Colorectal Cancer

What is Colorectal Cancer?

Third most common type of cancer and second
most frequent cause of cancer-related death
A disease in which normal cells in the lining of the
colon or rectum begin to change, grow without
control, and no longer die

Usually begins as a noncancerous polyp that can,

over time, become a cancerous tumor

United Kingdom (2008)

Colorectal Cancer

Each year around 289,000 people are newly diagnosed with

cancer and breast, lung, colorectal and prostate cancer
account for over half of all the new cases (ONS, 2008a; ISD online,
2008a, WCISU, 2008; Northern Ireland Cancer Registry, 2008)

Epidemiology
peak incidence: 60 to 70 years of age
< 20% cases before age of 50
adenomas presumed precursor lesions for
most tumors
males affected 20% more often than females

Epidemiology
worldwide distribution
highest incidence rates in United States,
Canada, Australia, New Zealand, Denmark,
Sweden, and other developed countries

Etiology
genetic influences:
preexisting ulcerative colitis or polyposis
syndrome
hereditary nonpolyposis colorectal cancer
syndrome (HNPCC, Lynch syndrome) germ-line
mutations of DNA mismatch repair genes

Etiology
environmental influences:
dietary practices

low content of unabsorbable vegetable fiber

corresponding high content of refined carbohydrates
high fat content
decreased intake of protective micronutrients (vitamins
A, C, and E)

use of Aspirin and other NSAIDs: protective effect

against colon cancer?
cyclooxygenase-2 & prostaglandin E2

Carcinogenesis
chromosome instability pathway

Carcinogenesis
mismatch repair (microsatellite instability) pathway

What Are the Risk Factors

for Colorectal Cancer?
Polyps (a noncancerous or precancerous growth
associated with aging)
Age
Inflammatory bowel disease (IBD)
Diet high in saturated fats, such as red meat
Personal or family history of cancer
Obesity
Smoking
Other

Hereditary Colorectal Cancer

Syndromes: HNPCC
Hereditary non-polyposis colorectal cancer (HNPCC),
sometimes called Lynch syndrome, accounts for
approximately 5% to 10% of all colorectal cancer cases
The risk of colorectal cancer in families with HNPCC is
70% to 90%, which is several times the risk of the
general population
People with HNPCC are diagnosed with colorectal
cancer at an average age of 45
Genetic testing for the most common HNPCC genes is
available; measures can be taken to prevent
development of colorectal cancer

Hereditary Colorectal Cancer

Syndromes: FAP
Familial adenomatous polyposis (FAP) accounts for 1% of colorectal
cancer cases
People with FAP typically develop hundreds to thousands of colon
polyps (small growths); the polyps are initially benign
(noncancerous), but there is nearly a 100% chance that the polyps
will develop into cancer if left untreated
Colorectal cancer usually occurs by age 40 in people with FAP
Mutations (changes) in the APC gene cause FAP; genetic testing is
available
Yearly screening for polyps is recommended
Attenuated familial adenomatous polyposis (AFAP) is related to FAP;
people have fewer polyps

Hereditary Colorectal Cancer

Syndromes
Several other less common syndromes can
increase a persons risk of colorectal cancer

Morphology
25% of colorectal carcinomas: in cecum or
ascending colon
similar proportion: in rectum and distal
sigmoid
25%: in descending colon and proximal
sigmoid
remainder scattered elsewhere
multiple carcinomas present often at
widely disparate sites in the colon

Morphology
all colorectal carcinomas begin as in situ lesions
tumors in the proximal colon: polypoid, exophytic
masses that extend along one wall of the cecum and
ascending colon

Morphology
in the distal colon: annular, encircling lesions that
produce napkin-ring constrictions of the bowel and
narrowing of the lumen
both forms of neoplasm eventually penetrate the bowel
wall and may appear as firm masses on the serosal
surface

Morphology
all colon carcinomas - microscopically similar
almost all - adenocarcinomas
range from well-differentiated to undifferentiated,
frankly anaplastic masses
many tumors produce mucin
secretions dissect through the gut wall, facilitate
extension of the cancer and worsen the prognosis
cancers of the anal zone are predominantly squamous
cell in origin

