cancer colon cancer epidemiology, treatment, and survival david geffen ucla school of medicine 2007...

Cancer

Colon Cancer Epidemiology, Treatment, and Survival

David Geffen UCLA School of Medicine2007 Cancer Survivorship GrantAuthors: Wendy Liu, James S. Tomlinson, M.D.

Goals of this ModuleThis is an interactive and self-directed learning module intended to build a foundation of knowledge around the epidemiology, diagnosis, treatment and survival of colon cancer patients. You will be presented with a patient case and a series of related questions. You may continue with the case upon correctly answering each question. However, we encourage you to select each of the answer choices for further explanations. Additional hyperlinks are available throughout the case providing access to related topics and journal articles. Please remember that passage to continue with the case is from the correct answer slide.

Begincase

Colon Cancer Module

Mr. Jackson is a 61 year old male who comes to see you, his primary care doctor, complaining of “feeling tired” and just wants a check-up. He saw a doctor at the urgent care clinic last week who sent some labs and made this follow up appointment for him. He further states that his uncle recently passed away secondary to metastatic colon cancer diagnosed at age 86 and this event has made him somewhat depressed and anxious about having cancer. He reports that he had a colonoscopy at age 51 during which a nonmalignant small (1cm) polyp was removed from his colon.

Next

Colon Cancer Module

Colon Cancer

Colon cancer is the second most common cause of cancer deaths in the United States. It constitutes approximately 10% of all new cancer cases and has an estimated annual incidence of 150,000 new cases in the United States. The estimated deaths from colon cancer exceeds 50,000 per year, which represents approximately 10% of all cancer deaths in the United States.

NextEpidemiology article

Average risk (sporadic; no identifiable risk factor) 75%

Family history of colon cancer 15 to 20%

Hereditary non-polyposis colorectal cancer (HNPCC) 3 to 8%

Familial adenomatous polyposis (FAP) 1%

Ulcerative Colitis 1%

As you can see, the majority of colon cancer cases are considered sporadic, i.e. no identifiable risk factor.

Colon Cancer Module

Incidence of Colon Cancer by Risk Category

Question#1

Hereditary colon cancer article

Colon Cancer Module

A. Age

B. Gender

C. Uncle diagnosed with colon cancer at age 86

D. Endoscopic polypectomy at age 51

Question #1. Which of the following factors, independently, has the greatest impact on Mr. Jackson’s risk for developing colon cancer?

Colon Cancer Module

Question #1. Correct!A. Age

Age is a major, independent risk factor for developing colon cancer. It has been well documented that the incidence of colon cancer increases with age. SEER (Surveillance, Epidemiology, and End Results) data indicates that less than 6% of cases develop before age 50. After age 50, the incidence steadily increases.

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Return toQuestion #1

Ahnen DJ. “Epidemiology and risk factors for colorectal cancer.” June 2007. Jan. 2008. <http://www.uptodate.com>.

Colon Cancer Module

Question #1. Incorrect

B. Gender

According to SEER data, male gender is associated with a higher incidence of colon cancer, across all racial and ethnic groups. The incidence of colon cancer is 64.2 per 100,000 in men compared to 46.7 per 100,000 in women. Observed death rates for colon cancer are also higher in males. Nevertheless, gender as a risk factor alone, has not been incorporated into screening guidelines.


Colon Cancer Module


C. Uncle diagnosed with colon cancer at age 86

About 15-20% of all colon cancer cases are associated with a positive family history. Most guidelines recommend earlier and more frequent screening for patients with family history of colon cancer in > 1 first-degree relative(s), especially if diagnosed prior to age 60. Mr. Jackson’s uncle (not considered a first degree relative) was diagnosed with colon cancer at an older age (>60). This does not significantly alter his risk of developing colon cancer and he is still considered to be at “average” risk for developing colon cancer.


Colon Cancer Module


D. Endoscopic polypectomy at age 51

Patients with adenomatous polyps have an increased risk of developing colon cancer. Endoscopic polypectomy and surveillance has been shown to significantly reduce subsequent colon cancer incidence. In fact, the subsequent risk of developing colon cancer after polypectomy (non-sessile, small size) does not exceed that of the general population.


Polypectomy article

Colon Cancer Module

Colon Cancer Risk Factors Age: Approximately 95% of colon cancer cases occur after age 50. The risk increases steadily with advancing age. Colon cancer screening is generally advised for men and women > 50 years old.

Next Risk Factor

Ahnen DJ. “Epidemiology and risk factors for colorectal cancer.” June 2007. Jan. 2008. <http://www.uptodate.com>.

Colon Cancer Module

Colon Cancer Risk Factors

Symptoms and signs: Patients who experience any rectal bleeding, any unexplained persistent change in bowel habits or stool character, or found to have iron deficient anemia should be referred for colonoscopy.

Next Risk Factor

Colon Cancer Module

Colon Cancer Risk Factors Family History: 15-20% of all colon cancer cases are associated with a positive family history. The number of affected first-degree relatives and their age of diagnosis affect a patient’s risk for colon cancer. A family history of early onset colon cancer should prompt suspicion for hereditary colon cancer syndromes. A general rule of thumb is to begin screening approximately 10 years earlier than the youngest age of diagnosis in a first degree relative.

Next Risk FactorHereditary colon cancer article

Colon Cancer Module

Colon Cancer Risk Factors Past medical history:

• Patients with a personal history of colon cancer are at increased risk for developing a second primary colon cancer.

• Patients with inflammatory bowel disease for > 8-10 years in duration are at an increased risk for developing colon cancer.

