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screening for colon cancer

Indications: 1) health maintenance a) all persons age 50-75 years of age (USPSTF, ACP) (A recommendation) [95] - persons age 45-49 years of age as needed (B recommendation, USPSTF) [95] - all persons age 45-75 years of age (ACS, ACG) [62,79,86,94] - screening resources better utilized for older unscreened individuals - asymptomatic adults with 15-year risk < 3% may not need screening [88] - use QCancer calculator to calculate risk [88] - screening colonoscopy in elderly > 75 years with limited life expectancy is associated with increased risk of complications [102] - colorectal cancer is rare [102] b) any acceptable modality of screening [10] - colonoscopy, sigmoidoscopy, fecal immunochemical testing (FIT) - fecal immunochemical testing (FIT) or high-sensitivity guaiac-based fecal occult blood testing every 2 years [89,95] - Colonoscopy every 10 years [89] - colonoscopy of no benefit if fecal immunochemical testing is negative [91] - flexible sigmoidoscopy every 10 years + FIT every 2 years [89] - air contrast barium enema formerly recommended as alternative - preferred strategy is the one most likely completed by patient [10] c) discontinue routine screening age > 75 [21,29,79] - screening optional for elderly with life-expectancy > 10 years [45] - may be beneficial for older patients (76-85 years) if they are healthy enough for cancer treatment, don't have other factors that might limit life expectancy, or haven't been previously screened [56] - benefit is small in elderly > 75 years of age (C recommendation) [95] - reduction in colorectal cancer mortality in elderly > 75 years of age without comorbidities whether or not they have been previously screened (RR=0.6) [96]; absolute risk reduction & number needed to treat not found [96] - screening offers modest benefit in elderly 70-74 years - in this poplulation 8 year risk for colon cancer: RR = 0.84, absolute risk reduction = 0.43%, NNT = 236 to identify 1 case of colon cancer [63] - screening offers less benefit in elderly 75-79 years - in this poplulation 8 year risk for colon cancer: RR=0.96, absolute risk reduction 0.13%, NNT= 769 to identify 1 case of colon cancer [63] d) routine screening for elderly 76-85 with consistently negative screenings since age 50 not indicated [19] - screening for elderly 76-85 on case by case basis [62] e) do not screen elderly > 85 years of age [19,62,79] f) a computer model suggests screening of previously unscreened patients without comorbidities up to age 86 is cost effective [50] g) Canadian Task Force on Preventive Health Care - adults aged 50-74 should be screened every 2 years with fecal occult blood testing, either guaiac or FIT, or every 10 years with flexible sigmoidoscopy (adults > 60 years of age) [59] - adults > 75 years should not be screened [59] h) environmental & genetic factors may improve risk stratification & enable tailoring of screening recommendations [75] - screening of low-risk individuals may be cost-effective if begun at age 56 for men & 64 for women [75] 2) patients with family history of colon cancer a) 1st degree relative with colon cancer at age < 60 years; 1] begin screening at age 40 any modality or 10 years earlier than the time of diagnosis (whichever is younger) 2] colonoscopy preferred method of screening [82] - if normal, repeat every 5 years with FIT every 1-2 years [82] b) 2 1st degree relatives with colon cancer at age > 60 years; 1] begin screening at age 40 any modality - colonoscopy preferred method of screening [82] 2] if normal, repeat every 5-10 years c) 1st degree relative with advanced adenomatous polyp at age < 60 years: 1] begin screening at age 40 any modality or 10 years earlier than the time of diagnosis (whichever is younger) 2] colonoscopy preferred method of screening [82] - if normal, repeat every 5 years d) 1st degree relative with advanced adenomatous polyp at age > 60 years: 1] begin screening at age 40 years (American College of Gastroenterogy) [94] 2] colonoscopy preferred method of screening [82] - if normal, repeat every 10 years e) risk conferred by affected half-sibling is similar to that conferred