Colon cancer

1. COLORECTAL
CANCER
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2. LearningObjectives
By the end of the session, you should
be able to:
1. Epidemiology
2. Risk factors
3. Screening & prevention
4. Stages of the disease
5. Sign and symptoms
6. Treatment protocols
7. Side effects/complications
8. Prognosis
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3. Definition
 Malignant growth of tumor that begins from the inner
wall of the colon or rectum.
 Can also involve the anal canal.
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4. EPIDEMIOLOGY
 The 3rd most common malignancy worldwide ( ≥ 1.2
million new cases annually).
 The incidence is greatest among males (37.4 per
100,000 vs. 29.9 per 100,000)
 3rd leading cause of cancer-related deaths in US.
 Highest incidence rates in economically developed
countries
 Invasive CA of rectum occurs less frequently (<1/3
cases)
 In Palestine: (W.B)
 The 2nd most common cancer being diagnoses
 Cancer 2nd leading cause of death (M +F )
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5. Age & Colorectal CA
Relationship:
 An individual’s risk of developing cancer of the
colon or rectum increases with advancing age.
 The likelihood of cancer diagnosis ↑ after 40
years of age and rising progressively after age 50.
 The median age at diagnosis is 69 years.
 < 20% of patients are less than 50 years of age at
the time of diagnosis.
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6. SURVIVAL :
 5-year survival rate:
Disease Stage 5- Year
survival
Early stages (localized/stage I, II) of colon 91 %
Early stages rectal cancer. 88%
Regional disease/Stage III:
Colon & rectal cancer after the tumor has spread
regionally to adjacent LNs or tissues
70%
Metastatic disease ≤ 12%
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7. Pathophysiology
 The formation of colorectal CA is a multistep process.
 Begins with an abnormal growth of tissue known as a
polyp (precursors to the disease) originating from the
innermost wall of the colon.
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8.  The process of
transformation from polyp
to malignant disease
takes years.
 Once transformation
occurs, cancer begins to
spread through the wall
of colon/rectum.
 It can eventually invade
blood, L.Ns, or other
organs directly.
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A stalked colon
polyp

9.  95% are adenocarcinoma (glandular tissue).
 The disease can be prevented by removal of precancerous
tissue.
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10. Aetiology
 Aetiology is complex, involving:
 Patient- specific factors
 Environmental factor
 Genetic factors
 Genetic mutations associated with colorectal cancer:
 APC mutation/loss (Tumour suppressor gene).
 P53 mutation
 COX-2 overexpression (growth factor signalling
pathways)
 K-RAS mutation 35%, BRAF mutation 5% (oncogenes)
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11. Risk Factors
 Increase age: Age >50 (90% of patients)
 Male sex
 Family history.
 Personal history:
(history of colon polyps; multiple adenomas or size
≥10 mm)
 IBD (Ulcerative colitis, Crohn’s disease):
 ↑ 5- to 10-fold
 Risk ↑ with increasing extent of bowel involvement &
disease duration.
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12. Risk Factors
 Environmental factors/ Lifestyle:
 Physical inactivity & obesity
 Diet:
 fatty food
 Red meats
 processed meats
(hot dogs and some luncheon meats)
 low fibers
 Alcohol (excessive)
 SMOKING:
 Rectal > colon
 Dose relationship (pack/year)
 Duration
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13.  Particularly smoking in early life.
 As compared to never-smokers, the risks of
colorectal cancer and mortality in smokers were
18% and 25% higher, respectively.
 Early tobacco use  influence risk of cancer
recurrence and mortality among colon cancer
survivors.
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14. Risk Factors
 Genetic/Hereditary colon CA Syndromes:
 The 2 most common forms of hereditary colon
cancer are:
1. Familial adenomatous polyposis (FAP):
 Risk ↑ 100%
 AD
 Mutations of the adenomatous polyposis coli (APC)
gene
 0.2% to 1% of all colorectal cancers.
 Diagnosed by late teens or early 20s.
 Total colostomy is recommended when detected.
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15. 2. Hereditary non-polyposis colon cancer (HNPCC)/
Lynch Syndrome.
 AD
 2% to 4%
 MMR (mismatch repair) genes mutation in DNA.
 Diagnosed later in life as compared to FAP
 Tend to be located primarily in the right-sided (proximal
colon)
 Other factor can increase risk of colon cancer:
 DM (Type 2)
 in 15 studies (hyperinsulinemia & ↑ levels of free insulin-
like growth factor-1 (IGF-1), promote tumor cell
proliferation
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16.  Factors may ↓ colorectal CA risk:
 Fiber (Fruit & Vegetables)
 Physical activity
 Regular consumption of milk/Calcium & Vitamin D
(May have antiproliferative effects )
 Hormone replacement therapy (HRT). Persist over
10 y
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17.  NSAID (Celecoxib) and Aspirin Use:
 Regular use (2 x wk), over 10-15 year.
 Inhibition of COX-2 & free radical formation.
 COX-2 overexpression is seen in pre-cancerous &
cancerous lesions in the colon
 COX-2 overexpression is associated with:
 Decreased colon CA cell apoptosis
 Increased production of angiogenesis-promoting
factors.
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18. Signs & Symptoms
1. Subtle & nonspecific (generalised symptoms)
2. Asymptomatic (early stage).
3. **Persistent/sudden change in bowel habits:
(*Prolong constipation
*or diarrhea.
*pencil thin stool)
4. Bleeding from rectum or blood
In stool.
5. Vague Cramping or abdominal pain/discomfort,
bloating , N, V  2ndry obstruction, perforation,
bleeding.
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19. Signs and symptoms
6. Weakness and tiredness
(advanced stage).
7. Iron-deficiency anemia.
8. Unintentional weight loss
9. Increased liver enzymes
(sign of liver metastasis) (AST/ALT)
10. Hepatomegaly and jaundice
in advanced disease.
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20. Symptoms 20