Next Risk Factor

Colon Cancer Module

Colon Cancer Risk Factors

Other risk factors: Male gender, obesity, current smoking, and heavy alcohol intake are associated with increased colon cancer risk, but are not part of current screening guidelines.

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Colon Cancer Module

Colon Cancer Screening Terminology

• Screening is the testing of an asymptomatic population considered to be at average risk for a disease. The goal of a screening test is to detect a disease at a stage when intervention may significantly improve outcome.

• People are considered to be at average risk if they are > 50 years old and have no other risk factors

• Screening tests should not be offered to individuals with symptoms/signs suggestive of cancer. They should be offered prompt diagnostic evaluation.

Question#2

Colon Cancer Module

Question #2: It appears Mr. Jackson had some sort of colon cancer screening when he was 51 years of age. What are the current screening recommendations for the average risk individual in the United States?

A. Annual Fecal Occult Blood Test (FOBT) starting at age 40

B. Biennial FOBT starting at age 40

C. Annual FOBT starting at age 50

D. Colonoscopy every 3 years starting at age 50

E. CT colonography every 5 years starting at age 50

Colon Cancer Module


A. Annual Fecal Occult Blood Test (FOBT) starting at age 40

For average risk patients, screening for colon cancer should start at age 50.


Colon Cancer Module


B. Biennial FOBT starting at age 40

For average risk patients, screening using FOBT should be once a year, starting at age 50.


Colon Cancer Module

Question #2. Correct!

C. Annual FOBT starting at age 50

For average risk patients, screening using FOBT should be once a year, starting at age 50. Any positive FOBT should be promptly followed by further diagnostic evaluation such as a colonoscopy.


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Colon Cancer Module


D. Colonoscopy every 3 years starting at age 50

Colonoscopy is considered the gold standard in colon cancer screening because it is the only test that is both diagnostic and therapeutic. It can simultaneously examine the entire colon accurately, remove any polyps, and biopsy any suspicious lesions. As a screening test, colonoscopy is recommended every 10 years starting at age 50.

More frequent colonoscopy exams, such as every 3 years, increases the associated exam risks, such as bowel perforation without a proven screening benefit. Return to

Question #2

Colon Cancer Module

Question #2. IncorrectE. CT colonography

CT colonography is currently not recommended as a screening test for colon cancer. A recent study compared the efficacy of CT colonography as a colon cancer screening tool in average risk adults against colonoscopy. The study found that the two tests had similar detection rates for advanced adenomas and invasive cancers, but the colonoscopy cohort had significantly more polyps removed than the CT colonography cohort who subsequently were referred for polypectomy. More studies are needed to better define the role of CT colonography in colon cancer screening.


CT colonography article

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Colon Cancer Screening

Next

Beginning at age 50, men and women at average risk for developing colon cancer should be offered one of the following screening options. These options differ in regard to evidence of effectiveness, cost, risk, and availability. As a result, presenting patients with multiple screening options allows individualized care and may increase the likelihood that screening will occur.

Average Risk

• Fecal occult blood testing (FOBT) every year (Follow up any positive with colonoscopy)

• Flexible sigmoidoscopy every 5 years

• FOBT every year plus flexible sigmoidoscopy every 5 years

• Colonoscopy every 10 years

• Double contrast barium enema every 5 years

Screening article

Colon Cancer Module

Colon Cancer Screening Positive Family History

Next

Average Risk

Individuals with only one first-degree relative with colon cancer diagnosed at age 60 or later are still considered to be at average risk for developing colon cancer and should be offered the same screening options as the average risk patient.

Increased RiskIndividuals with a first-degree relative diagnosed with early onset colon cancer (prior to age 60) or with multiple first-degree relatives (> 2) with colon cancer at any age are considered as increased risk individuals. They should be advised to have screening colonoscopy, beginning at age 40, or 10 years earlier than the youngest diagnosis in the family, whichever comes first. Screening colonoscopy should be performed at 5-10 year intervals

Colon Cancer Module

Color Cancer Screening

Question#3

FAP

Patients with a diagnosis of Familial Adenomatous Polyposis are at increased risk for developing colon cancer and should receive endoscopic surveillance annually, beginning at age 10-12.

Increased Risk: Hereditary Syndromes

HNPCC

Patients with a diagnosis of Hereditary Nonpolyposis Colorectal Cancer syndrome are at increased risk for colon cancer and should receive colonoscopy, every 1-2 years, beginning at age 20-25 or 10 years younger than the earliest colon cancer diagnosis in the family, whichever comes first.

Hereditary colon cancer article

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Question #3: What is the level of evidence to support the use of FOBT as an initial screening test for colon cancer?

A. Level 1 evidence: supported by Randomized Controlled Trials (RCT)

B. Level 2 evidence: supported by case-control or cohort studies

C. Level 3 evidence: supported by non-analytic studies, including case reports, case series

D. Level 4 evidence: supported by expert opinions

Colon Cancer Module


A. Level 1 evidence: supported by Randomized Controlled Trials (RCT)

FOBT has been shown in 3 RCTs to reduce risk of death from colon cancer.


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B. Level 2 evidence: supported by case-control or cohort studies



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C. Level 3 evidence: supported by non-analytic studies, including case reports, case series



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D. Level 4 evidence: supported by expert opinion



Colon Cancer Module

On exam Mr. Jackson is noted to be overweight (221lbs, 5 ft 10inches). Abdominal exam demonstrated a nontender, nondistended abdomen with no obvious masses. On digital rectal exam the sphincter tone is normal and no the sphincter tone is normal and no masses are noted. The prostate margins are masses are noted. The prostate margins are distinct and it appears to be normal in size. His distinct and it appears to be normal in size. His labs demonstrate a mild anemia (hematocrit = labs demonstrate a mild anemia (hematocrit = 32%) On further questioning, he admits that his 32%) On further questioning, he admits that his stools have been slender in size and lately have stools have been slender in size and lately have been very dark in color.been very dark in color.

