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MINISTRY OF HEALTH OF UKRAINE
VINNITSA NATIONAL PIROGOV MEMORIAL MEDICAL
UNIVERSITY
"CONFIRM"
at the methodical meeting
Department of Ray diagnostics,
Ray therapy and Oncology
Head of the department
As. of Prof., M.S.D. Kostyuk A.G.
________________________
"______" ________ 2013 year
METHODICAL GUIDELINES
For self-study for students in preparing for the practical (seminary) lessons
Subject of Study
Oncology
Module No
1
Theme No
7
Topic of Lesson
Colon cancer.
Risk factors. Classification by TNM. Methods of
diagnostics. Clinics. Treatment: surgery, radiotherapy,
chemotherapy, combined.
Course
5
Faculty
General Medicine
2
Topicality. Colorectal cancer is the third most common malignant tumor and the
fourth most common cause of cancer death in the world. Every year it was estimated
that worldwide there would be 945,000 new colorectal cancer cases and 492,400
colorectal cancer-related deaths.
In the United States every year are expected 106,680 new cases of colon cancer (men
49,220; women 57,460), and 42,000 new cases of rectal cancer (men 23,580; women
18,350). Colorectal cancer is the second leading cause of cancer related death in the
United States with 68,000 deaths annually representing 10% of all cancer deaths.
Age is a major risk factor in developing colon cancer. Increase the risk of developing
colorectal cancer is approximately after age 50.
Learning Objectives:
1 Incidence and epidemiology
2. Etiology and Risk factors.
3. Differential diagnosis between benign tumors and Colon cancer.
4. The ways of spreading Colon cancer.
5. Classification TNM. Stages of Colon cancer.
6. Hystologic Classification Colon tumors.
7. Main symptoms in dependent of localization.
8. Treatment tactics
9. Surgical treatment of Colon cancer in dependent of localization
10. Choice the method of treatment (surgical, chemo- and radiotherapy).
11. Indications and contraindications for chemo- and radiotherapy.
12. Survival and prognosis.
13. Palliative care
Colorectal Cancer
Statistics
In the United States, 106,680 new cases of colon cancer were expected in 2006 (men
49,220; women 57,460) (1), and 41,930 new cases of rectal cancer were expected in
2006 (men 23,580; women 18,350). Colorectal cancer is the second leading cause of
cancer related death in the United States with 68,000 deaths annually representing
10% of all cancer deaths. Age is a major risk factor in developing colon cancer. The
lifetime risk of developing colorectal cancer is approximately 5% with the vast
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majority of cancers occurring after age 50. The overall incidence has been falling
perhaps due to screening.
Epidemiologic Associations The vast majority of colorectal cancers are sporadic and
not familial. Epidemiologic studies demonstrate an increased risk of colorectal
cancer with the following conditions/characteristics:
• Family history of colorectal cancer is associated with an increased risk
ofdeveloping colorectal cancer. If one first-degree family member had colorectal
cancer, the risk increases 1.7-fold
• Western/urbanized societies
• Diet high in red or processed meat
• Increased bowel anaerobic flora
• Diabetes mellitus/insulin resistance: the risk of colon cancer may be 30% higher in
diabetics compared with nondiabetics
• Inflammatory bowel disease. Increased incidence is seen with both Crohn’s disease
and ulcerative colitis and is associated with the severity, extent, and duration of
disease affecting the colon. The risk of colon cancer in ulcerative colitis is
approximately 10% at 10 year duration, 20% at 20 year duration, and >35% at 30
year duration. Total colectomy eliminates the risk of colon cancer.
• Cigarette smoking
• Alcohol consumption
• Ureterosigmoidostomy
• Streptococcus bovis bacteremia
• Prior pelvic radiation
RISK FACTORS
DIETARY
A typical Western diet consists of increased intake of fats and red meats, and
decreased fruit and vegetable intake. Epidemiologic studies suggest a relationship
between lifestyle, diet, and colorectal cancer risk. Modifying dietary and lifestyle
factors could help in the prevention of colorectal cancer as well as provide other
health benefits.
ALCOHOL AND TOBACCO
Daily alcohol consumption increases the risk of colon cancer. There is a twofold
increase in risk of colon cancer in individuals who consume greater than two drinks
per day. Beer intake has been suggested to increase risk of CRC, mainly of rectal
cancer
PHYSICAL ACTIVITY AND TOTAL BODY MASS
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There is a definite relationship between physical activity and decreased colon cancer
risk, but not rectal cancer risk.
