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Colorectal Cancer Screening and Prevention

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Colorectal Cancer Screening and Prevention Powered By Docstoc
					Colorectal Cancer Screening and
           Prevention
                  RFUMS
    The Chicago Medical School 2005
          David R. Rudy, MD, MPH
           Professor and Chairman,
        Family and Preventive Medicine
      Preventive Medicine MTD 601
                   Prevention

 Primary prevention: keeping a disease
  process from happening (smoking cessation
  prevents (95% of) lung cancer
 Secondary prevention: interruption of a
  disease process in a curable phase (Ca
  cervix, colon - place for screening)
 Tertiary prevention: stopping or retarding a
    symptomatic disease (improving risk status after
    MI)
       Terms of Epidemiology

 Incidence - new cases over unit of time/unit
  of population
 Prevalence - number of cases at a point in
  time/unit of population
 Sensitivity (of a test) - proportion of cases
  diagnosed by a test
 Specificity - proportion of population
  without the disease that will test negative
        Criteria for screenability
 1. Condition has significant effect on life
 2. Significant treatment available
 3. Asymptomatic period of diagnoseability
 4. Treatment in asymptomatic phase yields result
    superior to delaying until symptoms appear
 5. Tests of reasonable cost- sensitivity and
  specificity appropriate for population risk
 6. Incidence sufficient to justify cost
                   Terms

 Positive predictive value - chance of a
  positive test signifying disease
 Negative predictive value - chance of a
  negative test result signifying absence of
  disease
 None of the forgoing can be told without
  knowledge of prevalence of the disease
           Colon Cancer: Causation

   Combined environmental and genetic:
    Environmental causes include diet low in
    fiber and gut bile salts, higher in fat.
    (Harrison's Principles of Medicine; 11th Ed). Genetics to be addressed in 2.

   95% arise from adenomas; 70-90 % from
    adenomatous polyps (10-30 % from sessile
    adenomas).
    TYPE     PREVALENCE     % MALIGNANT



 Tubular adenoma 75%             5%
 Tubulovillous       15 %       22%
 Villous adenoma 10 %           40 %
 Weighted chance (100 %) 10.5%
 15-30% of (US) pop. adeno- polyps/life;
 Lifetime colon Ca risk 2.5-2.6% (sporadic).
       Hyperplastic polyps

Comprise up to 1/3/ of all polyps: have no
malignant potential - recognized only hy
            histopathology
            CRC locations:

 About    1/3 of polyps arise proximal to
  the splenic flexure (cephalad).
 (I,e,. 2/3 of polyps can be found by
  sigmoidoscopy
 About 1/2 of colorectal carcinomas
  arise proximal to the splenic flexure.
 (1/2 cancers found by sigmoidoscopy
       Polyps to Carcinoma

 Dwell  time average 10 years, therefore
  five year interval between most screen
  methods is safe.
 Odds of polyp becoming cancer in the
  individual case may be inferred to be
  about 1 in 10 within a lifetime.
    Relative significance of Colorectal
                Carcinoma

   Tumor               Incidence             Cause specific Case
                                               mortality     Mort
   Lung               172,570                  163,510      95%
                                             M:F =55%:45%
 CRC      145,290                               56,290      39%
 Breast   212,930                               40,870      19%
 Prostate 232,090                               30,350      13%
    Jemal A, Tiwari RC, Murry T, Ward E , Samuels A, TiwariRC, Ghafoor A, Feuer EJ,
    Thun M: Cancer Statistics, 2005. CA: Cancer J. for Clin 2005; 55(1): 10-30
    “BURDEN OF SUFFERING”
              1
   145,290 incidence CRC/US est. for ‟05;
   56,290 deaths US mortality F~M
 Second   leading cause of cancer death
  US, without sex distinction,
 - albeit well below lung cancer.
 Case Mortality 38.7% (Jemal A, et al: Cancer Statistics,
    2005. CA: Cancer J. for Clin 2005; 55(1): 10-30
     Case Mortality CRC

