Colon Cancer Screening

Ryan BurrisJames FryeMelvie Kim

Nicholas LeeJennifer MahHoa Nguyen

Epidemiology

• Colorectal cancer is the third most common cancer in the US (70% arise in the colon)

• Each year there are approximately 133,000 new cases diagnosed and approximately 50,000 deaths (8% of all cancer deaths)

• Worldwide highest incidence in Australia, New Zealand, Europe and North America. Lowest incidence in Africa and South Central Asia

• Incidence in US has declined 2-3% per year over the last 15 years (increased screening and polyp removal)

Risk Factors• Age (incidence increases between 40-50 yo)• Men (incidence 25% higher )• African American ( incidence 20% higher than whites)• Family History (first degree relatives, age of onset)• Hereditary CRC Syndromes (FAP, HNPCC-5% of call CRC cases)• Personal History of Large (>1 cm) adenomatous polyps w/ villous or

tubulovillous histology or high grade dysplasia • Inflammatory Bowel Disease (UC, fewer data to suggest Crohn’s disease)• Abdominal Radiation • Acromegaly • Diabetes (? Insulin is growth factor for colonic mucosal cells)• Renal Transplant on Immunosuppression • Low Socioeconomic Status• Unhealthy Diet (red and processed meats {BACON}, high temperature cooking)• Smoking and Alcohol • Obesity

Protective Factors

• Regular Physical Activity• Fruits and Vegetables• Fiber• ASA and NSAIDs (?increased apoptosis and impairment

of tumor cell growth by inhibition of COX-2)• Post Menopausal Hormonal Therapy• ?Folic Acid, Folate, Vitamin B6, Dietary/Supplemental

Calcium, Vitamin D, Magnesium, Garlic, Omega 3 Fatty Acids, Statins

Pathogenesis

• Involves a sequence of events resulting in the transformation of adenomatous polyps to cancer

• Early mutations in adenomatous polyposis coli gene (APC) lead to initial hyperproliferative state

• Accumulation of additional mutations and abnormal DNA methylation further drives the malignant transformation from adenoma to carcinoma

Pathogenesis

• CRC spreads through the lymphatics, hematogenously or by contiguous and transperitoneal routes.

• The TNM staging system is used for CRC• Metastasis is often to regional lymph nodes,

liver, lungs and peritoneum

Familial Adenomatous Polyposis

• Characterized by numerous colonic adenomas appearing during childhood with significant malignant potential (90% will develop cancer by 45 yo)

• Symptoms occur at approximately 16 yo• Secondary to germline mutations in the

adenomatous polyposis coli (APC) gene on chromosome 5

Hereditary Non-Polyposis Colorectal Cancer

• Also known as Lynch Syndrome• More common than FAP• Autosomal Dominant • Caused by defects in the mismatch repair genes

(hMLH1, hMSH2, hMSH6, PMS2) • Characterized by early age of onset and right sided

tumors (70% proximal to splenic flexure)• Extracolonic cancers common (endometrial, ovary,

stomach, small bowel, hepatobiliary, brain, renal, breast, prostate)

Clinical Presentation

• Patients often present in three ways– Suspicious symptoms and/or signs– Asymptomatic individuals discovered by routine

screening (over 30% of all CRCs)– Emergency admission with intestinal obstruction,

peritonitis, or rarely an acute GI bleed• Most are diagnosed after symptom onset

Clinical Presentation• Signs and Symptoms

– Hematochezia (more commonly left sided tumors)– Melena (more commonly right sided tumors)– Iron Deficiency Anemia (more commonly right sided tumors)– Abdominal Pain (tumors at all sites due to obstruction, peritoneal spread, perforation)– Change in Bowel Habits (more commonly left sided tumors)– Nausea/Vomiting (obstructive signs)– Abdominal Distention– Tenesmus (Rectal CA)– Rectal Pain (Rectal CA)

• Atypical Presentations– Malignant fistula formation (bladder, small bowel)– Fever of Unknown Origin– Abscesses – Streptococcus bovis bacteremia

Screening Modalities

• Stool-Based TestDetection of hemoglobin in stool– Guaiac-based Fecal Occult Blood Test (gFOBT) (chemical

guaiac)– Sensitive FOBT (chemical guaiac)– Fecal Immunochemical Test (antibodies)

