Colorectal Cancer

Epidemiology and risk factors

• 3rd most common cancer in US men and women; 2nd leading cause of oncer death overall

• Age: rare before 40. with 90% of cases occurring after age 50

• Genetics: up to 25% of patients have © FHx: risk depends on number of 1st-degree relatives (with CRC or polyp) and age at dx; -5% have an identifiable germlinc mutation Familial adenomatous polyposis (FAP): mutabon of APC tumor suppressor 1000s of polyps at young age - • 100% lifetime risk; T risk of thyroid, stomach. SI cancers Hereditary nonpolyposis colorectal cancer (HNPCC): mutations in DNA mismatch repair genes T tumor progression -» 80% lifetime risk; predom. right-sided tumors; T risk of endometrial, ovarian, stomach, small bowel cancers

• Inflammatory bowel disease:? risk with T extent and duration of disease

• 1 risk of adenomas w ASA & NSAIDs. Ind. COX-2 (NQM 2006355873.885). but T bleeding and T CV events w COX-2; 1 COX-2-exprossing colorectal cancer after prolonged ASA (NEJM 2007;3S6:2131;Umcrt 2007:3691603). currently not recommended (Annak 2007.146 361) Pathology

• Adenoma carcinoma sequence reflects accumulation of multiple genetic mutations t risk of malignancy with large (>2.5 cm), villous, sessile adenomatous polyps I

• 50% of colon tumors are proximal to splenic flexure Clinical manifestations

• Distal colon: A bowel habits, obstruction, colicky abdominal pain, hematochezia

• Proximal colon: Iron defic. anemia, dull vague abd pain; obstruction atypical due to larger lumen, liquid stool, and polypoid tumors (vs. annular distal tumors)

• Metastases: nodes, liver, lung, peritoneum — RUQ tenderness, ascites, supraclavicular LN

• Associated with Streptococcus bovis bacteremia and Clostridium septkum sepsis

Screening (NE^M 2002:346:40)

• Average risk & age -50: q5y flex sig + q1y FOBT or q10y colonoscopy

• t risk earlier (age 40 if © FHx) and or more frequent screening based on risk factor(s)

• Endoscopy: colonoscopy test of choice as examines entire colon; 2 of Pts w advanced proximal neoplasms have no distal polyps (N£/m 2000.343 162.169)

flexible sigmoidoscopy vs. 0 endo. shown to i distal CRC mortality (nejm 1991326:653)

• Fecal occult blood test (FOBT): i mortality (nejm 1993328 1365 & 2000.343:1603).

6-sample (3 cards) home testing much more Se (24% vs. 5%) than single physician DRE FOBT at identifying advanced neoplasia (Amwfe 2005:142.81)

• Fecal DNA: T Se. - Sp c w FOBT. but less Se than colonoscopy {nejm 2004:351 2704)

• Imaging: air-contrast barium enema (ACBE) and CT colonography are both less Se than colonoscopy (tone« 2005:365:305). especially for lesions <1 cm Staging

• Colonoscopy • biopsy polypectomy

• Abdomen pelvis CT (but inaccurate for assessing depth of invasion & malignant LN)

• Intraoperative staging is essential for evaluating extracolonic spread

• Tumor markers: baseline CEA in Pt with known CRC has prognostic significance and is useful to follow response to therapy and detect recurrence; not a screening tool

Treatment Based on TNM and Modified Dukes Staging of Colorectal Cancer

TNM

Dukes

Criteria

S-y surv.

Treatment

A

Into submucosa

95%

Surgery alone

B1

Into muscularis

90%

IIA

B2

Into serosa

80%

Surgery; no established role for

IIB

B2

Direct invasion

70%

adjuvant chemotherapy*

IIIA/B

c

© LNs

65%

Surgery - chemotherapy*

IIIC

c

>4 © LNs

35%

FOIFOX

IV

D

Distant metastases

1st line: FOLFOX or irinotecan (FOLFIRI). bevaciiumab 2nd line: irinotecan - cetuximab t palliative surgery1

•Consider adjuvant chemo for high-risk stage II (obstruct perf., adherence to ad|. structures, rnadeq. nodal sampling, lymphovasc. evasion, poorly differentiated) For stage II or III rectal cancer combined chemoradiabon surgery chemo.* Surgical resection of isolated liver or lung metastases associated with 30% 5-y survival (NEjM 2004350.2343 & 2004 351:337 & 2005:352:476 & 2006355 1114)

•Consider adjuvant chemo for high-risk stage II (obstruct perf., adherence to ad|. structures, rnadeq. nodal sampling, lymphovasc. evasion, poorly differentiated) For stage II or III rectal cancer combined chemoradiabon surgery chemo.* Surgical resection of isolated liver or lung metastases associated with 30% 5-y survival (NEjM 2004350.2343 & 2004 351:337 & 2005:352:476 & 2006355 1114)

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