  56,290 /year US mortality 2005
   ÷ 145,290 incidence CRC/US
= 38.7% approximate case mortality
Relative incidences CRC among five
  ethnic groups (see Table III 1B)
 Ethnic group                                                                     RR
 Indigenous                                 488                                   1.0
 Asian/PacIsl                               699                                   1.4
 Hispanic/Latino                            731                                   1.5
 Whites                                     988                                   2.0
 African                                   1103                                   2.26
   Cancer Incidence and Mortality Rates by Race and Ethnicity in the US 1996-2000 (Cancer Fact and
    Figures 2004, American Cancer Society)
    Relative mortality CRC among five
     ethnic groups (see Table III 1B)
 Ethnic group                                                                     RR
 Asian/PacIslanders                              27                               1.0
 Hispanic/Latino                                 29                               1.1
 Indigenous                                      30                               1.1
 African                                         40                               1.5
 Whites                                          42                               1.6
   Cancer Incidence and Mortality Rates by Race and Ethnicity in the US 1996-2000 (Cancer Fact and
    Figures 2004, American Cancer Society)
            Burden of Suffering 2:
           by colon vs rectal (2002)
 Colon Ca incidence: 105,500/US/yr
 Colon Ca mortality: 48,100/US/yr (2002)
  implies ~ 45% colon Ca case mortality
 Rectal Ca incidence: 42,000/US/yr
 Rectal Ca mortality: 8,500/Us/yr (2002)
  implies ~ 21% rectal Ca case mortality (02)
    Cancer Statistics, 2003. CA - Cancer Journ Clin. 2003; 53(1): 5-26
    Implications for increasing life
              expectancy
 CRC assumes exponentially increasing
  incidence with age
 The later the age onset of CRC the lesser
  the aggressiveness
 Thus, CRC with age shows an increasing
  incidence and decreasing case mortality
 But - secondary prevention (of progression
  of polyps) may neutralize that tendency
      (COLORECTAL CANCER; BURDEN OF
               SUFFERING)


 Incidence rate: /100,000 Pop./year,
 15/100,000 in 40-50 y.o.,
 >400/100,000 in > 80 y.o.[Frame, Paul S: J Fam
    Pract, 1986; 22(6): 511]
   Fourth cancer in incidence, behind prostate,
    breast and lung (third in each sex). Third
    in cancer deaths each sex after lung,
    prostate (males) and lung, breast (females)
    Characteristics of Colon Ca

 Left > Rt lesions in men (earlier
  diagnosis);
 Right > Lft in women (worse prognosis).
 Patients > 70 more likely to present in
  Stages A or B.
 Younger patients have more aggressive
  disease for a given stage
      Characteristics of CRC,
           ethnicity(1)
 African-  and Hispano-Americans less
  likely to present in stages A or B.
 Asians have presentation patterns
  similar to non-Hispanic whites.
 Inflammatory bowel disease is a risk,
  may be considered premalignant.
     Characteristics of CRC,
          ethnicity(2)
 Askenazi Jews have lifetime risk of
 CRC equal to Caucasians w/ 1st
 degree relative with adenomatous
 polyp or CRC = three times the
 lifetime accumulative risk (2.5% ->
 7.5%)
 Characteristics of Colon Ca,( 3)

 Presentationwith hematochezia
 renders a better prognosis (only 19%
 die of disease)
 After presentation with any other
 symptom 83% die of disease (e.g. BM
 change, obstruction).
    GENETICS AND COLON
        CANCER (1):
 Lifetime risk of CRC = 2.5%;
 Tripled when have first degree relative
  w/ adenomatous colon polyp(s) or
  colon cancer - to 7.5
 Increasing life expectancy expected to
  increase cumulative incidence
 Several specific genes identified
    Five -10% of colon Ca occurs in
      definite hereditary patterns.
 Adenomatous polyposis syndromes (APS)
  account for about 9-10% of CRC:
 Hereditary “Non-polyposis” Colon Cancer
  (HNPCC, Lynch syndrome) - accounts for
  about 6%. Characterized by both
  pedunculated and sessile premalignant
  polyps,
      Adenomatous Polyposis
           Syndromes
 Familial Adenomatous Polyposis (FAP):
  1-2 % of CRC
 100s -> 1000 CR polyps beginning early in
  life. All develop CRC by age 40.
 Gardner‟s syndrome: numerous polyps, risk
  of colon cancer, plus osteomas, epidermoid
  cysts and sesmoid tumors.
 Turcot‟s syndrome (assoc.. CNS tumors).
     CLINICAL PRESENTATION,
            (BRIEFLY)