by first-degree relatives [84] f) 2nd or 3rd degree relatives with adenomatous polyps or colon cancer: - treat as average risk g) hereditary nonpolyposis colon cancer (Lynch syndrome) risk - (3-2-1 rule) 3 affected family members; 2 generations affected; 1 under age 50 years - begin screening at age 20-25 years or 10 years prior to the earliest time of diagnosis [10] - repeat every 1-2 years [10] h) hereditary polyposis syndromes - familial adenomatous polyposis coli risk - begin screening at age 10-12 with sigmoidoscopy or colonoscopy - repeat every 1-2 years prior to colectomy [10] - see specific entity i) pancolitis (ulcerative colitis or Crohn's disease): - begin screening colonoscopy every 1-2 years 8-10 years after initial diagnosis [10] j) screening should occur at a young age & occur often if hereditary non-polyposis colorectal cancer [7] k) if not hereditary non-polyposis colorectal cancer, screening may begin at age 45 [7] 3) special case of inflammatory bowel disease a) colonoscopy beginning 8-10 years after diagnosis, then at intervals of 1-2 years [10] b) colonoscopy should include biopsy 4) personal history of cancer - women with a history of breast cancer before age 50 are at higher risk for colorectal cancer [68] - breast cancer in women > 50 years of age not associated with increased risk for colon cancer [68] - no need to alter screening frequencies Contraindications: - no benefit for screening [13] 1) men age 75-84 with poor health status 2) men > 85 years of age with average or poor health status 3) women > 90 years of age with average or poor health status 4) elderly > 75 years with limited life expectancy [102] * up to 50% of veterans feel that limited life expectancy should not influence screening decicions [83] Benefit/risk: number needed to screen 1) screening 1000 persons for 10 years save 1 colorectal carcinoma related death [33] - compare with 1 serious complication per 1000 colonoscopies (see colonoscopy) 2) number needed to screen to detect one advanced adenoma with flexible sigmoidoscopy is 13 in men & 27 in women [36] 3) number needed to screen to detect one colorectal carcinoma for flexible sigmoidoscopy was 184 in men & 351 in women 4) number needed to screen to detect one advanced adenoma with fecal occult blood testing (FIT)is 41 in men & 111 in women 5) number needed to screen to detect one colorectal carcinoma with fecal occult blood testing (FIT) is 209 in men & 507 in women 6) no colorectal cancer screening methods reduce all-cause mortality [62] - flexible sigmoidoscopy may be associated with reduced mortality risk (RR = 0.975); 3 deaths could be averted per 1000 people screened within 12 years [71 - biennial screening with fecal immunochemical testing is associated with 34% fewer advanced colorectal cancers & 40% fewer colorectal cancer- related deaths [93] 7) colonoscopy in presumptively healthy men & women 55 -64 years of age in Poland, Norway, Sweden, & the Netherlands reduced 10 year risk of colon cancer [99] - number needed to screen to prevent 1 case of colon cancer = 455 [99] 8) colonoscopy reduces risk of colorectal cancer by 18% but does not reduce 10 year risk of cancer-related death [100] Epidemiology: - risk factors combined into an 8 point score: - family history, smoking, higher body-mass index, less physical activity, unhealthy diet, alcohol use, tall stature, & lack of aspirin use [97] - 0-2: 10 year risk of colorectal cancer = 0.85% - 0.15% mortality, 0.08% with colonoscopy [97] - 6-8: 10 year risk of colorectal cancer = 1.99% - 0.44% mortality, 0.22% with colonoscopy [97] Pathology: - screening for colon cancer is feasible as a result of the 10-15 year time course for the transformation of an adenomatous polyp into colorectal adenocarcinoma, ample time to detect & remove an adenoma Laboratory: 1) annual stool guaiac beginning at age 50 [2,19]; - detects 8% of all advanced adenomas & 20% of all cancers (single screening) [36] 2) high-sensitivity fecal occult blood testing (FOBT) or fecal immunofluorescence testing (FIT) annually age 50-75 years (ACP) [54] - fecal immunochemical testing (FIT) preferred screening test [59] every 2 years [76] - multiple-round FIT detects more