I. Genetic factors and hereditary syndromes involving elevated colorectal cancer risk

  1. Hereditary nonpolyposis colorectal cancer (HNPCC) aka Lynch syndrome
    1. Autosomal dominant; high penetrance
    2. Causes 75-80% of hereditary colorectal Ca
    3. Caused by a mutation in a DNA repair gene, resulting in shortened progression from benign polyp to malignancy (18-24 months as opposed to 10-12y normally)
    4. Causes predominantly right-sided colorectal Ca with high-grade histology
    5. Studies of tumor DNA show microsatellite instability in > 90% of cases, compared with 10% of sporadic colorectal cancers
    6. Associated with malignancy in other organs, including endometrial, gastric, small intestine, ovarian, renal pelvis, ureter, and hepatobiliary tree.
    7. In addition to those who have genetic tests confirming HNPCC, per an "International Collaborative Group" convened on the topic, patients who meet all of the following ("Amsterdam II") criteria should be managed as if they have HNPCC (> 50% of such patients have abnormal HNPCC genetic tests):
      1. 3 or more relatives with an HNPCC-related Ca, of whom one is a first-degree relative of the other two
      2. Involvement of at least 2 generations
      3. At least one case diagnosed prior to age 50y
      4. Exclusion of FAP syndromes
    8. Screening recommendations for patients with HNPCC
      1. Start at age 20-25 or 10y younger than age of earliest colorectal cancer diagnosis, whichever is earlier
      2. Colonoscopy Q1-2y until age 40y, then annually
      3. If adenoma or colon Ca found, total consider colectomy with ileo-rectal anastomosis
  2. Familial adenomatous polyposis (FAP)
    1. Autosomal dominant
    2. Patients have hundreds to thousands of polyps in all parts of colon
    3. Mean age of initial polyp development is 15y, but progression from adenoma to malignancy is 15-20y
    4. Also associated with adenomata of stomach and duodenum as well as periampullary carcinoma, thyroid carcinoma, hepatoblastoma, desmoid tumors, osteomata, and tumors of adrenal gland and brain.
    5. Caused by a mutation in the adenomatous polyposis coli (APC) gene which is identifiable in 80% of patients with FAP
    6. Most patients undergo total colectomy by age 20y
    7. Screening
      1. Usually by sigmoidoscopy since rectal polyps are very common in these patients
      2. Q1-2y starting at age 10-12y; If no polyp found by age 40, can increase screening interval to Q3-5y
      3. If a polyp is found, switch to annual colonoscopy
      4. Consider upper endoscopy at time of planned colectomy and again 5y later
    8. Consider offering genetic testing to family members > 10yo of patients with FAP and even if test negative, consider signoidoscopy Q7-10y until age 40 then colonoscopy Q5y
  3. Attenuated familial adenomatous polyposis (attenuated FAP) aka attenuated adenomatous polyposis coli (AAPC)
    1. Autosomal dominant
    2. Caused by a mutation in the adenomatous polyposis coli (APC) gene (at a different site than FAP)
    3. Rarer than FAP
    4. Generally have < 100 polyps and often limited to right side of colon
    5. Lifetime risk of colorectal Ca is > 80% with mean age at diagnosis 54y
    6. Also associated with risk for upper GI adenomata and extra-GI tumors
    7. Screening of patients with family history of AAPC
      1. Colonoscopy starting in early 20's Q2y until polyp identified, then Q1y
      2. Total colectomy is considered if polyps are found
  4. MUTYH-associated polyposis (MAP)
    1. Autosomal recessive
    2. Clinical manifestations can be similar to FAP or AFAP (mostly right-sided adenomata)
    3. Mean age of colorectal Ca diagnosis is 45y
    4. Similar upper GI manifestations as FAP
    5. Also, increased risk for breast, bladder, and skin Ca
    6. Screening: Colonoscopy Q2y starting 18-20yo with upper endoscopy starting 25-30yo
  5. Gardner's syndrome
    1. Rare
    2. Also involves osteomas and fibromas
  6. Turcot's syndrome
    1. Rare
    2. Also involves brain tumors
  7. Peutz-Jeghers syndrome
    1. Rare
    2. Also involves bowel hamartomas
  8. Cowden's syndrome
    1. Rare
    2. Also involves breast and thyroid carcinomata

