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					     Cancer
    Screening
              BY
         Assist. Prof.
ASHRAF YOSRY GENDIA, M.D.
Consultant of Clinical Oncology;
  Dr. Abdul Rahim Gari Cancer
        Center, Jeddah
             2006
What Is Cancer Screening?
   Appropriate cancer screening should
lead to early detection of asymptomatic
or unrecognized disease by the
application of acceptable, inexpensive
tests or examinations in a large number
of persons.
 The main objective of cancer
screening is to reduce morbidity
and mortality from a particular
cancer among persons screened.
  Table 1: Characteristics of Screening
     Tests versus Diagnostic Tests
        Screening                    Diagnosis
Applied to asymptomatic      Applied to symptomatic
groups                       individuals
Lower cost per test          Higher cost; all necessary
                             tests applied to identify
                             disease
Lower yield per test         Higher probability of case
                             detection
Lower adverse consequences   Failure to identify true
of error                     positives can delay treatment
                             and worsen prognosis
  Table 2: Evaluation of a Screening Test
                                 Truth (Diagnostic Classification)

Screening Test Results           Cancer Present        Cancer Absent
Positive                         True positive (TP)    False positive ( FP)

Negative                         False negative (FN)   True negative (TN)

Sensitivity = TP/FP + FN x 100

Specificity = TN/FP + TN x 100

PV+ = TP/TP + FP x 100

PV– = TN/TN + FN x 100
Accuracy = TP + TN/TP + TN +
FP + FN x 100
        Consequences of Screening

           Positive                        Negative
Improved prognosis of          Potential carcinogenic effects
detected cancers
                               Consequences of false-positives
Less radical treatment         and false-negatives

Reassurance with negative
test results

Resource savings            physical   psychological   economic
(reduced treatment costs)
Breast Cancer Screening
          Statistical Data

 In Saudi Arabia, 600 new breast cancer
patients registered annually according to
the national registry.

  In the United States, 211,300 new
invasive cases of breast cancer with
39,800 deaths due to the disease were
estimated to have occurred in the year
 2003.
     Widely accepted techniques for
        breast cancer screening

Mammography        Clinical breast examination   Breast self-examination
 Most of the
                               CBE                         BSE
benefit occurs       The evidence
when screened        suggests that a 5% to          Monthly BSE is
women are in         20% additional                 recommended
their 50s.           benefit in mortality           by American
                     reduction can be
                     achieved by adding a           Cancer Society
A reduction in      high-quality CBE               for women aged
breast cancer        yearly .
mortality around                                    20– 69 y.
18%.
                      Data suggest that
Latest              CBE may be most
recommendation       useful for women in
is annual            their 40s where
mammograms for       mammography may be
women aged 40        somewhat less
years and older.     efficacious.
Measures of Effectiveness                              (Randomized Controlled Trials)

  Year Age         Screening     Perio    Rando      Study    Control   Screen    Follo Reduction
 Begun at          Modality      dicity   mizati                          ed at   w-Up in Mortality
       Entry                     (Mo)        on                           First     (Y) Screen vs.
       (Y)                                                               Exami          Control/
                                                                        nation          Comparison
                                                                           (%)          Group

Stockhol   40–64   1-view MM      28      Cluster    39,164   19,943     81         8        0.80
m (1981)                                   : birth                                        (0.53–1.22)
                                          cohort
Gothenb    40–59                          cluster             28,809     84                  0.86
     urg           2-view MM      18        s age    20,724                        12
 (1982)                                                                                   (0.54–1.37)
                                              (Y)
                                           40–49
                                           50–59

 Canada             2-view MM     12       Individ   25,214   25,216                         0.97
  NBSS1    40–49                              ual:                      ~100b     11–16
                    and CBE               volunte                                         (0.74–1.27)
 (1980)
                                             ers
 Canada    50–59    2-view MM              Individ   19,711   19,694                         1.02
  NBSS2              & CBE vs.    12          ual:                      ~100b      13
                                          volunte                                         (0.78–1.33)
 (1980)             CBE only
                                             ers