21. Anatomy
 The large intestine consists of the cecum; the ascending,
transverse, descending, and sigmoid colon; and the rectum
 Ascending colon (22% of colorectal carcinomas)
 Transverse colon (11% of colorectal carcinomas)
 Descending colon (6% of colorectal carcinomas)
 Sigmoid colon (55% of colorectal carcinomas)
 4 major tissue layers, from the lumen outward, form the large
intestine:
 The mucosa
 Submucosa
 Muscularis propria
 Serosa
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22. 22

23. 23

24. DIAGNOSIS
 Signs and symptoms
 Entire Large bowel evaluation:
 Colonoscopy
 Double-Contrast Barium Enema
 CT Colonography (detect adenomas at least 6 mm).
 Flexible sigmoidoscopy (FSIG) : examine lower half of
the bowel to the splenic flexure, capable to detect
50%-60% of CA.
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25. DIAGNOSIS 25

26.  Biopsy
(during colonoscopy)
 Ultrasound: Determines
depth of tumor penetration,
assessing L.Ns
 CT scan: same as ultrasound + useful in assessing for
metastasis
 Blood tests: bld count, PT, PTT, Liver function test.
 CEA (carcinoembryonic antigen)Tumour marker
 Non-sensitive, non specific in early stage
 Usually elevated in metastatic or recurrent colon CA
 Normal 0-3 ng/mL
 Monitor the recurrence.
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27. SCREENING
 Often same as diagnosis
 Colonoscopy: gold standard for colorectal
screening
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28. SCREENING
A. Colonoscopy/ Barium enema/ CT scan
(alternative for individuals who don’t wish to
undergo /not suitable for colonoscopy.)
B. CEA level
C. Fecal screening test:
1. Fecal occult blood testing (FOBT)
 Many early-stage tumors do not bleed.
 High false -ve rate
 Sensitivity 33-75%
 Increased sensitivity & specificity when used in
combination with test 2
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29. 2. Fecal immunochemical test (FIT)
 Can be used to replace FOBT
 Sensitivity 60-85%
 Specificity > 97%
 No drug or food interactions
 Uses ABs to detect globin protein Hg in stool
D. Digital Rectal Exam (DRE):
Can detect anorectal
palpable mass
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30.  Screening guidelines for early detection of colorectal
CA with the goal of cancer prevention:
Risk Screening recommendation
Average risk
(R.F ≥ 50 ys)
both M/F
 Annual DRE and FOBT/FIT and one of the following:
– Sigmoidoscopy every 5 years
– CT colonography every 5 years
– Colonoscopy every 10 years
– Barium enema every 5 years
Family History Begin screening at age of 35-40 years or 10 years younger from
first-degree relative colorectal cancer diagnosis
IBD Begin screening at 8–15 years after diagnosis
FAP Begin screening at 10-12 years
HNPCC Begin screening at age of 20–25 years or 10 years younger
from 1st-degree relative colorectal CA diagnosis
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31. Staging:
TNM Staging System
 T – (tumor size), based on DEPTH (penetration)  invasion
into mucosa
 T1 – Tumour invades the submucosa
 T2 – Invades the muscularis propria
 T3 – Invade through the muscularis propria into
subserosa
 T4 – Tumors invading or adhering other local
organs/structures/segments/ surface of visceral
peritoneum
 N – lymph node involvement
 N1 – 1-3 +ve L.N
 N2 – ≥ 4 or more +ve L.N
 M – distant metastasis
 M0 – no other organs involved
 M1 – distant metastases are present
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32. 32