Question#4

Physical Exam

Colon Cancer Module

Question #4: Given Mr. Jackson’s anemia coupled with a change in his stool character, you are highly suspicious of a diagnosis of colon cancer. What is the next test you would like to order for Mr. Jackson to help “rule in” or “rule out” a diagnosis of colon cancer?

A. CEA level

C. Flexible sigmoidoscopy

D. Colonoscopy

B. Fecal Occult Blood Test

Colon Cancer Module


A. CEA level

Although serum CEA is often elevated in patients with colon cancer, it can also be elevated in other types of adenocarcinomas and benign disorders. Additionally, some patients with colon cancer do not have elevated CEA level. As a result, serum CEA level is not used in the screening or diagnosis of colon cancer. Rather, CEA is a tool used in the surveillance for colon cancer recurrence after surgical resection of the primary tumor. Its power lies in the ability to monitor efficacy of therapy and to detect cancer recurrence. Return to

Question #4

Colon Cancer Module


B. Fecal Occult Blood Test

The patient’s history of dark black stools is suggestive of GI bleeding. Although ordering a FOBT would confirm GI bleeding, the test result, whether positive or negative, would not negate the need for colonoscopy. This is an example of a test that does not alter management and therefore is of little value in clinical decision making. In considering any test or intervention, a responsible healthcare provider should assess whether the result would affect the management and well being of the patient. This is particularly important when dealing with tumor markers and genetic testing.


Colon Cancer Module

Question #4. IncorrectC. Flexible sigmoidoscopy

Mr. Jackson’s recent change in stool character is suspicious for colon cancer. Flexible sigmoidoscopy refers to an endoscopic examination that is limited to the distal colon up to approximately the splenic flexure. This includes the rectum, sigmoid colon and left colon. Normal findings on Flexible sigmoidoscopy does not rule out malignancy in proximal regions of the colon including the transverse colon and the ascending colon or right side of the colon. Furthermore, even when a lesion is detected by sigmoidoscopy, a colonoscopy is still required to search for synchronous neoplasms in the proximal colon. Return to

Question #4

Colon Cancer Module


D. Colonoscopy

Patients over the age of 50 who report visible rectal bleeding of any type, unexplained iron deficiency anemia, unexplained persistent change in bowel habits or stool character should be referred for colonoscopy. Mr. Jackson’s stool has become slender and very dark recently. The diagnosis of colon cancer should be suspected. Colonoscopy allows for both visualization of the entire colon, removal of any polyps, and biopsy of any suspicious lesions


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Colon Cancer Module

Mr. Jackson states that he does not want to go through a colonoscopy again and wants to know if there are any other test he could do instead. You explain to Mr. Jackson that a colonoscopy is currently the gold standard for evaluation of the colon. Other tests could be done but cannot replace the need for colonoscopy. You explain that he will have to undergo a “bowel prep” which consists of drinking a solution that acts as a cathartic to empty the colon of any stool. This allows the visualization of the entire mucosal surface of the colon during colonoscopy. In addition he will need to remain on a liquid diet the night before colonoscopy.

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Colon Cancer Module

Mr. Jackson undergoes a colonoscopy and returns to your clinic to discuss the results. The report states that a 1 cm tubular adenoma was removed from the transverse colon, i.e. a polypectomy. Furthermore, a 4 cm sessile ulcerated mass was noted in the left colon. The biopsy of this mass revealed moderately differentiated colonic adenocarcinoma.

Question#5

http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=45648

Colon Cancer Module

Question #5: You report the unfortunate news to Mr. Jackson that he has colon cancer. He immediately asks what is the next step?

D. Clinical staging

B. Chemotherapy

A. Surgical resection

C. Radiation therapy

Colon Cancer Module


A. Surgical resection

Although surgery represents the primary treatment modality for most colon cancers, staging work up must be performed preoperatively to determine if the patient is a surgical candidate. For example, if the tumor has already spread to Mr. Jackson’s liver and lungs, localized therapy such as surgical resection of the primary tumor does not ultimately affect survival. It would make more sense to offer chemotherapy to treat the systemic nature of the disease.


Colon Cancer Module

Question #5. IncorrectB. Chemotherapy

Extent of disease / staging work up is the most important initial step in determining optimal therapy for Mr. Jackson. If Mr. Jackson proves to have metastatic disease then chemotherapy as a first line of treatment would be indicated. In the metastatic setting, use of chemotherapy is referred to as “palliative chemotherapy.” Use of chemotherapy after resection of node-positive (Stage III) colon cancer is referred to as “adjuvant chemotherapy” because it is given after surgical resection of the primary tumor.


Colon Cancer Module


C. Radiation therapy

Radiation therapy (RT) alone is not recommended in the treatment of colon cancer. RT may be added to adjuvant chemotherapy on a case-by-case basis for patients at increased risk for recurrence (e.g. T4 tumors) after resection of primary tumor. Of note, RT plays an important role in the preoperative and postoperative management of rectal cancers.


Colon Cancer Module


D. Clinical staging


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Staging is the process that evaluates the local and distant extent of cancer at time of diagnosis. Cancer staging is the most important initial step in selecting the optimal treatment modality and predicting outcome. For colon cancer, the preoperative clinical stage is first determined using information from physical exam, CT scan of the abdomen/pelvis, and chest x-ray, in order to look for evidence of distant metastases. Subsequently, the postoperative pathological stage is determined based on histologic evaluation of the resected tumor and regional lymph nodes.