NONSTEROIDAL ANTIINFLAMMATORY DRUGS
Nonsteroidal antiinflammatory drug (NSAID) use is associated with a decreased risk
of colorectal cancer. The majority of the epidemiologic studies in the literature reveal
that there is a decrease in adenoma incidence, carcinoma incidence, and colorectal
cancer mortality associated with NSAID use. The use of aspirin for at least 16 days
per month reportedly reduces colorectal cancer risk by 50% and reduces the risk of
colorectal cancer death by 40%.
Age
The incidence of colorectal cancer increases after age 50 years. In the Surveillance,
Epidemiology and End Results statistics for the period 1995 to 1999, the incidence
rate of colorectal cancer was 48 per 100,000 population for individuals between 40
and 49 years of age, while it was 327 per 100,000 population for individuals aged 60
to 69 years. The incidence rate increased with each subsequent decade age.
Prior History of Adenomas A personal history of adenomas will increase the risk of
subsequent adenomas and thus of colorectal cancer.
Family History of CRC and Adenomas
Family history of colorectal cancer in a firstdegree relative increases the risk of
colorectal cancer two- to threefold
Prior History of Colorectal Cancer
After curative resection, patients with colorectal cancer are at risk of recurrent
disease. However, the main purpose of endoscopic surveillance is to detect
metachronous lesions. The incidence of metachronous colorectal cancer and
adenomas in patients with a personal history of CRC is approximately 6% and 25%,
respectively.
Hereditary Nonpolyposis Colorectal Cancer
HNPCC is an autosomal dominant syndrome characterized by early age onset of
colorectal cancer, right-sided predominance, excess synchronous and metachronous
colorectal neoplasms, and extracolonic malignancies such as endometrial cancer,
small-bowel cancer, renal, pelvis, and ureter cancers, and skin lesions such as
sebaceous adenomas, keratoacanthomas, and sebaceous carcinoma. The median age
of onset of CRC is 45 years.
Hamartomatous Polyposis Syndromes
Peutz-Jeghers and juvenile polyposis are the most common hamartomatous polyposis
syndromes predisposing to colorectal cancer. Peutz-Jeghers patients are also at risk
of stomach, pancreas, breast, and uterine carcinoma, as well as ovarian sex cord
tumors. In addition to colorectal cancer, juvenile polyposis patients are at risk of
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gastric, duodenal, and pancreatic cancers. In both of these syndromes, there are no
evidence-based surveillance recommendations. The recommendations have to be
individualized. Genetic testing is also available for affected patients.
Crohn Disease
The incidence and characteristics of colorectal cancer in Crohn disease have been
reported to be similar to ulcerative colitis. There are no specific recommendations for
surveillance in Crohn disease. However, following the model of ulcerative colitis,
recommendations can be made for colonoscopy after 8 years of diagnosis and then
every 1 to 2 years. Consideration should be given to random biopsies every 10 cm.
Ulcerative Colitis
In a meta-analysis of 116 publications in the English language, was noted that the
annual colonoscopy should be performed after 8 years of pancolitis. If the disease is
confined to the left side of the colon, then surveillance can be started at a later time.
It is imperative to perform random biopsies every 10 cm. If there is severe dysplasia
in the specimens, consideration should be given to surgery, as there is a high
incidence of occult cancer in the colon.
Development of Colorectal Cancer from Polyps
Most colorectal cancers arise from adenomatous polyps. The progression of
adenomatous polyps from small polyps, to larger polyps, to dyspastic polyps, and
finally to cancer occurs over at least a 10 year period. Colonoscopy is best method
allows for direct visualization of the colon and, if necessary, polypectomy.
Approximately 3–6% of Americans undergoing colonoscopic screening in their 50s
will have a colon cancer, dysplastic polyp, or villous adenoma.
For patients without a family history of colon cancer, the United States Multisociety
Task Force recommends screening patients beginning at age 50 with annual fecal
occult blood test as well as sigmoidoscopy every 5 years.
For patients with two or more affected first-degree relatives or any firstdegree
relative with colon cancer under the age of 60, screening should begin by age 40 or at
least 10 years younger than the age at which the affected family member was
diagnosed.