neoplasia than one-time sigmoidoscopy or colonoscopy [87] - participation rate is higher with FIT (77%) than with sigmoidoscopy (31%) or colonoscopy (24%) [87] - lower incidence of interval colorectal cancer after negative FIT than after negative guaiac FOBT [80] - follow-up with live phone calls may be more effective in getting patients to complete home FIT testing vs text messaging or other reminders [73] - follow-up colonoscopy within 9 months for positive FIT [67] - longer delays to colonoscopy associated with higher risks for cancer findings [67] - poor performance in detecting advanced neoplasia limits its use in screening high-risk patients [70] 3) stool DNA testing a) exfoliated cells in stool specimens [1,16,30] b) testing every 3 years (American Cancer Society) [69,79] c) not yet recommended by USPSTF d) procedure - K-ras, p53, APC, bat-26, 'long DNA' [1] - combination 'DNA integrity', hypermethulation of vimentin gene 88% sensitivity, 82% specificity [16] - false positive vimentin gene methylation associated with older age [16] - K-ras mutant amplification with alpha-actin control detects colon carcinoma & large adenomas [30]; test also quantifies hemoglobin e) colorectal carcinoma: sensitivity=85%, specificity=90% f) for adenomas > 1 cm: sensitivity: 63% g) fecal RT-PCR of 10 DNA markers + fecal hemoglobin h) Cologuard tests patients' stool for hemoglobin, DNA methylation & mutation markers & total amount of DNA .recommended March 2014 i) Cologuard Plus FDA-approval 2024 - tests for three novel methylated DNA markers & fecal hemoglobin - sensitivity of 95% for colorectal cancer & 43% for advanced precancerous lesions - 94% specificity with no findings on colonoscopy [106] 4) multitarget stool RNA (ColoSense) detects colorectal neoplasia-associated RNA & presence of occult hemoglobin in human stool [105] 5) cell-free DNA in plasma for colorectal cancer screening (Shield DNA test) detects 88% of stage 1,2, & 3 colorectal cancers [104] - only detects 13% of precancerous lesions - false positives 10% - Guardant's Shield test (FDA-approved) detects 83% of colorectal cancers [104] 6) digital protein truncation assay [3] 7) lymphocyte expression of IGF-2 may be useful [5] (see IGF-2) 8) C3a anaphylatoxin (C3a-desArg) a) increased in sera of colorectal cancer patients b) 96.8% sensitivity & 96.2% specificity c) also increased in patients with colorectal adenomas [14] 8) Epi proColon measures plasma levels of methylated Septin 9 DNA [46] - FDA-approved, but sensitivity only 48%, thus not recommended 10) serum carcinoembryonic antigen (CEA) is not recommended as a screening test [10] Special laboratory: 1) colonoscopy a) every 10 years age 50-75 (ACP) [54] - Canadian Task Force on Preventive Health Care recommends against colonoscopy as a primary screening tool in asymptomatic adults > 50 years of age [59] - fecal immunochemical testing (FIT) preferred screening test [59] - a single screening colonoscopy may suffice [76,92] - advanced neoplasia within 10 years after negative colonoscopy uncommon [90] b) every 10 years may be better than sigmoidoscopy [6] c) screening colonoscopy beneficial for Medicare enrollees [15] 2008 Guidelines [18] average risk 50 years of age& older d) 57% reduction in colon cancer deaths [24] e) 56% risk reduction for right-sided colon cancer [23] f) 84% risk reduction for left-sided colon cancer [23] g) significantly more protective than sigmoidoscopy only in death rates from proximal cancers [48] h) detection of advanced neoplasia higher with colonoscopy (9.1%) than with sigmoidoscopy (7.4%) or FIT (6.1%) [87 i) randomized trial-level evidence of reduced cancer- specific mortality does not exist for colonoscopy [51] 2) flexible sigmoidoscopy (tier 2) a) every 5 years age 50-75 years (ACP) [12,54] with or without annual FOBT or FIT [54] b) every 10 years with annual FIT (not stool guaiac) (USPSTF) [56] c) once may be better no screening [21] d) once age 55-74 years reduces colorectal carcinoma incidence & mortality [27,32] e) benefit limited to colorectal carcinoma distal to the splenic flexure [32] f) 19% of patients who refuse sigmoidoscopy accept fecal occult blood testing [36] g) one time screening