Colon Cancer Module

Extent of disease or staging workup for Mr. Jackson is completed. Physical exam is negative for ascites, hepatomegaly, and lymphadenopathy. The CT scan of the abdomen and pelvis is negative for any evidence of metastases or other abnormalities. The Chest X-Ray is also negative for abnormalities. CEA level is noted to be 14ng/ml. You inform Mr. Jackson that he does not have evidence of spread of his cancer and that he will need to have surgery to remove his colon cancer.

Question#6

Colon Cancer Module

Question #6: Mr. Jackson first wants to know is a CEA of 14 ng/ml good or bad?

A. Good

C. Neither

B. Bad

Colon Cancer Module


A. Good

Some studies have shown a correlation between elevated preoperative CEA levels (> 5 ng/mL) and heavier disease burden in colon cancer, while other studies found no such association. In Mr. Jackson’s case, although a preoperative CEA of 14ng/ml may suggest a worse prognosis, it alone does not change the treatment plan. The TNM staging remains the most important tool in establishing prognosis and directing therapy.


Colon Cancer Module


B. Bad

Some studies have shown a correlation between elevated preoperative CEA levels (> 5 ng/mL) and heavier disease burden in colon cancer, while other studies found no such association. In Mr. Jackson’s case, although a preoperative CEA of 14 may suggest a worse prognosis, it alone does not change the surgical plans. The TNM staging remains the most important tool in establishing prognosis and directing therapy.


Colon Cancer Module

Question #6. Correct!C. Neither

Elevated preoperative CEA level has been found in several studies to correlate with worse outcome. As a result, the Joint Committee on Cancer and the College of American Pathologists recommend obtaining a this information in addition to TNM staging. However, a CEA of 14 alone would not alter surgical plans. Further, with complete resection, CEA level should return to baseline, and be followed regularly for early detection of recurrence. Thus, postoperatively, the CEA trend is more important than the absolute value.


Question #7

Colon Cancer Module

Question # 7: Mr. Jackson is clinically cleared for surgery. Keeping in mind that Mr. Jackson’s colonoscopy revealed a 1 cm tubular adenomatous polyp that was removed from the ascending colon and a 4 cm colon cancer located within the left colon. What operation will Mr. Jackson need?

A. Left Hemicolectomy

B. Right Hemicolectomy

C. Total Colectomy

D. Abdominoperineal Resection (APR)

Colon Cancer Module


A. Left Hemicolectomy

Two separate lesions were noted during Mr. Jackson’s colonoscopy. The first is a single small tubular adenomatous polyp which is virtually always benign. Endoscopic removal is considered curative, negating the need for surgical resection of the portion of the colon of the proximal or right colon. The second is a left-sided malignant lesion, not involving the rectum (>12 cm from anal verge). A left hemicolectomy is an appropriate surgical option.


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See image of Left hemicolectomy

Colon Cancer Module


B. Right Hemicolectomy

The malignant lesion is left-sided, requiring at minimum a left hemicolectomy. The right-sided small tubular adenomatous polyp is virtually always benign. Endoscopic removal is considered curative, negating the need for a right hemicolectomy.


See image of Right hemicolectomy

Colon Cancer Module


C. Total Colectomy

Although a total colectomy would remove the malignant lesion, it is overly aggressive in this case with significantly increased morbidity and mortality. The right-sided small tubular adenomatous polyp is virtually always benign. Endoscopic removal is considered curative, negating the need for a right hemicolectomy. The malignant lesion is left-sided, therefore a left hemicolectomy would be sufficient.

Return to

Question #7

Colon Cancer Module


D. Abdominoperineal Resection (APR)

APR is a surgical operation used for the treatment of low rectal cancers that are invading the anal sphincter complex. It involves the removal of the anus, the sphincter complex, the rectum, part of the sigmoid colon and their draining lymph nodes. This operation necessitates the need for a colostomy, a surgical opening made between the large intestine and the skin, so that stool can pass through and drain into a colostomy bag.


See image of APR

Colon Cancer Module

Mr. Jackson undergoes a left hemicolectomy and you visit him on postoperative day number 2. He is doing well recovering from his operation and wants to know if he will need any additional treatment. You explain to him that further treatment decisions will depend on the pathologic “staging” information which is based on the pathology report. Normally it takes approximately 7 days for a pathologist to review all of the necessary information and finalize a report.

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Colon Cancer Module

Next

Staging provides a universal language among healthcare providers to allow stratification of patients according to biology and disease burden. This enables the selection of individulaized treatment based on prognostic information associated with a particular “stage group” of the cancer. The Stage group is determined by the combination of pathologic factors “T-N-M”.

American Joint Committee on Cancer (AJCC) T-N-M Staging System for Colorectal Cancer

“T” is usually a measure of tumor size“N” represents the status of the regional lymph nodes with respect to whether or not they contain adenocarcinoma “M” represents presence of metastatic disease

Colon Cancer Module

AJCC Staging System for Colorectal Cancer

See pathologyreport

Primary Tumor (T)

TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ; intraepithelial or invasion

of lamina propria T1 Tumor invades submucosa T2

Tumor invades muscularis propria T3 Tumor invades through the muscularis propria into the subserosa, or into non-

peritonealized pericolic or perirectal tissues T4

Tumor directly invades other organs or structures, and/or perforates visceral peritoneum

Regional Lymph Nodes (N)

NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in 1 to 3 regional lymph nodes N2 Metastasis in 4 or more regional lymph

nodes

Distant Metastasis (M)

MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis

Stage Grouping

Stage T N M0 Tis N0 M0

I T1N0 M0

T2 N0 M0

IIA T3N0 M0

IIBT4 N0 M0

IIIA T1-T2

N1 M0

IIIB T3-T4 N1M0

IIIC Any T N2 M0 IV Any T

Any N M1

Colon Cancer Module

Mr. Jackson continues to do well and on postoperative day #7 the pathology report is available:

• Moderately differentiated adenocarcinoma of colonic origin

• Tumor is 4 cm x 3 cm x 3 cm. Tumor extends through through the muscularis propria into the subserosa

• Proximal and distal colonic margins are free of tumor. Closest margin is 10 cm.