Limitations of Stool-Based Test: Not good for polyp detection and many false-positivesAdvantages: Low cost, risk and complexity of performing test

Screening Modalities

• Colon Imaging and Direct Visualization– Double-contrast barium enema

• Advantages: Relatively safe and can view entire colon• Limitations: Abnormal results still need colonoscopy, false-

positives from retained stool, air, and other mucosal irregularities

– Sigmoidoscopy• Advantages: Bowel prep less onerous than for colonoscopy

and can be performed without sedation• Limitations: Screens up to splenic flexure only, can cause

perforation, abnormal tests requires follow up colonoscopy

Screening Modalities

– CT Colonography• Advantages: No sedation required• Limitations: Aggressive bowel prep required, abnormal

results require follow up colonoscopy– Capsule Endoscopy• Advantages: Less invasive• Limitations: Not an option for initial test, only for

incomplete colonoscopy. Requires more rigorous bowel prep, no intervention thus requires follow up colonoscopy for abnormal results

Screening Modalities

– Colonoscopy**Preferred option by American College of Gastroenterology• Advantages: intervention can be completed during

same procedure, can detect proximal lesions better than sigmoidoscopy• Limitations: risk of perforation or bleeding (1 in 1000),

expensive, conscious sedation, bowel prep

Screening Modalities

• Investigational– Chromoendoscopy, magnification endoscopy,

narrow band imaging optical colonoscopy– Serum markers• Septin 9 hypermethylation• Seven gene test

SCREENING

Two major United States guidelines were released in 2008

1) Multi-Society Task Force 2) the US Preventive Services Task Force (USPSTF)

Two major United States guidelines were released in 2008

Multi-Society Task Force -prefers tests that can prevent cancer over those that mainly offer early

detection of cancers.-more inclusive in the tests it recommended

(the best test is the one patients will take)

the US Preventive Services Task Force

Two major United States guidelines were released in 2008

Multi-Society Task Force -prefers tests that can prevent cancer over those that mainly offer early

detection of cancers.-more inclusive in the tests it recommended

(the best test is the one patients will take)

the US Preventive Services Task Force -required a higher level of evidence for including a test.-more explicit about the age to stop screening.

Whether to recommend screening >70 years of age should depend upon the health status, anticipated life expectancy, risk for colorectal cancer, and personal values

Whether to recommend screening >70 years of age should depend upon the health status, anticipated life expectancy, risk for colorectal cancer, and personal values

Patients with a life expectancy less than ten years (some would say five) would not be expected to benefit from colorectal screening, since studies indicate benefit from screening starts to accrue after about five years.

Whether to recommend screening >70 years of age should depend upon the health status, anticipated life expectancy, risk for colorectal cancer, and personal values

Patients with a life expectancy less than ten years (some would say five) would not be expected to benefit from colorectal screening, since studies indicate benefit from screening starts to accrue after about five years.

Colonoscopy carries increased risk in older adults, with significant

complications occurring in 0.3 percent of 600 veterans aged 70 to 75 undergoing colonoscopy screening

There are no randomized, controlled trials of screening in people with a family history of colorectal cancer. Screening recommendations are mostly based on expert opinion

The American College of Gastroenterology (ACG) issued guidelines in 2008

There are no randomized, controlled trials of screening in people with a family history of colorectal cancer. Screening recommendations are mostly based on expert opinion

The American College of Gastroenterology (ACG) issued guidelines in 2008

Screen with colonoscopy.

There are no randomized, controlled trials of screening in people with a family history of colorectal cancer. Screening recommendations are mostly based on expert opinion

The American College of Gastroenterology (ACG) issued guidelines in 2008

Screen with colonoscopy.

If a single first-degree relative was diagnosed at age 60 years or older with CRC or an advanced adenoma (≥1 cm, or high-grade dysplasia, or villous elements), screening with colonoscopy is recommended every 10 years beginning at age 50, consistent with one option for average risk screening

There are no randomized, controlled trials of screening in people with a family history of colorectal cancer. Screening recommendations are mostly based on expert opinion

The American College of Gastroenterology (ACG) issued guidelines in 2008

Screen with colonoscopy.