of men 50-64 years of age reduces cancer related mortality (RR = 0.73) [51] - does not reduce colon cancer or mortality in women [78] h) one time screening at age 60 reduces incicence of colorectal cancer after 11 years (NNT=191) & 17 years (NNT=98) but no reduction in mortality [66] 3) video capsule endoscopy (tier 3) [69] - inferior to colonoscopy [20] Radiology: - CT virtual colonoscopy (tier 2) every 5 years [14,69,95] - double contrast barium enema every 5 years [18] - no longer recommended [69] Notes: 1) digital rectal exam yearly after age 40 no longer recommended - extremely insensitive - 90% of tumors are beyond the distal rectum [8,10,11] 2) options for detecting both adenomatous polyps & cancer - flexible sigmoidoscopy every 5 years - improves survival [10] - computed tomography every 5 years - colonoscopy every 10 years - double-contrast barium enema every 5 years - 2008 guideline has dropped the recommendation for barium enema, citing its low sensitivity & declining use [19] - no longer recommended [69] 3) options primarily for detecting cancer - guaiac fecal occult blood testing annually - fecal immunochemical testing annually - stool DNA test (every 3 years) 4) annual high-sensitivity fecal occult blood testing equivalent to colonoscopy at 10-year intervals in years of life gained [19] 5) fecal occult blood (FOB) vs colonoscopy - FOB more likely to be accepted by patients than colonoscopy - FOB & colonoscopy detect colon cancer equally [29] - colonoscopy more effective than in detecting ademomas, including advanced adenomas [29] - polypectomy reduces colon cancer mortality [29] - comparison of mortality FOB vs colonoscopy not done [29] 6) screening tool based on 5 variables may be useful for selecting patients for less invasive screening [55 - age, sex, waist circumference, cigarette smoking, family history of colorectal cancer 7) compliance with screening recommendations - 62% of adults comply with USPSTF recommendations for screening, yet 50% of colon cancers present at late stage [22] - compliance is improved if patients either offered FOBT or given a choice of FOBT or colonoscopy [31] - awareness of personal risk does not increase screening rates [52] - electronic reminders do not affect screening rates [25] - mailing FOBT kits directly to patients is the most effective means of increasing colon cancer screening rates [35] - outreach program may improve screening rates [72] colonoscopy more so than FIT - patient navigators & automated reminders for clinicians improve follow-up of positive FOBT or FIT [74] - active distribution of fecal blood testing is most effective means of increasing screening rate - endoscopists recommend follow-up colonoscopy at intervals often shorter than guideline-recommended intervals [53] 7) canines (dogs) can be trained to detect colon cancer [26] - compared with colonoscopy, a labrador retriever achieved a sensitivity of 91% & specificity of 99% with breath samples& 97% & 99% with watery stool samples in distinguishing patients with colon cancer vs controls - results were similar between early & late-stage cancers [26] 9) older age & male sex are independent predictors of advanced colorectal neoplasia [37] 10) colorectal cancer risk calculator from the National Cancer Institute - incorporates incorporates multiple risk factors: gender, age, BMI, vegetable intake, use of aspirin NSAID, exercise, previous colon cancer screening, smoking, estrogen status (women) & family history [64] === out-of-pocket costs === - 1 in 6 individuals undergo colonoscopy within 6 months of stool testing - out-of-pocket costs for colonoscopy incurred by ~1/2 who are commercially insured & by > 3/4 who are covered by Medicare, with costs increased when polypectomy performed [98]

Related

adenocarcinoma of the colon &/or rectum cell-free DNA in plasma for colorectal cancer screening; Shield DNA test colonoscopy colorectal polyp fecal DNA testing fecal occult blood; fecal immunochemical testing; fecal immunofluorescence testing, multitarget stool DNA (mt-sDNA, FOB, FIT, iFOBT, ColonCARE, Hemoccult, ICT, InSure)

General

screening for cancer

References

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