• 2 out of 12 regional lymph nodes were positive for metastatic adenocarcinoma

Question#8

Pathology Report

Colon Cancer Module

Question # 8: What is the stage of Mr. Jackson’s colon cancer?

A. Stage I

B. Stage II

C. Stage III

D. Stage IV

See AJCC staging table

See pathologyreport

Colon Cancer Module


A. Stage I

According to the TNM system, Mr. Jackson’s cancer is T3 (tumor extends to serosa), N1 (2 positive regional lymph nodes), and M0 (no evidence of distant metastases), corresponding to stage IIIb.


Colon Cancer Module


B. Stage II



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C. Stage III



Question#9

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D. Stage IV



Colon Cancer Module

Question #9: What is Mr. Jackson’s predicted 5 year survival rate based on his stage?

A. 20% 5 year survival rate

B. 40% 5 yr survival rate

C. 60% 5 yr survival rate

D. 90% 5 yr survival

Colon Cancer Module


A. 20% 5 year survival rate

Mr. Jackson has stage IIIb colon cancer. The 5 year survival rate is about 60%.


Stage I — 93 percent Stage IIA — 85 percent Stage IIB — 72 percent Stage IIIA — 83 percent Stage IIIB — 64 percent Stage IIIC — 44 percent Stage IV — 8 percent

Colon Cancer Module


B. 40% 5 year survival rate

Mr. Jackson has stage IIIb colon cancer. The 5 year survival is about 60%.



Colon Cancer Module


C. 60% 5 year survival rate

Mr. Jackson has stage IIIb colon cancer. The 5 year survival is about 60% (see graph).


Question#10


Survival article

Colon Cancer Module


D. 90% 5 year survival rate

Mr. Jackson has stage IIIb colon cancer. The 5 year survival is about 60%.



Colon Cancer ModuleColon Cancer Module

Question #10: After recovering from his operation he presents for a consultation with a medical oncologist. What treatment is recommended for Stage III colon cancer?

A. Adjuvant Chemotherapy

B. Adjuvant Radiation

C. Observation and Surveillance

Colon Cancer Module


A. Adjuvant Chemotherapy

The 2005 colon cancer treatment guidelines from the National Comprehensive Cancer Network (NCCN) and American Cancer Society recommend adjuvant chemotherapy for all Stage III colon cancers.

Question#11

Return toQuestion #10 Systemic therapy article

Colon Cancer Module


B. Adjuvant Radiation

The 2005 colon cancer treatment guidelines from the National Comprehensive Cancer Network (NCCN) and American Cancer Society recommend adjuvant chemotherapy for all Stage III colon cancers. Unlike rectal cancers, radiation therapy is not a routine part of adjuvant treatment for colon cancer.


Colon Cancer Module


C. Observation and Surveillance

The 2005 colon cancer treatment guidelines from the National Comprehensive Cancer Network (NCCN) and American Cancer Society recommend adjuvant chemotherapy for all Stage III colon cancers. Observation and surveillance alone is NOT sufficient and results in poorer survival compared with patients who had received adjuvant chemotherapy.


Colon Cancer Module

Question # 11: What is the risk of Mr. Jackson developing a recurrence of his original cancer (local/regional or distant metastasis) over the next five years?

A. <10%

B. 15-20%

C. 40-60%

D. >80%

Colon Cancer Module


A. <10%


Approximate recurrence rate by stage

Stage I 10%Stage II 30%Stage III 50%

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B. 15-20%




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C. 40-60%

Question #12



Return toQuestion #11 Recurrence article

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D. >80%




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Question # 12: What is the risk of Mr. Jackson developing a second primary colon cancer over the next five years?

A. <1%

B. 1.5 -2.5%

C. 10-15%

D. >20%

Colon Cancer Module


A. <1%

The risk of developing a second primary colon cancer is noted to be higher than the risk of the general population. This risk is estimated to be approximately 0.3-0.5% per patient per year. Thus, at five years the cumulative risk of developing a second colon cancer is approximately 1.5-2.5%.


Colon Cancer Module


B. 1.5-2.5%

The risk of developing a second primary colon cancer is noted to be higher than the risk of the general population. This risk is estimated to be approximately 0.3-0.5% per patient per year. Thus, at five years the cumulative risk of developing a second colon cancer is approximately 1.5-2.5%. Moreover, if a patient lives 20yrs after his colon cancer diagnosis, the risk of developing a second colon cancer primary could be as high as 10%.


Question #13Second primary article

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C. 10-15%



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D. >20%



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Question # 13: Given these risks of recurrence and development of a second primary, what is the recommended follow up and cancer surveillance for Mr. Jackson over the next two years?