II. Precursors to colorectal adenocarcinoma

  1. Adenomatous polyps
  1. Adenomatous polyps are found in 5% of all barium enemas
  1. 50% are in recto-sigmoid
  2. 50% are multiple
  1. Morphological classification
  1. Tubular (adenomatous)--7% become malignant
  2. Tubulovillous (villoglandular)--20% become malignant
  3. Villous--33% become malignant
  4. Tubular & tubulovillous are us. pedunculated; villous us. sessile
  1. Do all distal adenomatous polyps seen on sigmoidoscopy need to be f/u'd with colonoscopy?
    1. 401 pts > 50yo with negative fecal occult blood tests and no risk factors for colon Ca who had adenomatous polyps on flex sig. were studied. 301 subsequently underwent colonoscopy. The likelihood of colonoscopy revealing an "advanced" proximal polyp (tubulovillous, villous, or cancerous), was 6% in pts who on sigmoidoscopy had had either multiple small (1-5mm) tubular adenomas, any tubular adenoma 6-10mm in diameter, or "advanced" polyps, and 0% (95% CI 0-4%) in pts who had had a single small (1-5mm) tubular adenoma at sigmoidoscopy (Ann. Int. Med 129:273, 1998--JW)
  1. Prevention of adenomata
  1. Calcium
    1. 930 pts with recently removed adenomatous polyps randomized to CaCO3 3g/d (1.2g elemental Ca) vs. placebo. Followup colonoscopy at 4y showed RR of adenoma of 0.85 (sig.) (NEJM 340:101, 1999--JW)
      1. In a follow-up study in 597 participants in the original trial who underwent at least one additional colonoscopy during mean 7y post-trial f/u, the pts originally randomized to ca had sig. lower incidence of new adenomata (32% vs. 43%) for colonoscopies done during the first 5y after the trial ended but beyond that time period there was no sig. diff. (J. Nat. Ca. Inst. 99:129, 2007--JW)
    2. pts with recent dx of colorectal polyps randomized to CaCO3 1.2g/d vs. placebo; there was no sig. diff. at 4y in overall incidence of polyp recurrence, though incidence of advanced neoplasms (tubulovillous or villous adenomata, CIS, or invasive Ca) was sig. lower in Ca group (10% vs. 15%) (J. Nat. Ca. Inst. 96:921, 2004--AFP)
    3. In a study in 36,282 postmenopausal women 50-79yo randomized (as part of the Women's Health Initiative) to (calcium carbonate 500mg + vitamin D3 200IU) BID vs. placebo, over mean 7y f/u, there was no sig. diff, in incidence of invasive colorectal Ca (NEJM 354:684, 2006--JW)
  2. Aspirin
    1. In a case-control study of 379 pts undergoing colonoscopy, regular use of ASA or NSAIDs was ass'd with RR 0.56 for having an adenoma on colonoscopy, after adjustment for a variety of confounders (sig.; Gastroent. 114:441, 1998--JW)
    2. 635 pts with prior colorectal Ca randomized to ASA 325 mg PO QD vs. placebo.  Over avg. 31mo f/u (during which time most had 1-2 colonoscopies), incidence of recurrent adenomata was sig. lower in ASA recipients (17% vs. 27%) (NEJM 348:883, 2003--JW)
    3. 1121 pts with prior adenomatous colonic polyp randomized to ASA 325mg/d, ASA 81mg/d, or placebo.  Over mean 33mo f/u, recurrent adenomata dx'd in 45%, 38%, and 47%, respectively (only diff. between 81mg/d and placebo groups was sig.). (NEJM 348:891, 2003--JW)
    4. 272 pts with h/o adenomatous colorectal polyps randomized to lysine acetylsalicylate 160mg/d or 300mg/d vs. placebo.  Prevalence of adenomatous polyps on repeat colonoscopy at 1y was not sig. diff. between the two groups. ("APACC" Trial; Gastroent. 125:328, 2003--AFP)
    5. In a study of data from the Nurses' Health Study (a large prospective study of American women), ASA use was ass'd with lower risk of colon adenomata among those who underwent colonoscopy or sigmoidoscopy; there was an apparent dose-response relationship, though no relationship was seen between duration of use and risk of adenomata (Ann. Int. Med. 140;224, 2004--AFP)
    6. In a meta-analysis of four randomized trials comparing ASA 81-325mg/d vs. placebo in pts with recently-resected colorectal adenomata or Ca, ASA recipients had sig. lower risk for recurrent adenomata (RR 0.83) (J. Nat. Ca Inst. 101:256, 2009-JW)
  1. Hyperplastic polyps
    1. Tend to occur on the right side of the colon
    2. Traditionally thought to have no malignant potential or association with colorectal malignancy, but that may or may not be true
      1. Some hyperplastic polyps contain microsatellite instability, an abnormality in non-protein-coding portions of DNA also found in some colorectal cancers (J. Nat. Ca. Inst. 93:1307, 2001--JW)
      2. In a cross-sectional study in 2,357 asymptomatic pts undergoing screening colonoscopy, prevalence for proximal neoplasia  was not sig. diff. in pts with distal hyperplastic polyps (but no distal adenomata) vs. those with no distal hyperplastic polyps or adenomata (12% and 9%, respectively) (Am. J. Med. 118:1113, 2005--JW)