 Hematochezia (distinct from melena): If
  first symptom, tends to indicate the
  descending colon - with better prognosis.
 Change in bowel habit: e.g. alternating
      constipation and diarrhea.
 Obstipation to clinical lower bowel
  obstruction.
        COLORECTAL CANCER
      SURVIVAL (Dukes Stages, 5 y):
 Stage A: limited to mucosa and submucosa 90%
 Stage B: extends into muscularis or serosa 60-75%
 Stage C: one positive node - 69% six or more positive
  nodes, 27%
 Stage D: mets. to liver, bone, lung 5%
    . COLORECTAL CANCER
      SURVIVAL(descriptive):
 Overall 5 yr Survival About      55-75%
  (reciprocal of 39% case mortality = 61%)
 With localized disease           80-90%
 With regional metastases          36%
 With distant metastasis           29%
 With disseminated disease           5%
      Screening Methods‟ success,
           simulation model
   Meth FOBT FS FS/OBT DCBE DCBE BE/FS Colnoscpy
   q# yr       1     5       5         5       10         5     10
   DcrCases 2378 1975 3087           3394 2812          3875 3570
   DcrDths 1278 976 1556             1629 1418         1843 1690
   DcrMort 53.5% 40.1% 65.1% 68.1% 59.3% 77.1% 70.7%
   Decr = decrease [cases, deaths (net after complications); mortality rate
    as percent]
   * Based on expectation of 4988 cases CRC/100,000 pop
    cumulative from the ages of 50 through 85 yrs or death;
    and expectation of 2391 deaths due to CRC in this
    population, cumulatively (Winawer et al, Gastroenterology, Sept, 1997).
CRC Screening Guidelines according to
              AGA:
      Average Risk - Option 1
   Digital rectal examination/fecal
    occult blood (DRE/FOBT) start
    @ 50 years every yr (AGA):
    predicts 50% (or less) reduced
    mortality
   CRC Screening Guidelines:
    Average Risk - option 2
 Flexiblesigmoidoscopy every 5
 years (60 cm): Predicts only
 40% reduction of CRC
 mortality
  CRC Screening Guidelines:
    Average Risk option

3. FOBT + Flexible
 Sigmoidoscopy q 5 yr
 predicts 65% reduction
 CRC mortality
  CRC Screening Guidelines:
 Average Risk - options (AGA)

4.Dual Contrast BE
 every five yr.; Predicts
 68% reduction in
 mortality from CRC
 CRC Screening Guidelines:
 Average Risk - options (AGA)

5. DCBE every 10 yr.
 Predicts 59% reduction
 in mortality due to
 CRC
 CRC Screening Guidelines:
 Average Risk - options (AGA)


6. FS + DCBE every 5
 yr predicts 77%
 reduction in mortality
 due to CRC.
 CRC Screening Guidelines:
 Average Risk - options (AGA)