Clinical Features
may remain asymptomatic for years
symptoms develop insidiously
cecal and right colonic cancers:
fatigue
weakness
iron deficiency anemia
left-sided lesions:
occult bleeding
changes in bowel habit
crampy left lower quadrant discomfort
anemia in females may arise from gynecologic causes, but it is a clinical
maxim that iron deficiency anemia in an older man means
gastrointestinal cancer until proved otherwise

Clinical Features
TNM Staging of Colon Cancer

spread by direct extension into

adjacent structures and by
metastasis through lymphatics and
blood vessels
favored sites for metastasis:

regional lymph nodes

liver
lungs
bones
other sites including serosal
membrane of the peritoneal
cavity

carcinomas of the anal region

locally invasive, metastasize to
regional lymph nodes and distant
sites

Tumor (T)
T0 = none evident
Tis = in situ (limited to mucosa)
T1 = invasion of lamina propria or submucosa
T2 = invasion of muscularis propria
T3 = invasion through muscularis propria into
subserosa or nonperitonealized perimuscular
tissue
T4 = invasion of other organs or structures
Lymph Nodes (N)
0 = none evident
1 = 1 to 3 positive pericolic nodes
2 = 4 or more positive pericolic nodes
3 = any positive node along a named blood vessel
Distant Metastases (M)
0 = none evident
1 = any distant metastasis
5-Year Survival Rates
T1 = 97%
T2 = 90%
T3 = 78%
T4 = 63%
Any T; N1; M0 = 66%
Any T; N2; M0 = 37%
Any T; N3; M0 = data not available
Any M1 = 4%

Clinical Features
detection and diagnosis:
digital rectal examination
fecal testing for occult blood loss
barium enema, sigmoidoscopy and
colonoscopy
confirmatory biopsy
computed tomography and other
radiographic studies
serum markers (elevated blood
levels of carcinoembryonic antigen)
molecular detection of APC
mutations in epithelial cells,
isolated from stools
tests under development:
detection of abnormal patterns of
methylation in DNA isolated from
stool cells

Colorectal Cancer and Early Detection

Colorectal cancer can be prevented through
regular screening and the removal of polyps
Early diagnosis means a better chance of
successful treatment
Screening should begin at age 50 for all average
risk individuals or sooner if you have a family
history of colorectal cancer, symptoms, or a
personal history of inflammatory bowel disease

Screening Methods for Colorectal

Cancer
Colonoscopy (currently the best way to prevent and detect
colorectal cancer)
Virtual colonography

Sigmoidoscopy
Fecal occult blood test
Double contrast barium enema
Digital rectal examination

What Are the Symptoms of

Colorectal Cancer?

A change in bowel habits: diarrhea, constipation, or a feeling that

the bowel does not empty completely
Bright red or dark blood in the stool
Stools that appear narrower or thinner than usual
Discomfort in the abdomen, including frequent gas pains, bloating,
fullness, and cramps
Unexplained weight loss, constant tiredness, or unexplained anemia
(iron deficiency)

How is Colorectal Cancer Evaluated?

Diagnosis is confirmed with a biopsy
Stage of disease is confirmed by pathologists
and imaging tests, such as computerized
tomography (CT or CAT) scans
Endoscopic ultrasound and magnetic
resonance imaging (MRI) may also be used to
stage rectal cancer

Cancer Treatment: Surgery

Foundation of curative therapy
The tumor, along with the adjacent healthy
colon or rectum and lymph nodes, is typically
removed to offer the best chance for cure
May require temporary or (rarely) permanent
colostomy (surgical opening in abdomen that
provides a place for waste to exit the body)

Cancer Treatment: Chemotherapy

Drugs used to kill cancer cells
Typical medications include fluorouracil (5-FU),
oxaliplatin (Eloxatin), irinotecan (Camptosar), and
capecitabine (Xeloda)
A combination of medications is often used

Types of Chemotherapy
Adjuvant chemotherapy is given after surgery to
maximize a patients chance for cure
Neoadjuvant chemotherapy is given before
surgery
Palliative chemotherapy is given to patients
whose cancer cannot be removed to delay or
reverse cancer-related symptoms and
substantially improve quality and length of life

Cancer Treatment: Radiation Therapy

The use of high-energy x-rays or other particles to
destroy cancer cell
Used to treat rectal cancer, either before or after
surgery
Different methods of delivery
External-beam: outside the body
Intraoperative: one dose during surgery