33.  Simplified Staging System
Stage
Stage I Tumors that either invade into or through the
submucosa with NO (+) LN
Stage II Tumors that invade through the muscularis propria or
into local organs with NO (+) LN
Stage III Any T with nodal involvement (+) LN
Stage IV  Tumor with nodal involvement and with distant
metastasis (usually liver, followed by lungs, then
bones)
 25% of patients present with stage IV
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34. 34

35. Treatment
I. Surgery
II. Radiation
III. chemotherapy
IV. Targeted molecular therapies.
 Treat Depend on the location & extent of disease.
 Prognosis depend on extent of tumour
penetration/LNs involvement, Metastases.
 Goals:
 Curative therapy for localized CA
 Palliative therapy for metastatic CA.
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36. Treatment
 Surgery in CA of the colon or rectum (stage, I, II, III):
 Complete surgical resection of the primary tumor
mass with regional lymphadenectomy
 At least a 5 cm margin of tumor-free bowel &
regional lymphadenectomy
 Selected patients with resectable metastases,
surgical resection may be an option.
 Rectal CA  total excision of the mesorectum
(TME), the surrounding tissue containing perirectal
fat and draining LNs.
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37. Treatment
 If the distal margin clear of tumor is at least 1 cm,
sphincter-preserving surgery may be possible for
patients with CAs in the middle and lower portion of
the rectum.
 If not Candidate for sphincter-preserving surgery 
Abdomino-perineal resection (APR) = remove distal
sigmoid, recto-segmoid, rectum, anus.
 Colostomy (after colectomy) has become an
accepted procedure for colon and rectal cancer.
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39.  Rectal CA is more difficult to resect with wide margins.
 Local recurrence of rectal CA is more common
compared to colon CA
 If lies closer to the anal sphincter, so the risk of
localized treatment failure & recurrence at the initial
site of disease is increased
 Radiation (XRT) is usually reserved for rectal cancer
 Adjuvant XRT + chemo. are standard for stage II/III
rectal CA
 Neo- Adjuvant therapy before rectal surgery to:
Shrink the tumour & make it resectable, prevent local
recurrence in rectal CA.
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40.  In metastasis disease, radiotherapy will reduce the
symptoms
 Stage I colon or rectal cancer are cured by surgical
resection alone, adjuvant therapy is not indicated.
 Adjuvant chemotherapy in –ve L.N (stage II) colon
cancer is controversial
 Adjuvant chemotherapy should be considered for
stage II disease with pts. at higher risk for relapse :
(inadequate LN sampling, bowel obstruction/ perforation of the
bowel at presentation, poorly differentiated tumors, perineural
invasion, and T4 lesions (stage IIB/IIC).
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41.  Adjuvant chemotherapy is standard therapy
for patients with stage III colon cancer
(decreases risk of cancer recurrence & death)
 Combined neo-adjuvant therapy + radiation
therapy (chemoradiation) and surgery for
patients with stage II or III rectal cancer is
considered standard of care to decrease risk
of local and distant disease recurrence.
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42. Stage Management
Stage I Surgery
Stage II Colon: Surgery (observation +/- chemo.)
Rectal: Surgery + XRT + chemo.
Stage III Colon: Surgery + Chemotherapy
Rectal: Surgery + XRT + chemo.
Stage IV +/- surgery (selected pt.)+ chemo. + MoAB ,
Palliative care
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