If a single first-degree relative was diagnosed at age 60 years or older with CRC or an advanced adenoma (≥1 cm, or high-grade dysplasia, or villous elements), screening with colonoscopy is recommended every 10 years beginning at age 50

If a single first-degree relative was diagnosed before 60 years with CRC or an advanced adenoma, or two or more first-degree relatives had colorectal cancer or advanced adenomas at any age, screening with colonoscopy is recommended at age 40 or 10 years before the youngest relative's diagnosis, to be repeated every five years.

Classic FAP If genetic testing cannot be done or is uninformative:Screening gene carriers or at-risk family members with flexible sigmoidoscopy or colonoscopy every 12 months starting around age 10 to 12 years and continuing until age 35 to 40 years if negative. Once colonic polyposis is established, a full colonoscopy should be performed to evaluate the extent of the colonic polyposis. Colectomy near the time of initial diagnosis in patients with profuse polyposis, multiple large (>1 cm) adenomas, or adenomas with villous histology and/or high-grade dysplasia. Patients with sparse, small (<5 mm) adenomas can usually be followed endoscopically with surgery scheduled to accommodate school and work schedules. Patients who have undergone total proctocolectomy require regular surveillance of the ileal pouch.

Lynch syndrome CRC screening with colonoscopy

-every 1to 2years beginning at age 20-25 years,-or two to five years prior to the earliest age of CRC diagnosis in the family

Lynch syndrome CRC screening with colonoscopy

-every 1to 2years beginning at age 20-25 years,-or two to five years prior to the earliest age of CRC diagnosis in the family

(whichever comes first)

Surveillance

Surveillance

Low-risk adenomas – If only one or two small (≤10 mm) tubular adenomas are found on baseline colonoscopy, the first surveillance colonoscopy should be performed in 5 to 10 years

Surveillance

Low-risk adenomas – If only one or two small (≤10 mm) tubular adenomas are found on baseline colonoscopy, the first surveillance colonoscopy should be performed in 5 to 10 years

Individuals with advanced adenomas (≥10 mm, villous histology or high-grade dysplasia)or between 3 and 10 adenomas on their first surveillance colonoscopy should undergo their next surveillance colonoscopy in three years

Surveillance

Low-risk adenomas – If only one or two small (≤10 mm) tubular adenomas are found on baseline colonoscopy, the first surveillance colonoscopy should be performed in 5 to 10 years

Individuals with advanced adenomas (≥10 mm, villous histology or high-grade dysplasia)or between 3 and 10 adenomas on their first surveillance colonoscopy should undergo their next surveillance colonoscopy in three years

patients with more than 10 adenomas should be evaluated for a hereditary colorectal cancer syndrome and have surveillance colonoscopy in less than three years

Colorectal cancer surveillance in IBD• Necessary. • Lack of evidence on the interval and location• Grade 1B/Strong recs: colectomy for high grade dysplasia

• Grade 2B/Weak recs: • colectomy for those with low-grade dysplasia • UC past splenic flexure or Crohn colitis, first colonoscopy 8

yrs after disease onset then annually • Grade 2C/Very weak recs:

– left-sided UC, begin colonoscopy after 12 years of disease; then annually

CRC MKSAP

Question 1

A 57-year-old woman is evaluated after a recent screening colonoscopy. The colonoscopy disclosed a 12-mm polyp in the ascending colon, which was removed. No other lesions were noted. On pathology, the lesion was found to be a sessile serrated polyp.

Physical examination findings are unremarkable.

Which of the following is the most appropriate time to repeat colonoscopy?

A. 1 yearB. 3 yearsC. 5 yearsD. 10 years

B. 3 years

• Hyperplastic polyps– No malignant potential

• Sessile serrated polyps– Precursor of 15% of sporadic colorectal cancers– <10 mm repeat colonoscopy in 5 years– ≥ 10mm repeat colonoscopy in 3 years

• Serrated adenomas

Key Point

For patients with large (≥10mm) or dysplastic sessile serrated polyps or traditional serrated adenomas, the recommended postpolypectomy surveillance colonoscopy interval is 3 years.