C. Office visit / CEA level every 3 months, colonoscopy once per year

B. Office visit / CEA level every 6 months, colonoscopy once per year

A. Office visit / CEA level every 6 months

Colon Cancer Module

A. Office visit / CEA every 6 months



According to the National Comprehensive Cancer Network (NCCN), follow up during the first 2 years after curative resection of stage III colon cancer should consist of:

• A history and physical every 3 months for 2 years

• CEA level every 3 months for 2 years

• Colonoscopy once per year for 2 years

• Consider abdominal CT scan every 6 months for 2 years if there is a high risk of recurrence

Colon Cancer Module

B. Office visit / CEA level every 6 months, colonoscopy once per year








Colon Cancer Module

C. Office visit / CEA level every 3 months, colonoscopy once per year








Continue caseNCCN guidelines

Colon Cancer Module

During a routine follow up visit 12 months after his operation, Mr. Jackson’s CEA level was noted to have risen from his previous value of 3 to 8 ng/ml. Recall that any value >5 ng/ml is considered abnormally elevated. You order a CT scan of the abdomen and this demonstrates a single 3 cm

Question #14

metastatic lesion (red arrow) in the left lobe of his liver. You also ordered a whole body PET scan which demonstrated a single area of positivity corresponding to the lesion in the left lobe. Mr. Jackson thus has evidence of a single site of colon cancerrecurrence in his left liver.

Personal Teaching File; James S. Tomlinson

Colon Cancer Module

Question # 14: You refer Mr. Jackson to a surgical oncologist who recommends hepatic resection of his metastatic colon cancer and states that this is the only potential curative therapy. Before Mr. Jackson undergoes such a radical procedure, he wants to know what are his chances of being cured if he undergoes the operation?

A. 0-5%

B. 5-10%

C. 15-25%

D. 50%

Colon Cancer Module

A. 0-5%

Surgical resection of colorectal liver metastasis (CLM) in selected patients with limited disease has become the standard of care in the past 20 years. A recently published study looked at over 600 patients who underwent resection of CLM with 10-year follow-up. The study found that in well-selected patients, the overall 10 year disease free survival is 15-25% after hepatic resection.


Back to Question #14

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B. 5-10%




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C.15-25%



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Back to Question #14 Hepatic resection article

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D.50%




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Mr. Jackson decides to go ahead with surgery and underwent a left lateral hepatic segmentectomy. He recovered well post operatively.

Continue Case

Colon Cancer Module

Left Lateral Hepatic Segmentectomy

Question#15


Colon Cancer Module

Question # 15: If Mr. Jackson initially had multiple sites of recurrence making surgical resection of his disease impossible, what would be his predicted median survival if he received current standard palliative chemotherapy (FOLFOX with Avastin)?

A. 0-5 months

B. 5-10 months

C. 15-20 months

D. 36-72 months

Colon Cancer Module

A. 0-5 months

In patients with advanced metastatic colon cancer, treatment with FOLFOX and Avastin has been shown to prolong median survival to approximately 15-20 months. By contrast, patients who do not receive any form of chemotherapy have a median survival of approxmately 6 months.



Colon Cancer Module

B. 5-10 months



Back toQuestion #15

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C. 15-20 months



Question #16

Back to Question #15 Systemic therapy article

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D. 36-72 months




Colon Cancer Module

Question #16: We have learned that most recurrences after being diagnosed with colon cancer occur within 2 years of diagnosis/resection. In accordance, follow up over the subsequent two years is considered intensive. If Mr. Jackson did not develop a recurrence within those two years, what would his cancer follow-up and surveillance plan be for the rest of his life?

A. Office visit / CEA level every 6 months until year 5 then yearly thereafter

C. Same level of intensive follow-up must be continued indefinitely

B. Office visit / CEA level every year, colonoscopy every 10 years

Colon Cancer Module

A. Office visit / CEA level every 6 months until year 5 then yearly thereafter

According to the National Comprehensive Cancer Network (NCCN) and American Cancer Society, follow up after the first 2 disease-free years after curative resection of stage III colon cancer should consist of:

• A history and physical every 6 months until year 5

• CEA level every 6 months through year 5

• Colonoscopy 2-3 years after year 2, and if no polyps, then every 5 years thereafter



End CaseColonoscopy surveillance article

Colon Cancer Module

B. Office visit / CEA level every year, colonoscopy every 10 years







Colon Cancer Module

C.Same level of intensive follow-up must be continued indefinitely







Colon Cancer Module

Inflammatory Bowel Disease Ulcerative Colitis & Crohn’s Colitis

BackIBD Photos

Patients with chronic colitis are at increased risk for developing colorectal cancer. The risk is 5% after 10 years, 20% after 20 years, and 40% after 25 years of duration of IBD. Risk of cancer may be reduced in patients who respond well to medical therapy. Surveillance with colonoscopy should begin 8-10 years after diagnosis of IBD, and repeated every 1-3 years with surveillance biopsies of the colon taken every 10 cm. Findings indicative of high grade dysplasia of the colonic mucosa should prompt consideration of surgical therapy (colectomy).

Colon Cancer Module

Inflammatory Bowel Disease Ulcerative Colitis & Crohn’s Colitis

www.GI-Pathology.net www.GI-Pathology.net

Ulcerative Colitis gross specimen

Crohn’s Colitis endoscopic view

Barium enema: colon with "lead-pipe" appearance in ulcerative colitis

www.learningradiology.com

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Colon Cancer Module

Lynch Syndrome (HNPCC)

HNPCC is an autosomal dominant syndrome caused by a germline mutation in one of the DNA mismatch repair (MMR) genes. It is associated with 2% - 3% of all colon cancer cases. The lifetime risk of a developing colon cancer can be as high as 70%. In recent report, median age of colon cancer diagnosis in patients with Lynch Syndrome (HNPCC) was 54 years in men and 70 years in women. This syndrome is also associated with tumors of other organs such as the uterus, ovaries, stomach, pancreas, ureters, kidneys, small bowel, biliary tract, and brain.