III. Colorectal polyps in children

  1. 90% are hyperplastic; around 80% are solitary and around 80% are in recto-sigmoid area
  2. Hyperplastic polyps in children are not associated with an elevated risk of colorectal cancer
  3. Generally present with painless rectal bleeding (most common cause of rectal bleeding in children 2-10yo)
  4. Colorectal adenomata in children
    1. Malignant transformation is possible
    2. Highest-risk are villous in histology, > 1cm in size, or > 3 in number
    3. Juvenile Polyposis Syndrome
      1. Defined by number of GI polyps (5 of more)
      2. Characteristic "hamartomatous" histology (expanded lamina propria, diffuse inflammatory cell infiltration, dilated mucoid cystic glands)
      3. Strong familial component-Consider screening family members with upper & lower endoscopy from age 15yo

IV. Screening for colorectal cancer

U.S. Multisociety Task Force on Colorectal Cancer (an expert panel convened by AHCPR) recommends the following (Gastroenterology 124:544, 2003):

  • "Average risk": Screen all starting @ age 50 w/FOBT Q1y, flex sig Q5y, colonoscopy Q10y, or double-contrast barium enema Q5y.
  • If first-degree relative (parent, sib, child) w/colorectal neoplasia (adenoma or Ca) dx'd @ < 60yo, or > 1 first-degree relatives w/colorectal neoplasia @ any age--Colonoscopy @ 40yo or 10y before youngest dx in the family, whichever comes first.
  • If 1 first-degree relative w/colorectal neoplasia at 60yo or older, do "average risk screening" but start @ 40yo.
  • If h/o adenomatous polyp, repeat colonoscopy in 3y if had 3 or more or any were "advanced", otherwise 5y
  • If h/o colorectal Ca, repeat colonoscopy in 3y then Q5y

ACG 2008:
  • Average risk: Colonoscopy Q10y starting @ age 50y (45y in African-Americans)
  • High risk: If family h/o (colorectal cancer or advanced adenoma) in > 1 first-degree relative or (one first-degree relative diagnosed age < 60yo) then colonoscopy Q5y starting at the earlier of (age 40 or 10y younger than earliest age of diagnosis in first-degree relative)