Question 2

A 65-year-old man is evaluated after a recent colonoscopy, which disclosed a 2.5-cm pedunculated polyp in the sigmoid colon. The polyp was removed in its entirety in one piece. Biopsy results showed a well-differentiated adenocarcinoma confined to the submucosa without evidence of lymphovascular involvement and a 1-mm margin. There is no family history of colorectal cancer.

Physical examination findings are unremarkable.

Which of the following is the most appropriate management?

A. Colon resectionB. CT scan of the abdomen and pelvisC. Radiation therapyD. Repeat colonoscopy in 3 months

D. Repeat colonoscopy in 3 months

• Invasive adenocarcinoma in a pedunculated polyp is adequately treated by endoscopic en bloc polypectomy alone if:– Confined to the submucosa– Not poorly differeniated– No lymphatic or vascular invasion– No involved margins

D. Repeat colonoscopy in 3 months

• If adverse histologic features are noted, there is increased risk of lymph node involvement and surgical resection is required

• Consider surgery if the lesion is removed piecemeal

Key Point

National recommendations for postpolypectomy surveillance intervals are as short as 3 to 6 months in patients with large (>2cm) adenomas with invasive cancer and favorable prognostic features.

Question 3

A 62-year-old man is evaluated after a recent screening colonoscopy. The colonoscopy disclosed a 3-mm sigmoid polyp and an 8-mm hepatic flexure polyp, both of which were removed. On pathology, the sigmoid polyp is noted to be a hyperplastic polyp, and the hepatic flexure polyp is found to be a tubulovillous adenoma with high-grade dysplasia.

Physical examination findings are unremarkable.

Which of the following is the most appropriate time to repeat colonoscopy?

A. 3 to 6 monthsB. 1 yearC. 3 yearsD. 5 years

C. 3 years

• Adenomas = increased risk for colon cancer• Low risk next colonoscopy in 5 years– 1 or 2 adenomas smaller than 10mm

• High risk next colonoscopy in 3 years– Adenoma 10mm or larger– 3 to 10 adenomas– Adenoma with villous component (tubulovillous or

villous adenoma)– Adenoma with high-grade dysplasia

Question 4

A 72-year-old man is evaluated during a routine examination. He underwent a sigmoid colectomy and adjuvant chemotherapy 4 years ago for stage III adenocarcinoma of the colon. Results of the colonoscopies performed 1 year postoperatively and last year were normal.

On physical examination, he appears healthy and has no evidence of recurrent disease.

Which of the following is the most appropriate time to repeat colonoscopy?

A. 1 yearB. 3 yearsC. 5 yearsD. 10 years

C. 5 years

• Screening recommendations for patients with a history of colorectal cancer consists of follow-up colonoscopy at 1 year and 3 years after curative surgical resection

• If results of these colonoscopies are normal, the surveillance interval can be extended to 5 years

Question 5

A 38-year-old woman is evaluated in follow-up after recent surgery for endometrial cancer. Her family history is significant for colon cancer in her sister (diagnosed at age 45 years) and her mother (diagnosed at age 65 years). Her maternal grandfather was diagnosed with rectal cancer at age 47 years. The patient has never had a colon cancer screening with colonoscopy.

Which of the following is the most appropriate time to start colon cancer screening with colonoscopy?

A. NowB. Age 40 yearsC. Age 47 yearsD. Age 50 years

A. Now

• Hereditary nonpolyposis colorectal cancer• Amsterdam II criteria– 3 or more relatives with HNPCC-associated cancer• Colorectal, endometrial, ovarian, urothelial, gastric,

brain, small bowel, hepatobiliary, skin– 2 successive generations of relatives affected– 1 affected relative a first-degree relative or 2 other

affected relatives– 1 cancer diagnosed before age 50 years

A. Now

• Surveillance colonoscopy is indicated for patients who– Meet the clinical criteria for HNPCC– Have Lynch syndrome (presence of germline

genetic mutation)– Are at risk for Lynch syndrome and have not had

genetic testing

A. Now

• The recommended surveillance interval for colonoscopy screening in patients who have or at risk for Lynch syndrome is– Every 1 to 2 years beginning at age 25 years, or– 2 to 5 years earlier than the youngest age at

diagnosis of colorectal cancer if the affected relative was younger than 25 years old

References

• UpToDate• Medscape