(Hereditary Non-Polyposis Colorectal Cancer)

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Colon Cancer Module

Familial Adenomatous Polyposis

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FAP is an autosomal dominant syndrome caused by germline mutation in the APC gene. It accounts for < 1% of all colon cancer cases. Approximately 50% of affected patients develop adenomatous polyps by age 15 and 95% by age 35. The average age at diagnosis of colon cancer is about 35-40 years. The lifetime risk of developing colon cancer in a patient with FAP approaches 100%.


Colon Cancer Module

Hamartomatous Polyposis Syndromes

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These are a group of rare hereditary syndromes associated with increased risk of developing colon cancer.

• Peutz Jeghers is an autosomal dominant syndrome notable for perioral pigmentation and histologically distinct gastrointestinal polyps (see picture). The lifetime risk for colon cancer is 40% and for breast cancer >50%.

• Juvenile polyposis is an autosomal dominant syndrome. The lifetime risk for colon cancer is 60% with a mean age of presentation at age 34 (see picture).

Colon Cancer Module

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Peutz Jeghers

www.GI-Pathology.nethttp://www.humpath.com/article.php3?id_article=2791

©1999 Division of Gastroenterology, Johns Hopkins Hospital

Colon Cancer Module

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Juvenile Polyposis

www.GI-Pathology.net www.humpath.com/juvenile-polyp

Colonic PolypsA polyp is a macroscopic protrusion of the colonic mucosa into the bowel lumen. Colonic polyps can be classified according to their malignant potential. Neoplastic polyps can become malignant while non-neoplastic polyps cannot. Within the group of neoplastic polyps, there are malignant polyps and benign but precancerous polyps that may evolve into carcinoma. The table below show examples of each category.

Neoplastic Non-neoplasticBenign Malignant Benign

Tubular adenoma Carcinoma in situ Hyperplastic polyps

Tubulovillous adenoma Invasive carcinoma Juvenile polyps

Villous adenoma Polypoid carcinoma Peutz-Jeghers polyps

Inflammatory polyps

Colon Cancer Module

Next

Colonic PolypsColonic adenomas are common in people over the age of 50. Most colon cancers arise in preexisting adenomatous polyps, but relatively few adenomas progress to cancer. Certain characteristics are associated with higher cancer risk. These include:

• Multiple adenomas • Size > 1.0 cm• Advanced histology (villous, tubulovillous, high grade dysplasia)• Proximal location of adenoma• Older age at diagnosis of adenoma(s)• Family history of colon cancer in a parent

Colon Cancer Module

Next

Colonic PolypsThe malignant potential of a polyp based on histology is: tubular < tubulovillous < villous. Cancer risk also rises with increasing size of the polyp. The table below shows the incidence of invasive carcinoma related to polyp histology and size based on analysis of 7000 polypectomy specimens.

Colon Cancer Module

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Tubular Tubulovillous Villous

0.5-0.9 0.3% 1.5% 2.5%

1.0-1.9 3.6% 6.4% 5.7%

2.0-2.9 6.5% 11.4% 17.0%

>3.0 11.0% 16.0% 20.0%

Size (cm)

Colonic polyps article Images from: www.endoatlas.com/atlas_co.html

Colon Cancer Module

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Hyperplastic Polyps

The epithelial cells at the base of the crypt (regenerative zone) have mildly enlarged, but uniform nuclei and brisk mitotic rate, feature which is normally present in reactive colonic mucosa

Endoscopic image of hyperplastic polyps


Colon Cancer Module

Tubular Adenoma

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The adenomatous polyp has a smooth outline and is composed of numerous architecturally simple crypts with mild irregularity in size and shape

Endoscopic image of a tubular adenoma

www.GI-Pathology.net www.endoatlas.com/atlas_co.html

Colon Cancer Module

Villous Adenoma

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Villous adenoma with glands that extend straight down from the surface to the base as fingerlike projections

Endoscopic image of a villous adenoma

www.endoatlas.com/atlas_co.htmlwww.GI-Pathology.net

Colon Cancer Module

Tubulovillous Adenoma

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Tubulovillous adenoma with 80% tubular histology and 20% villous histology

Endoscopic image of a tubulovillous adenoma

www.endoatlas.com/atlas_co.htmlwww.GI-Pathology.net

Colon Cancer Module

1. Minnesota Colon Cancer Control Study 46,551 participants; 50-80yrs of age18yr follow up demonstrated a 36% reduction in colon cancer mortality in

patients who underwent annual FOBT screening

2. United Kingdom-Nottingham FOBT Study 156,000 participants, 50-74yrs of age8 yr follow up demonstrated a 15% reduction in colon cancer mortality

in patients who underwent FOBT screening

3. Danish FOBT Study 62,000 participants, 45-74yrs of age, 10yr follow up demonstrated an 18% reduction in colon cancer

mortality in patients who underwent FOBT screening

Fecal Occult Blood Test (FOBT)Randomized Controlled Trials

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Colon Cancer Module


Carcinoembryonic antigen (CEA)CEA is a membrane-bound, surface protein expressed by fetal enterocytes and a variety of cancers, including colon adenocarcinoma. CEA level varies with tumor burden, grade, site, liver involvement, tobacco smoking, and many other factors. It is important to note that CEA levels should not be compared among different individuals. CEA is not used in colon cancer screening and diagnosis due to low sensitivity and specificity. In addition, CEA levels may also be elevated in other advanced adenocarcinomas and benign disorders. The utility of monitoring CEA levels is in the early detection of recurrent disease after curative resection of colon cancer, with an average lead time of 5 months. In addition, CEA levels can be used to follow response to treatment such as surgery, chemotherapy, or radiation therapy. A serum level above 5ng/ml is considered abnormal.