CBE, clinical breast examination; HIP, Health Insurance Plan ; MM, mammography.
Nonrandomized Clinical Trials
   The U.S. Breast Cancer Detection Demonstration
Project screened 280,000 women aged 35 and older in
28 centers annually with mammograms and CBE. A
benefit was seen for younger women, but it was less
than for older women.*

   Seven particularly important published metaanalyses
provide assessments regarding the impact of breast
cancer screening, especially mammography shows a
modest benefit for women aged 40 to 49 years than for
women in their 50s and 60s(Reduction in Mortality 7-
24%(.**
                         * Smart CR, Hendrick RE, et al )2005(
                         **Humphrey LL, Helfand M, et al. (2006 )
Cervical Cancer Screening
               Statistical Data
► Cervical  carcinoma constitutes 3% of malignant
  tumors in Saudi Arabia.
► A worldwide steady 70% decline in mortality from
  cervical cancer has been observed since the mid-
  century after the introduction of widespread
  Papanicolaou (Pap) cytologic screening.
► Incidence and mortality are higher in women
  with.    No prior screening.
             Concurrent human papillomavirus (HPV) infection
             (the estimated absolute risk was more than 20% within 10
             years)*.

             Lower socioeconomic status.
                                          * Kiaer S,etal; Cancer Res. ;2006
Current USA Recommendations
  Annual screening should start approximately
3    years after the onset of sexual activity, at
least by age 21 years.

  Screening at Less frequent interval(2-
3years): After normal three consecutive annual
cervical   cytology   and   negative HPV    DNA
testing.

  Screening at 6 months interval: In high-risk
HPV DNA positive or risk of high-grade cervical
neoplasia (Colposcopy shoud be performed).
    Relation between age and cancer
            cervix screening

Adolescents and women in their 20s   Old women (above 60)


 High likelihood of regression of    Receded squamocolumnar
    early dysplastic lesions           junction of the cervix


       Overdiagnosis                 Pap testing is less sensitive


  Aggressive treatment, and               Lack of screening
unnecessary harm from ablative
     surgical procedures
        New strategies to improve sensitivity
                and specificity


Liquid-based cytologies   Visual screening     HPV DNA testing
(approved by the FDA)

  Comparisons of the multiple strategies now available, including
visual screening, conventional cytology, liquid-based cytology (new
technique), and HPV DNA testing, have found that either liquid-
based cytology or HPV DNA testing provides a better balance
between sensitivity and specificity for cervical intraepithelial
neoplasia 3+ than conventional methods.

 The improved sensitivity of these strategies must be balanced
against the increased cost
    Results of Cancer Cervix
           Screening

  In conclusion, evidence strongly
suggests a decrease in mortality
(around 70% decline in mortality) for
regular screening with Pap tests in
women who are sexually active or who
have reached age 18 y. The upper limit
at which such screening ceases to be
effective is unknown
        New strategies to improve sensitivity
                and specificity


Liquid-based cytologies   Visual screening     HPV DNA testing
(approved by the FDA)

  Comparisons of the multiple strategies now available, including
visual screening, conventional cytology, liquid-based cytology (new
technique), and HPV DNA testing, have found that either liquid-
based cytology or HPV DNA testing provides a better balance
between sensitivity and specificity for cervical intraepithelial
neoplasia 3+ than conventional methods.

 The improved sensitivity of these strategies must be balanced
against the increased cost
Colorectal Cancer Screening
           Statistical data
  In Saudi Arabia; colorectal cancer constitutes
11% of all malignant tumors in people above 40
years of age. It is considered the fourth cause of
cancer death in the Kingdom.
   In the United States; colorectal carcinoma is the
third leading cause of death from cancer in both
males and females. Approximately 57,100 deaths
were predicted for colon and rectum cancers
combined in 2003. More recent; an estimated
104,950 new cases of colon cancer and 40,340
cases of rectal cancer had been registered in
2005.
                Screening procedures