  • USPSTF recomments initiating screening at age 50 and continuing through age 75
  1. Fecal Occult Blood Testing ("Hemoccults")--Studies showing reduced mortality
  1. Annual FOBT was ass'd with reduced mortality from colorectal Ca in tested subjects by 33% at 13y c/w controls in a randomized trial (NEJM 328:1365, 1993--JW); every 2y screening was not as effective (J. Natl. Ca. Inst. 3:91, 1999--JW)
  1. A Danish study randomized 62,000 people 45-75yo to every-other year screening with Hemoccult II with dietary resrictions, without rehydration for 10y vs. no screening.  If positive for occult blood, offered colonoscopy.  205 vs. 249 deaths from colorectal Ca in screening vs. nonscreening groups (RR 0.82; significant) (Lancet 348:1467, 1996-JW)
  2. UK study randomized 153,000 people 45-74yo to same method & schedule as above study; median f/u 7.8y.  360 vs. 420 deaths attributable to colorectal Ca in screening vs. control groups (sig.).  Note that 75% of the diagnosed colorectal Ca cases in the screening group were NOT diagnosed as a result of screening, i.e. presented by some other means! (Lancet 348:1463, 1996-JW)
  3. FOBT Q2y x 10y vs. haphazard screening, over 11y, was ass'd with a RR of colorectal Ca mortality of 0.84 (sig.) in a trial of 90,000 pts 45-75yo invited or not invited to participate in FOBT screening based on the province where they resided (Gastroent. 126:1674, 2004--JW)
  4. Immunochemical testing of stool for occult blood--More sensitive and specific than standard guaiac FOBT.
  1. Flexible sigmoidoscopy
    1. In an unrandomized prospective study in 2,146 pts with normal baseline flexible sigmoidoscopy, some of whom had f/u flex sig after 3y and some of whom had it at 5y, there was no sig. diff. in incidence of advanced neoplasia between the two groups. (Am. J. Gastroent. 101:1329, 2006--JW)
    2. In a study in 56,000 pts 55-64yo randomized to one-time flex sig vs. "usual care", with colonoscopy for any positive findings after flex sig, only 65% in the flex sig group actually had it done.  In intention-to-treat analysis, 7y colorectal Ca mortality was not sig. diff in the two groups, but for pts who underwent screening, it was sig. lower in screened group (RR 0.41) (BMJ 338:b1846, 2009-JW)
    3. In a study in 170,432 pts 55-64yo randomized to flexible sigmoidoscopy (one time) vs. no screening, in intent-to-treat analysis, over mean 11y f/u, the screening group had sig. lower incidence of distal colon Ca diagnosis (RR 0.64) and colorectal Ca death (RR 0.69) (Lancet 375:1624, 2010-JW)
  1. Colonoscopy
  1. Risk of bowel perforation is about 0.1%
  2. Screening colonoscopy with colonoscopic excision of polyps reduces colorectal cancer mortality by 53% (NEJM 2012-ref?)
  3. 3121 pts 50-75yo underwent screening colonoscopy. 37.5% had any neoplasm, 10.5% had "advanced disease" (tubular adenoma 1cm or greater, villous adenoma, adenoma w/high-grade dysplasia, or invasive carcinoma). 4.1% had advanced disease proximal to the descending colon. Of pts with no adenomas distal to splenic flexure, 2.7% had advanced proximal disease. 10 pts had "serious" complications from colonoscopy. (NEJM 343:162, 2000--JW)
  4. 1994 pts > 50yo underwent screening colonoscopy; 2.5% had an "advanced" proximal neoplasm (polyp or polypoid lesion w/villous features, high-grade dysplasia, or Ca), including 1.5% of the pts with no distal lesions. 1 pt had colonic perforation (NEJM 343:162, 2000--JW)
  5. 2885 pts all had FOBT then screening colonoscopy; 306 had "advanced neoplasia" (adenoma with > 10mm duration, villous features, or high-grade dysplasia; or invasive Ca); of those, only 76% had either positive FOBT or findings that would have been noted on flex sig (lesions in rectum and sigmoid colons) (NEJM 345:555, 2001--JW)
  1. CT colonography a.k.a. "virtual colonoscopy"
    1. Involves rectal air insufflation
    2. Sensitivity is low for small polyps, particularly < 5mm in diameter which constitute 80% of colorectal neoplasms