7. Colonoscopy every
 10 yr predicts 71%
 reduction in mortality
 from CRC
      Does CRC meet Criteria for
            screenability!
   1. Condition has significant effect on life (Yes)
   2. Significant Treatment available in curative
    phase (Yes)
   3. Asymptomatic period of diagnose-ability (Yes)
   4. Tx in the asymptomatic phase yields result
    superior to delaying until symptoms appear (Yes)
   5. Tests of reasonable cost- sensitivity and
    specificity appropriate for population risk (Yes,
    with some argument)
   6. Incidence sufficient to justify cost (Yes)
   CRC Screening Guidelines:
     Normal Risk (ACS)
 Foraverage risk status start @ 50 years
 of age
 or start @ 40 years q 1 yr (AGA) if
 1st degree relative w/ adenomatous
 polyp or CRC
    CRC Screening Guidelines:
       Higher Risk (ACS)
 Presence of Familial Adenomatous
  Polyposis:
 Starting @ 10 y.o., DRE + colonoscopy;
  if polyps present repeat in 1 year, otherwise
  repeat in 3 years (ACS per Jessup et al: CA Cancer J
      Clin 1997; 47:70-92)
     CRC Screening Guidelines:
        Higher Risk (ACS)
 Presence of HNPCC:
 Starting in the teen years, proceed as with
  FAP [DRE + colonoscopy]; if polyps,
  repeat in 1 year, otherwise repeat in 3 years
  (ACS per Jessup et al: CA Cancer J Clin 1997; 47:70-92)]
    CRC Screening Guidelines:
       Higher Risk (ACS)
 Symptoms present:
 Starting at 25 years age, same as for 50
  without symptoms, average risk (DRE +
  FOBT + colonoscopy; if neg repeat in 3-5
  years)
    Clinical terms used in CRC

 Carcinoembryonic antigen (CEA): tumor
  marker - sensitive but not specific. Best
  used for follow-up after definitive surgery
 Synchronous: (as in polyps or cancers)
  existing at the same time as index cancer in
  a single patient
 Metachronous: cancers or polyps occurring
  subsequent to the index cancer or polyp
    Pre-operative Workup :
         Colonoscopy
 Synchronous cancer in 2%-7.2%
 Synchronous polyps: 12%-62%
 Most surgeons favor colonoscopy
  > DCBE
Pre-op carcinoembryonic antigen
             (CEA)
 Described by Gold and Freedman 1965
 Usually returns to normal within one month
  after (successful) excision
 If post-op fall to normal is f/b persistent
  steady rise signals recurrent cancer in 95%
        Primary Prevention CRC:

   ASPIRIN and other NSAIDs: 662,424
    adults tracked 1982 through 1988 for
    occurrence of CRC and whether or using
    aspirin (observational study): RR for CRC
    in those who used ASA > 15 times/month
    was 0.60 in men, 0.58 in women (Thun MJ et
    al: N Engl J Med 1991; 325:1593-96)
Primary Prevention of Adenomas

   793 subjects surveyed at 6 and 12 mos. into
    observation period, for ASA use Those who
    reported use on both questionnaires
    manifested fewer adenomas (OR = 0.52)
    (Greenberg: JNCI 1993;85(11): 912-16)
       Colon Ca genetics (1),
       “molecular approach”:
 Adenomatous polyposis coli gene (APC,
  actually APC suppresser), on chromosome
  5q, short arm),
 when defective (loss of heterozygosity
  [LOH]), allele allows submission to CRC.
 75% of adenomatous polyps have a
  mutation in the APC gene.
        Colon Ca genetics (3),
        “molecular approach”:
   „Deleted in colorectal cancer‟ (DCC)
  gene, also a suppresser.
 Other suppresser genes include
  „mutated in colorectal cancer‟
  (MCC), and p53.
 Oncogenes develop by mutation: they
  include ras, src and myc.
        Colon Ca genetics (4),
        “molecular approach”:
   Insulin like Growth Factor: 30% of
    "normal mucosa" of CRC patients have
    lost the imprinting of IGF2, an
    epigenetic alteration, as opposed to
    10% of healthy individuals.
                Pre-op
               2:Staging
 H&P, Chest XR
 Ck for evidence of tumor fixation; if
  present, ck for hepatomegaly,
 Rectal, pelvic (as applic) necessary
 Chest XR for synchronous lung met (10%
  will develop)

				
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