Pathology of Primary Tumors
Approximately 95% of the malignant colorectal tumors are adenocarcinomas.
Macroscopically, colorectal tumors can be described as ulcerative, polypoid, or
infiltrative. Histopathologically, colorectal adenocarcinomas are classified as well,
moderately, or poorly differentiated, depending on the formation of glandular
elements. Well and moderately differentiated adenocarcinomas have more glandular
components than do poorly differentiated tumors.
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Adenocarcinomas of the colon and rectum are also described depending on
additional cytological and histopathologic characteristics. Mucin-producing tumors
characterized by extracellular mucin pools. Signet-ringcell–type adenocarcinomas
characteristically have intracellular mucin pushing the nuclei to give the cell the
characteristic signet ring appearance. Adenosquamous carcinomas are composed of
both glandular and squamous elements.
PRESENTATION AND STAGING
Signs and Symptoms
The presenting symptoms depend on the location of the tumor. Obstruction,
perforation, change in stool character, and hematochezia are more common with leftsided tumors. Anaemia is more common features right-sided tumors related.
The most common symptoms of large bowel cancer are a change in bowel habits
(constipation or diarrhoea or sometimes alternating constipation and diarrhoea),
bleeding from the bowel, and a feeling of incomplete evacuation after going to the
toilet. In some cases patients are not aware of any symptoms until the cancer has
caused partial or complete bowel obstruction. The fi rst symptoms may thus be of
bowel obstruction with intermittent griping abdominal pain (colic), constipation and
abdominal distension.
Other features of large bowel cancer may be of general debility, weight loss,
tiredness and lassitude (sometimes due to anaemia) or features of liver enlargement
or jaundice due to liver metastases. It may be possible to feel an abdominal lump or
localised swelling or on anal examination with a gloved finger, a mass in the anus or
lower rectum can sometimes be felt. There may be evidence of blood in the faeces. In
obstructive bowel cancer, colic with abdominal distension or swelling is likely.
Staging of Colon Cancer
The process of staging a colon cancer is based on the American Joint Committee on
Cancer (AJCC) TNM.
T (Tumor) CATEGORIES FOR COLORECTAL CANCER
The T stage describes the extent through the bowel wall that the cancer spread. The
N (Nodes) stage describes the presence of regional nodal metastases
Tx. No description of the tumor’s extent is possible because of incomplete
information.
Tis. The cancer is in the earliest stage. It involves only the mucosa. It has not grown
beyond the muscularis mucosa (inner muscle layer) of the colon or rectum. This
stage is also known as carcinoma in situ or intramucosal carcinoma.
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T1. The cancer has grown through the muscularis mucosa and extends into the
submucosa.
T2. The cancer has grown through the submucosa, and extends into the muscularis
propria.
T3. The cancer has grown completely through the muscularis propria into the
subserosa but not to any neighboring organs or tissues.
T4. The cancer has spread completely through the wall of the colon or rectum into
nearby tissues or organs.
N CATEGORIES FOR COLORECTAL CANCER N categories indicate whether or
not the cancer has spread to nearby lymph nodes and, if so, how many lymph nodes
are involved.
Nx. No description of lymph node involvement is possible because of incomplete
information.
N0. No lymph node involvement is found.
N1. Cancer cells found in one to three regional nodes. Regional nodes depend upon
the location of the colon cancer and are located along the course of major vessels
supplying the colon, along the vascular arcades of the marginal artery, and along the
mesocolic border of the colon.
N2. Cancer cells found in four or more regional lymph nodes.
M CATEGORIES FOR COLORECTAL CANCER M categories indicate whether or
not the cancer has spread to distant organs, such as the liver, lungs, or distant lymph
nodes.
Mx. No description of distant spread is possible because of incomplete information.
M0. No distant spread is seen.
M1. Distant spread is present.
TREATMENT
Surgical Management
At presentation, the initial evaluation should consist of routine chemistries and a
complete blood count. An elevated carcinoembryonic antigen (CEA) preoperatively
is associated with a poor prognosis. The routine use of imaging is controversial. It is
reasonable to obtain CT scans of the chest, abdomen, and pelvis to evaluate for the
presence of metastatic disease.