Fecal occult         Sigmoidoscopy          Colonoscopy             High-contrast
blood test                                                          barium enema
(FOBT)              Advantage:             Advantage:       Its
  Decreased 13-                            superior sensitivity     An     alternative
                    1-    Removal     of                            for     examining
year cumulative                            and specificity
                    cancer      or     a                            the entire colon
mortality    from   precancerous lesion
colorectal cancer                          Risks:                   and finds its
                    in a biopsied polyp,                            usefulness      in
by 33%              thus      combining    1   /1000    patients   situations      in
                    screening       and    experience               which individuals
                    treatment in one       perforation              cannot tolerate
   The       main
                    step.                  3 /1000 have major      endoscopic
limitation is its
limited             2-performed            hemorrhage               procedures
specificity.        infrequent       ,     1 - 3 in 10,000 die
                    perhaps every 5 to     as a result of the
                    10 years.              procedure.
            Newer detection techniques

Immunohistochemical
                                    Virtual colonoscopy
screening tests of stool
                                Uses CT of the prepared colon
   The         molecular     and avoids the invasiveness and
 detection    of    DNA      discomfort of conventional optical
 mutations    in     cells   colonoscopy showed that a three-
 exfoliated         from     dimensional endoluminal display.
 neoplasms in the stool
                               Achieve 93.8% sensitivity and
   Highly sensitive and      a specificity of 96.0% for polyps
 specific approach that is   at least 10 mm in diameter
 noninvasive and thus        compared to optical colonoscopy
 more acceptable to          on the same asymptomatic
 patients                    average-risk subjects*.
                                     *Lee SJ, J Gastroenterol. 2006
 Individual under screening are divided
           into two categories

   Average-risk individuals              High-risk individuals
   (General population)



History of curative-         Individuals with               Inflammatory
intent resection of       hereditary syndromes              bowel disease
 colorectal cancer                                          of significant
                                                               duration


        Adenomatous polyposis          Hamartomatous plyposis
U.S. Preventive Services Task Force
        Recommendations


Average-risk individuals        High-risk individuals

 Annual     FOBT     with     Begin surveillance at earlier
flexible   sigmoidoscopy    age      with      endoscopic
every 5 years for men       examination and biopsy 1-2
and women aged 50           years intervals.
years and over. All           Prophylactic      colectomy
positive tests should be    should be considered in the
followed up by either       presence      of    persistent
colonoscopy or double       dysplasia wih        extensive
contrast barium enema.      inflammatory bowel disease.
    Results of Colorectal Cancer
             Screening
    Screening decreased 13-year cumulative mortality from
colorectal cancer by 33% *.

     Pickhardt et al evaluated the performance characteristics
of CT virtual colonoscopy for screening in 1,233 average-risk
asymptomatic adults. The sensitivity of virtual colonoscopy for
adenomatous polyps was 93.8% for polyps at least 10 mm in
diameter, 93.9% for polyps at least 8 mm in diameter, and
88.7% for polyps at least 6 mm in diameter. The sensitivity of
optical colonoscopy for adenomatous polyps was 91.5%,
92.3%, and 87.5% for the three sizes of polyps,
respectively**.
                        *Mandel JS, et al: J US Natl Cancer Inst ;91:434, 2002
                       **Pickhardt AJ, et al: N Engl J Med 349:2191-2200, 2003
Prostate Cancer Screening
            Statistical data
 Allover the world , 8.6% of men above 50 years of
age were affected annually with cancer prostate.

 In Saudi Arabia, prostate cancer constitutes 5.3% of
all malignant tumors affecting men.

