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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)

Each year around 289,000 people are newly diagnosed with cancer and breast, lung, colorectal and prostate

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,

Colorectal Cancer
Colorectal Cancer

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 • peak incidence: 60 to 70 years of age • < 20% cases before age

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
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%
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
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 person’s risk of
Hereditary Colorectal Cancer
Syndromes
• Several other less common syndromes can
increase a person’s 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

frankly anaplastic masses

almost all - adenocarcinomas

range from well-differentiated to undifferentiated,

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

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

TNM Staging of Colon Cancer

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

levels of carcinoembryonic antigen)

computed tomography and other

radiographic studies serum markers (elevated blood

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

• Clinical Features detection and diagnosis: – digital rectal examination – fecal testing for occult blood
• Clinical Features detection and diagnosis: – digital rectal examination – fecal testing for occult blood
Colorectal Cancer and Early Detection • Colorectal cancer can be prevented through regular screening and the
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
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

What Are the Symptoms of Colorectal Cancer?

• A change in bowel habits: diarrhea, constipation, or a feeling that the bowel does not
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
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
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),
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 patient’s chance for cure
• Adjuvant chemotherapy is given after surgery to
maximize a patient’s chance for cure

Neoadjuvant chemotherapy is given before surgery

Types of Chemotherapy • Adjuvant chemotherapy is given after surgery to maximize a patient’s chance for
• Palliative chemotherapy is given to patients whose cancer cannot be removed to delay or reverse
• 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
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
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
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
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 patient’s 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
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
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
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
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
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
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
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
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)
Clinical Trials Resources
• Coalition of Cancer Cooperative Groups
(www.CancerTrialsHelp.org)
• CenterWatch (www.centerwatch.com)

National Cancer Institute (www.cancer.gov/clinical_trials)

Clinical Trials Resources • Coalition of Cancer Cooperative Groups (www.CancerTrialsHelp.org) • CenterWatch (www.centerwatch.com) • National Cancer
Coping With the Side Effects of Cancer and its Treatment • Side effects are treatable; talk

Coping With the Side Effects of Cancer and its Treatment

• Side effects are treatable; talk with the doctor or nurse • Fatigue is a common,
• 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 • Doctor’s visits • Serial carcinoembryonic antigen (CEA) measurements are recommended • Colonoscopy one
Follow-Up Care
• Doctor’s 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