For patients with stage I, II, or III colon cancer, surgical resection of the colon cancer
is the mainstay of therapy. Open colectomy or laparoscopic colectomy is equally
effective. For patients with stage IV colon cancer who are not considered candidates
for cure, resection of the primary lesion can be based upon the symptoms of the
patient. In the asymptomatic patient, surgical resection of the primary tumor is not
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necessary and can be deferred until the patient experiences local symptoms. Some
patients will die of metastatic disease without ever experiencing symptoms from the
primary tumor.
Stage 1
Surgical resection cures >90% of patients with stage 1 colon cancer. Adjuvant
therapy is not recommended. Patients should undergo surveillance colonoscopy
within 3–5 years of diagnosis. Patients with more than two firstdegree relatives with
colon cancer, a first-degree relative with colon cancer under the age of 50, or who are
under 50 themselves, should undergo evaluation in a genetic/high-risk clinic.
Stage 2
Surgical resection cures approximately 80% of patients with stage 2 colon cancer.
The use of adjuvant chemotherapy is controversial and is currently not recommended
by the American Society of Clinical Oncology. Randomized studies have not shown
a statistically significant benefit for the use of adjuvant chemotherapy in patients
with stage 2 colon cancer. However, many experts advocate for the use of adjuvant
chemotherapy in high-risk patients, because these patients carry a greater than 20%
risk of dying from recurrent disease. Patients with stage 2 colon cancer who are
considered high risk carry the following features
• T4 disease
• Presentation with perforation or obstruction
• Inadequate nodal evaluation; the American College of Pathology recommends that at least 12 regional lymph nodes be examined for the presence of
nodal metastases
• Poorly differentiated tumors
For type of adjuvant chemotherapy see stage 3 section below.
Stage 3
Surgical resection cures approximately half of patients with stage 3 colon cancer.
Patients with N1 disease can expect a cure rate with surgery alone of approximately
60–70%. Patients with N2 disease can expect a cure rate of 30% with surgery alone.
Adjuvant chemotherapy is recommended for all patients with stage 3 colon cancer at
improved overall survival.
Standard treatment can consist of 6 months of 5-fluorouracil (5FU) and leucovorin.
Six months of capecitabine, an oral fluoropyrimidine, has equivalent efficacy to
intravenous 5FU and leucovorin. Recently, the addition of oxaliplatin to intravenous
5FU and leucovorin has been associated with an improved disease-free survival
compared with 5FU and leucovorin for patients with stage 2 and 3 colon cancer.
Subset analysis of patients with stage 2 disease did not reveal a statistically
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significant advantage in disease-free survival for patients receiving FOLFOX
compared with 5FU and leucovorin.
Stage 4
All patients with isolated liver or lung metastases should be evaluated by a surgical
specialist for consideration of resection of the metastases. Approximately 30% of
patients undergoing complete resection of isolated liver or lung metastases will be
cured.
For patients in whom a curative resection cannot be done, the median survival is
approximately 6–8 months without chemotherapy and 2 years with chemotherapy.
Approximately 10% of patients who undergo aggressive chemotherapy will live for 5
years.
Until 1997, 5FU was the only active chemotherapy. Studies demonstrated that the
addition of folinic acid (leucovorin) to 5FU improved the response rates and time to
tumor progression. Since 1997, irinotecan, oxaliplatin, bevacizumab, and cetuximab
have been approved for use in patients with metastatic colon cancer.
First-line chemotherapy for patients with metastatic disease of consists of either
FOLFOX (5FU, leucovorin, oxaliplatin) or FOLFIRI (5FU, leucovorin, irinotecan)
with bevacizumab. Second-line chemotherapy typically consists of either an
irinotecan-based regimen if FOLFOX was used as the first-line regimen, and an
oxaliplatin-based regimen if FOLFIRI was used as the first-line regimen. Cetuximab
is approved for use either alone or in combination with irinotecan for patients who
had previously progressed on an irinotecan containing regimen. Capecitabine is often
substituted for 5FU and leucovorin in the FOLFOX regimens. The median survival
for patients with metastatic disease receiving all available therapy is approximately 2
years
Suggested Reading:
1. Manual Of Clinical Oncology, - Dennis A. Casciato, Barry B. Lowitz, 2000
2. Oxford Handbook of Oncology, - Oxford University Press, 2002
3. Basics of Oncology, - Frederick O. Stephens · Karl R. Aigner, 2009
4. HARRISON’S Manual of Oncology, - Bruce A. Chabner, Thomas J. Lynch,
Jr., Dan L. Longo, 2008