 Prostate cancer was found to be the most commonly
diagnosed cancer among men in the United States
and is the second leading cause of male cancer
deaths. It is estimated that in 2003; 220,900 new
cases of prostate cancer were identified, with 28,900
deaths.
        The main screening modalities

Digital rectal examination             Serum prostate-specific antigen
           (DRE)                                  (PSA)
 only one in three patients             Sensitivity of up to 80% to
with a positive DRE has                85% but with low specificity.
prostate cancer.
                                         Using age-specific PSA ranges
                                       may be a promising strategy for
                                       increasing PSA sensitivity
           Integration of DRE with
   determination of PSA levels and      For concentration more than 4
   the use of TRUS in selected cases   ng/dL)
   should improve prostate cancer
   detection                               Endorectal    (transrectal)
                                           ultrasonography (TRUS) is
                                           indicated.
           Nonrandomized Studies
Investig   Screening   Sample   Ages Sensitivity Specificity    Positive   Detectio
ation      Test         Size     (Y)      (%)         (%)      Predictiv    n Rate
                                                                e Value       (%)
                                                                   (%)
Babaian      TRUS       2425    55-       77         89          15          2.4
 et al.,
 1992                           70                                         (overall)
             PSA                          67         82          43

Catalona     DRE        6630    ≥50       55         45          21          3.2
 et al.,
 1994
Mettlin      DRE        2999    55–       39         96          NA          2.0
et al.,                         70
 1997       TRUS                          66         92
Picone       TRUS      1008     48-       81         95          NA
et al.,
 2006                           93
   Randomized Clinical Trials
  The American NCI-funded PLCO trial is a 16-year
randomized control study that began in 1993. It is accruing
74,000 men aged 60 to 74 years and has a design power of
90% to determine 20% reduction of prostate cancer
mortality (final results are expected in 2009).
  In a review of published data from five prospective trials,
treatment of localized disease was associated with a marked
decrease in prostate cancer deaths*. Thus, strong evidence
shows improved prognosis for screen-detected cases.

  The European Randomized Study of Screening for Prostate
Cancer, is being conducted in eight European countries with
men aged 55 to 74 years at entry; there are approximately
180,000 participants. Results from these trials are expected
in 2008.
                                   *Labrie F. Prostate 2006;43:215.
      American Cancer Society
        Recommendations
  PSA test and DRE should be offered annually,
beginning at age 50 years , to men who have a life
expectancy of at least 10 years.
  Men at high risk (African Americans and those with
a first-degree relative diagnosed with prostate
cancer) screening should be offered at an earlier age
(40-45 years old).
   Prior to testing, physicians should discuss with their
patients the potential benefits of early prostate
cancer detection so that patients can make an
informed decision about undergoing screening.
Lung Cancer Screening
  Currently, screening for lung
cancer among asymptomatic
individuals     at     elevated
risk due to smoking history or
occupational exposures is not
        recommended.
 The Mayo Lung Project trial demonstrated that
screening with either chest x-rays or chest x-rays
plus sputum cytology lowered the stage at
presentation and increased survival, but neither
approach had any effect on lung cancer mortality*.

  Low-dose CT scanning is a new and potentially
efficacious method for early detection of lung cancer.
studies of low-dose CT screening are ongoing , which
will take approximately 10 years to produce results**.

Question remains about the mortality impact and cost
effectiveness. ??

                              * Fontana RS, et al: J Occup Med 1986
                              **Henschke CI, et al: N Engl J Med. 2006.
  Latest Recommendation
    The lack of demonstrated benefit
for the older screening approaches
should not be misinterpreted as nihilism
about the early detection of patients
with lung cancer.

    Individuals at risk who present with
symptoms consistent with lung cancer
deserve appropriate evaluation.
Skin Cancer Screening
  The incidence of skin cancer has increased
worldwide. In the United States, the
incidence rate for melanoma has increased
approximately 4% per year since the early
1970s.
 The U.S. Preventive Services recommends a
skin examination, every 3 years, and more
frequently (e.g., annually) for persons at risk
(e.g., those who have a family or personal
history of skin cancer, clinical evidence of
precursor lesions, and increased exposure to
sunlight) .
 How to overcome people's
barriers to cancer screening
             ???
  physician recommendations are the most
important factor in motivating people to be
screened.
    Simple reminders and letters, delivered
in print or by telephone, can double or
triple the odds that people will attain
needed tests.

   Interventions often are needed at
several levels: individual, provider, and
health system.
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