New Therapies: Antiangiogenesis

Therapy
Starves the tumor by disrupting its blood
supply
This therapy is given along with chemotherapy
Bevacizumab (Avastin) was approved by the
U.S. Food and Drug Administration (FDA) in
2004 for the treatment of stage IV colorectal
cancer

New Therapies: Targeted Therapy

Treatment designed to target cancer cells
while minimizing damage to healthy cells
Cetuximab (Erbitux) was approved by the FDA
in 2004 for the treatment of advanced
colorectal cancer

Colorectal Cancer Staging

Staging is a way of describing a cancer, such as
the depth of the tumor and where it has spread
Staging is the most important tool doctors have
to determine a patients prognosis
Staging is described by the TNM system: the size
(the depth of penetration of the Tumor into the
wall of the bowel), whether cancer has spread to
nearby lymph Nodes, and whether the cancer has
Metastasized (spread to organs such as the liver
or lung)
The type of treatment a person receives depends
on the stage of the cancer

Stage 0 Colorectal Cancer

Known as cancer in
situ, meaning the
cancer is located in
the mucosa (moist
tissue lining the colon
or rectum)
Removal of the polyp
(polypectomy) is the
usual treatment

Stage I Colorectal Cancer

The cancer has grown
through the mucosa
and invaded the
muscularis (muscular
coat)
Treatment is surgery
to remove the tumor
and some surrounding
lymph nodes

Stage II Colorectal Cancer

The cancer has grown beyond

the muscularis of the colon or
rectum but has not spread to
the lymph nodes
Stage II colon cancer is treated
with surgery and, in some
cases, chemotherapy after
surgery
Stage II rectal cancer is treated
with surgery, radiation therapy,
and chemotherapy

Stage III Colorectal Cancer

The cancer has spread to

the regional lymph nodes
(lymph nodes near the
colon and rectum)
Stage III colon cancer is
treated with surgery and
chemotherapy
Stage III rectal cancer is
treated with surgery,
radiation therapy, and
chemotherapy

Stage IV Colorectal Cancer

The cancer has spread

outside of the colon or
rectum to other areas of
the body
Stage IV cancer is treated
with chemotherapy.
Surgery to remove the
colon or rectal tumor
may or may not be done
Additional surgery to
remove metastases may
also be done in carefully
selected patients

The Role of Clinical Trials for the

Treatment of Colorectal Cancer

Clinical trials are research studies involving people

They test new treatment and prevention methods to
determine whether they are safe, effective, and better
than the best known treatment
The purpose of a clinical trial is to answer a specific
medical question in a highly structured, controlled
process
Clinical trials can evaluate methods of cancer
prevention, screening, diagnosis, treatment, and/or
quality of life

Clinical Trials: Patient Safety

Informed consent: Participants should
understand why they are being offered entry into
a clinical trial and the potential benefits and risks;
informed consent is an ongoing process

Participation is always voluntary, and patients can

leave the trial at any time
Other safeguards exist to ensure ongoing patient
safety

Clinical Trials: Phases

Phase I trials determine safety and dose of a new
treatment in a small group of people
Phase II trials provide more detail about the
safety of the new treatment and determine how
well it works for treating a given form of cancer
Phase III trials take a new treatment that has
shown promising results when used to treat a
small number of patients with cancer and
compare it with the current, standard treatment
for that disease; phase III trials involve a large
number of patients

Clinical Trials Resources

Coalition of Cancer Cooperative Groups
(www.CancerTrialsHelp.org)
CenterWatch (www.centerwatch.com)
National Cancer Institute
(www.cancer.gov/clinical_trials)

Coping With the Side Effects of Cancer

and its Treatment
Side effects are treatable; talk with the doctor or
nurse
Fatigue is a common, treatable side effect
Pain is treatable; non-narcotic pain relievers are
available
Antiemetic drugs can reduce or prevent nausea
and vomiting
For more information, visit
www.plwc.org/sideeffects

Follow-Up Care
Doctors visits
Serial carcinoembryonic antigen (CEA)
measurements are recommended
Colonoscopy one year after removal of colorectal
cancer
Surveillance colonoscopy every three to five years
to identify new polyps and/or cancers
More information can be found in the ASCO
Patient Guide: Follow-Up Care for Colorectal
Cancer