    3. In a study of 205 pts who underwent both virtual colonoscopy using spiral CT w/oral contrast and conventional colonoscopy, virtual colonoscopy had sens 62% and spec 71% for identifying lesions seen on colonoscopy, BUT had neg predictive value of 99% for lesions of 10mm diameter or larger (Gastroent. 125:304, 2003--abst)
    4. In a study of 1233 asymptomatic average-risk adults (mean age 58yo), all of whom underwent CT "virtual colonoscopy" and conventional colonoscopy, sensitivity for "advanced lesions" (polyps > 9mm or smaller but with advanced histology) was 92% with CT vs. 88% with colonoscopy (NEJM 349:2191, 2003--JW)
    5. In a comparative study in 615 pts > 50yo referred for routine colonoscopy, who underwent both colonoscopy and CT colonography, the latter had sensitivity of 39% and 55% for having at least 1 lesion of 6mm diameter or more and 10mm diameter or more, respectively (JAMA 291:1713, 2004--abst)
    6. In a study of 203 pts (about 50% asymptomatic) who underwent CT colonography followed several days later by colonoscopy, CT had sensitivity of 96% for polyps > 7mm in diameter and 86% for those < 7mm (Gastroent. 127:1300, 2004--JW)
    7. In a comparative study of 249 pts felt to be at increase risk for colorectal cancer, all of whom underwent CT colonography then colonoscopy, for detection of lesions 10mm or greater, CT had sens/spec of 84%/92% (Gastroent. 127:41, 2004--abst)
    8. In a study in 614 pts who underwent barium enema, CT colonography, and colonoscopy, sensitivity of CT colonography for lesions 10mm or larger (gold standard was taken as positive findings on any of the 3 tests) was 59%; for colonoscopy it was 98% (sig. greater than CT colonography); similar differences noted for lesions < 10mm in size (Lancet 365:305, 2005--abst)
    9. In a study in 937 people who were asymptomatic but at increased risk of colorectal Ca due to family history, personal history of positive FOBT, or personal history of colorectal adenomata, all of whom underwent CT colonography then colonoscopy on the same day, CT colonography had sensitivity of 85.3% for advanced neoplasia found on colonoscopy (JAMA 301:2453, 2009-abst)
  1. Magnetic Resonance Colonography--With MR-contrast enema
    1. In one study comparing MRC w/colonoscopy in 70 pts requiring colonoscopy, sensitivity/specificity was 96%/93%, respectively for identifying polyps of > 1cm in diameter (Gatroent. 119:300, 2000--JW)
    2. In another such study with 177 pts, sensitivity/specificity was 93%/99%, respectively for identifying polyps > 1cm in diameter (Radiol. 216:383, 2000--JW)
  1. Fecal DNA analysis
    1. Had sensitivity/specificity of 52%/95% for Ca (18% for cancer-or-advanced-adenoma) compared with colonoscopy in a cohort of 2,507 average-risk asymptomatic pts (mean age, 70) (NEJM 351:2704, 2004--JW)
  1. Serum markers
    1. C3a anaphylatoxin (C3a-desArg) shows promise in some early studies (Gastroent. 131:1020, 2006--JW)
  1. Capsule endoscopy
    1. In a study of 328 pts (mean age 59yo) with known or suspected colorectal neoplasia who went capsule endoscopy AND colonoscopy, the capsule had sensitivity of 64% for polyps > 5mm, 73% for advanced adenomata, and 74% for cancer. (NEJM 361:264, 2009-JW)
  1.  Note that race and gender may affect site of occurrence of colon Ca--in a retrospective study of 38,391 pts with colorectal Ca, incidence of proximal (up to and including descending colon) colorectal Ca was higher in black than in white population and distal colorectal Ca was higher for male than for female pts in both races (Cancer 80:193, 1997--AFP)
  2. Risk factors for proximal neoplasias in pts found to have adenomas on screening sigmoidoscopy: Age > 65, first-degree relative with colorectal Ca, multiple adenomas on sigmoidoscopy, or villous features in an adenoma found on sigmoidoscopy (JAMA 281:1611, 1999--JW)
  3. Surveillance after diagnosis & removal of adenomatous polyps
    1. Most common practice is colonoscopy Q3-5y
    2. Barium enema missed many adenomas seen on colonoscopy in one study of 580 pts with h/o adenomatous polyps (NEJM 342:1766, 2000--JW)