O'Connell, J. B. et al. J. Natl. Cancer Inst. 2004 96:1420-1425; doi:10.1093/jnci/djh275

Five-year survival by the American Joint Committee on Cancer sixth edition system stages I-IV

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Colon Cancer Module

Left Hemicolectomy

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hopkins-gi.nts.jhu.edu/pages/latin/templates/index.cfm?pg=disease4&organ=6&disease=36&lang_id=1

Colon Cancer Module

Right Hemicolectomy

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Colon Cancer Module

Abdominoperineal Resection

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Colon Cancer Module

Positron Emission Tomography in Colon Cancer

PET is a nuclear medicine imaging technique, often used in clinical oncology, for the whole body visualization of tumors and metastases. A glucose analog tracer such as [18F]-2-fluro-2 deoxy-D-glucose is injected into the circulation and is taken up by glucose-using cells. Fast growing malignant cells would take up more tracer and show up as areas of intensity (positivity). Studies have found PET to have 80-90% accuracy in the detection of recurrent and metastatic disease. PET can be helpful in preoperative staging and postoperative detection of recurrence/metastases.

BackSee Mr. Jackson’s

PET images

PET Scan

Liver

Coronal view

Mr. Jackson’s Tumor on CT and PET

Tumor

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Abdominal CT Scan



Colon Cancer Module

AJCC Staging System for Colorectal Cancer

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Primary Tumor (T)

TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ; intraepithelial or invasion

of lamina propria T1 Tumor invades submucosa T2

Tumor invades muscularis propria T3 Tumor invades through the muscularis propria into the subserosa, or into non-

peritonealized pericolic or perirectal tissues T4

Tumor directly invades other organs or structures, and/or perforates visceral peritoneum

Regional Lymph Nodes (N)

NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in 1 to 3 regional lymph nodes N2 Metastasis in 4 or more regional lymph

nodes

Distant Metastasis (M)

MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis

Stage Grouping

Stage T N M0 Tis N0 M0

I T1N0 M0

T2 N0 M0

IIA T3N0 M0

IIBT4 N0 M0

IIIA T1-T2

N1 M0

IIIB T3-T4 N1M0

IIIC Any T N2 M0 IV Any T

Any N M1

Colon Cancer Module

• Moderately differentiated adenocarcinoma of colonic origin

• Tumor is 4 cm x 3 cm x 3 cm. Tumor extends through through the muscularis propria into the subserosa

• Proximal and distal colonic margins are free of tumor. Closest margin is 10 cm.

• 2 out of 12 regional lymph nodes were positive for metastatic adenocarcinoma

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Pathology Report

Colon Cancer Module

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Gastroenterology 2003;124:544-560.4. NCCN colorectal treatment guidelines version IV 20055. Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: Is it clinically useful? Clinical Chemistry 2001;47(4):624-630.6. Wanebo HJ et.al. The use of preoperative carcinoembryonic antigen level as a prognostic indicator to complement pathological staging. NEJM

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25.10. Galandiuk S. et.al. Patterns of recurrence after curative resection of carcinoma of the colon and rectum. Surg Gynecol Obstet 1992;174(1):27-

32. 11. Russell AH, et al. Adenocarcinoma of the proximal colon: sites of initial dissemination and patterns of recurrence following surgery alone. Cancer

1984;53:360-7.12. Cali RL, et al. Cumulative incidence of metachronous colorectal cancer. Dis Colon Rectum 1993;36:388-93. 13. Jacobson BC, et al. Surveillance after colorectal cancer resection. UpToDate 2007.14. Anthony T. Colorectal cancer follow-up in 2005. Surg Oncol Clin N Am 2006;15:175-193.15. Blumgart LH and Fong Y. Surgical options in the treatment of hepatic metastasis from colorectal cancer. Curr Probl Surg 1995;32(5):333-421.16. Simmonds, PC. Palliative chemotherapy for advanced colorectal cancer: Systematic review and meta-analysis. Colorectal Cancer Collaborative

Group. BMJ 2000;321:531-535.17. Lawrence SP and Ahnen DJ. Epidemiology and risk factors for colorectal cancer. UpToDate 2007. 18. Mandel JS, et. al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl

J Med 1993;328:1365-1371.19. Hardcastle JD, et. al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996;348(9040):1472-7.20. Kronborg O, et al. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996;348(9040):1467-71.21. Strate LL and Syngal S. Hereditary colorectal cancer syndromes. Cancer Causes and Control 2005;16:201-213.22. Kim DH, et. al. CT colonography versus colonoscopy for the detection of advanced neoplasia. New England Journal of Medicine 2007;357:1403-

12.23. Meyerhardt JA and Mayer RJ. Systemic therapy for colorectal cancer. New England Journal of Medicine 2005;352:476-87.24. Tomlinson JT, et. al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol 2007;25:4575-4580.25. Shinya H and Wolff WI. Morphology, anatomic distribution, and cancer potential of colonic polyps. Ann Surg 1979;1990:675.26. Loeve F, et. al. Colorectal cancer risk after colonoscopic polypectomy: a population-based study and literature search. Eur J Cancer

2005;41(3):416-422.27. Green RJ, et. al. Surveillance for second primary colorectal cancer after adjuvant chemotherapy: an analysis of intergroup 0089. Annals of

Internal Medicine 2002;136:261-269.28. Manfredi S. Incidence and patterns of recurrence after resection for cure of colonic cancer in a well define population. British J Surgery

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society task force on colorectal cancer. CA Cancer J Clin 2006;56:160-167.

References

cancer colon cancer epidemiology, treatment, and survival david geffen ucla school of medicine 2007...

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