– Goals of therapy: palliation
• To improve cancer-related symptoms
• To control cancers by delaying further growth and
spread
• To shrink cancers
• To improve survival (ie. to live longer with cancer)
– Chemotherapy: not curative
– Palliative surgery and radiotherapy
Chemotherapy
• 5-Fluorouracil based
• Chemotherapeutics: Irinotecan, oxaliplatin
• Targetted agents
– Anti VEGF antibody: Bevacizumab
– Anti-EGFR antibody: Cetuximab
Summary
• Early detection is crucial
• The development of new drugs and new
drug combinations will continue to improve
the outcome for cancer patients.