V. Prevention of colorectal cancer

  1. Aspirin/NSAIDs for prevention
  1. 22,000 adult males in the Physicians' Health Study randomized to ASA 325mg QOD vs. placebo; after 5y subjects chose whether or not to take ASA. After 12y f/u, no sig. diff. in incidence of colorectal Ca between the 2 original groups or between men choosing to take ASA > 2x/wk vs. men taking ASA less frequency (Ann Int. Med. 128:713, 1998--JW)
  2. In a retrospective analysis of 100,000 people > 65yo found that > 2y of cumulative NSAID use in prior 5y ass'd with RR of 0.49 of being dx'd with colorectal Ca compared with nonusers; no reduction in risk for < 3mos of use (no association w/dosage seen) (Arch. Int. Med. 159:161, 1999--JW)
  3. In a prospective study of 82,911 women in the Nurses' Health Study, over 20y, incidence of colorectal Ca was sig. lower in women who used ASA > 649mg/wk (RR 0.77) c/w those who used less or not at all (became sig. only after 10y of use), and was also sig. lower in women who used non-ASA NSAIDS 6-14 tabs/wk (RR 0.66) (JAMA 294:914, 2005--abst)
  4. In a study in 2,035 pts with colorectal adenomata randomized to Celecoxib 200-400mg/d vs. placebo, over 3y, celecoxib recipients had sig. lower incidence of colorectal adenomata (38-43% vs. 61%) and advanced adenomata (6-8% vs. 17%)  ("APC" Trial; NEJM 355:873, 2006--JW)
  5. In a study in 5,139 men randomized to ASA 300-500mg/d vs. no ASA x 5-6y, incidence of colorectal Ca over 10y was sig. reduced (HR 0.6). In another study in 2,449 pts with recent CVA randomized to ASA (300mg/d or 1200mg/d) vs. placebo x 1-7y, incidence of colorectal Ca over 10y was sig. reduced (HR 0.6) (Lancet 369:1603, 2007--JW)
  6. In a meta-analysis of 4 trials of ASA vs. placebo with mean f/u 6y, daily low-dose ASA for > 5y was associated with sig. reduced incidence of colorectal Ca (1.5% absolute reduction in 20y incidence from 4% to about 2.5%) and colorectal Ca-mortality (absolute risk reduction 1.8%).  All doses of 75mg or greater had similar effects. (Lancet 376:1741, 2010-JW)
  1. Postmenopausal HRT for prevention
  1. 59,000 postmenopausal women in Nurse's Health Study followed prospectively x 14y. Current use of HRT (75% on estrogen-only) ass'd with RR 0.65 for development of colorectal Ca; duration of use didn't affect (Ann. Int. Med 128:705, 1998--JW)
  1. Folic acid supplementation for prevention
  1. The Nurses' Health Study prospectively studied 88,756 female nurses who were questioned about diet and use of supplements; of 14y f/u, after multivariate analysis, dietary folate intake (including from multivitamins) of > 400ug ass/d with RR 0.69 of colorectal Ca compared with < 200ug/d; statistically sig. after 15y of high folate intake. No effect of Calcium or vitamins A, E, C, or D. (Ann. Int. Med. 129:517, 1998--JW)
  1. Dietary fiber for prevention of colon Ca--may not be effective
  1. In a prospective study of 90,000 women in the Nurses' Health Study followed for > 15y, dietary fiber intake was not ass'd with risk of colorectal Ca or adenoma; still no ass'n on multivariate analysis including analyses of subgroups defined by type of fiber (NEJM 340:169, 1999--JW)
  2. In a randomized trial of high-fiber, low-fat diet vs. "usual" diet in 2079 pts with h/o colonic adenomas, there was no difference in adenoma recurrence over 4y f/u (NEJM 342:1149, 2000--JW)
  3. In a randomized trial of 1429 pts with h/o colonic adenomas, addition of a high-fiber cereal to usual diet was not ass'd with a sig. difference in risk for adenoma recurrence over 3y f/u (NEJM 342:1156, 2000--JW)

VI. Surveillance after diagnosis of colorectal cancer

  1. In a randomized study of 325 pts s/p curative resection of colon ca, standard surveillance (hx/px, FOBT, CEA, and LFT's Q3mos x 2y then Q6mos) vs. "intensive" surveillance (the same plus yearly colonoscopy, liver CT, and CXR) showed no sig. diff. in survival at 5y (Gastroent. 114:7, 1998--JW)
  2. In a meta-analysis of 5 RCT's with total 1342 pts of intensive f/u after curative resection for colon Ca (involved various uses of colonoscopy, CEA, liver imaging, and CXR), intensive surveillance ass'd with sig. reduced all-cause mortality (RR 0.81). The 4 trials using CT and frequent CEA measurements ass'd with even lower RR (0.73) for all-cause mortality. (BMJ 324:813, 2002--JW)

VII. Treatment of colorectal cancer

  1. Surgery
  2. Chemotherapy (usually 5-FU + either levamisole or folinic acid)--beneficial in stage III but not stage II colon Ca
    1. Response to chemotherapy was sig. greater in pts with "Microsatellite Instability" (a type of DNA change) in their tumors in a nonrandomized trial of 656 pts with Dukes' C colorectal Ca (Lancet 355:1745, 2000--JW)
    2. Hepatic arterial chemotherapy for hepatic mets (after resection of hepatic mets)--Ass'd with sig. higher 2y survival (86% vs. 72%) in a randomized trial of 156 pts (NEJM 341:2039, 1999--JW)
    3. In a meta-analysis of 13 randomized trials involving 1365 pts studying chemotherapy (9 trials involved fluorouracil) vs. no chemo for metastatic colon Ca, chemo ass'd with sig. better median survival (11.7mo vs. 8mo) and better quality of life (BMJ 321:531, 2000--JW)
  3. "Active specific immunotherapy" (I'm a little unclear on how this actually works--improves survival in stage II colon Ca--Lancet 353:345, 1999--JW)
  4. Resection of hepatic metastases--predictors of recurrence after resection; 5y survival after resection was 60% with none and 14% with all 5 in a series of 1,001 pts (Ann. Surg. 230:309, 1999--JW)
    1. > 1 hepatic met
    2. CEA > 200 ng/ml
    3. Any met > 5cm
    4. Node-positive primarytumor
    5. Disease-free interval of < 12mos between initial dx of colon Ca and detection of a met
  5. Aspirin for prevention of colorectal cancer-related mortality in pts with colon Ca
    1. In a prospective cohort study in 1,279 pts with colorectal Ca (stage I-III), over 12y f/u, regular use of ASA was associated with sig.  reductions in colorectal Ca-related mortality (RR 0.71) and overall mortality (RR 0.79) (JAMA 302:649, 2009-JW)
(Sources include Core Content Review of Family Medicine, 2012)