Screening in the

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• Screening in the
• Primary Care Office
• Milan C. Mathew
• Resident in Internal Medicine
• Memorial Hospital of Rhode Island

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Definition

• Screening is a public health service in which
  members of a defined population, who do not
  necessarily perceive they are at risk of, or are
  already affected by a disease or its
  complications, are asked a question or offered a
  test, to identify those individuals who are more
  likely to be helped than harmed by further tests
  or treatment to reduce the risk of a disease or
  its complications.
• UK National Screening Committee

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Screening

• Disease Features
• Disease significantly impacts public health
• Detection occurs before a critical point
• Critical point occurs before clinical diagnosis
• Screened patient is still asymptomatic
• Diagnosis would not otherwise occur this early
• Critical point occurs in time to affect outcome
• Disease must be detected early enough for cure

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Screening

• Test Features
• High Sensitivity to detect asymptomatic disease
• High Specificity minimizes false positives
• Screening test tolerated by patients
• Screened Population Features
• Disease has high enough Prevalence
• Medical care available if screening test positive
  
• Patient willing to undergo further evaluation
• Costs balanced with benefit

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Screening

• Many Medical Organizations Many Guidelines
• Most Medical Organizations
• Literature review Expert Opinion
• Conflict Per Recommendation
• Primary Care Office
• United States Preventive Services Task Force
  (USPSTF) Guidelines
• Regularly updated
• Evidence based

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USPSTF Guidelines 2005
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USPSTF Guidelines 2005

• GRADE A
• Strongly recommends
• Good evidence
• GRADE B
• Recommends
• Fair evidence

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USPSTF Guidelines 2005

• GRADE C
• No recommendation
• Fair Evidence can improve health outcomes
• Balance of benefits and harms is too close
• GRADE D
• Recommends against
• Fair Evidence ineffective or that harms outweigh
  benefits.

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USPSTF Guidelines 2005

• GRADE I
• Insufficient
• Evidence that the service is effective is
  lacking, of poor quality, or conflicting, and the
  balance of benefits and harms cannot be
  determined.
• Recommended Services
• Includes Screening, Counseling and Preventive
  Medications
• Grade A
• Grade B

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Grade A

• Aspirin
• Primary Prevention of Cardiovascular Events
• Bacteriuria
• Asymptomatic pregnant women, Urine Culture, 12-16
  wks
• Cervical Cancer
• Sexually active, have cervix
• Colorectal Cancer
• 50 years and older
• Hepatitis B Virus Infection
• Pregnant women at first visit

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Grade A

• High Blood Pressure
• Adults over 18 years
• Lipid Disorders in Adults
• Men over 35, Women over 45
• Syphilis Infection
• Increased Risk
• All pregnant women
• Tobacco Use and Tobacco-Caused Disease Counseling
  
• All adults
• All pregnant women
• Augmented pregnancy tailored counseling

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Grade B

• Alcohol Misuse, Screening and Behavioral
  Counseling
• Adults
• Pregnant women
• Breast Cancer, Chemoprevention
• Breast Cancer, Screening
• Screening mammography, with or without clinical
  breast examination, every 1-2 years for women 40
  years of age and older
• Breastfeeding, Behavioral Interventions

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Grade B

• Chlamydial Infection
• Sexually active women 25 years of age and younger
• Asymptomatic women at increased risk
• Asymptomatic pregnant women 25 years younger and
  others at increased risk.
• Dental Caries in Preschool Children
• Oral fluoride supplementation to children older
  than 6 months whose water is deficient to
  fluoride
• Depression
• Adults
• Diabetes Mellitus in Adults, Screening for Type
  2.
• Screen adults with hypertension or hyperlipidemia.

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Grade B

• Diet, Behavioral Counseling
• Adults with Hyperlipidemia
• Risk factors for cardiovascular or diet related
  chronic disease
• Obesity in Adults
• Osteoporosis in Postmenopausal Women
• 65 years or older
• 60 or older for women at increased risk
• Rh (D) Incompatibility
• Visual Impairment in Children 5 Years and younger
• Amblyopia, strabismus, and defects in visual
  acuity

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Discussion Case

• 72 yr Gentleman with HTN, Hyperlipidemia, Ex
  Smoker with CAD
• Recommendations
• Grade A Grade B
• Aspirin (yes) AAA (no)
• Blood pressure (yes) Alcohol misuse (yes)
• Colorectal Cancer (yes) Dental Periodont
  (yes/no)
• HIV (no not at high risk) Depression (yes/no)
• Lipid Disorders (yes) Diabetes Mellitus (yes)
• Syphilis (no not at high risk) Diet (yes)
• Tobacco use (yes) Obesity (yes)
• TB infection (not at high risk)

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Prostate Cancer

• PSA / Digital Rectal Examination and Prostate Ca.
• USPSTF Recommendations
• Grade I (insufficient for or against)
• Benefit Unknown
• PSA more sensitive than DRE
• Yield decreases with repeated testing (biennial
  better)
• If ordering
• Discuss potential but uncertain benefits and
  possible harms
• Help patients understand the uncertainty and gaps
  in evidence

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Prostate Cancer

• ACP-ASIM / AAFP / AMA
• Discuss
• Benefits and Harms, Patient preferences,
  Individualize
• Benefit Likely (Consensus)
• Age group, 50-70 years
• Older than 45 if high risk (African-American and
  Family History)
• Benefit Unlikely (Consensus)
• Older men
• Men with other significant medical problems with
  life expectancy (LE) lt 10 y
• ACS
• PSA / DRE annually to 50-70 years or older than
  45 with LE gt 10
• AUA
• PSA / DRE to 50-70 years or older than 45 with LE
  gt 10
• 40 to 50 years with family history/
  African-American ethnicity with LE gt 10 years

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? Conclusive Evidence

• Prostate, Lung, Colorectal and Ovarian Cancer
  Screening trial
• National Cancer Institute
• N 154, 000 between 1992 and 2001
• Ages 55 -74, Multi-Center
• PSA (Annually 5 yrs), DRE (Annually 3 yrs)
• CXR (Smokers Annually 3 yrs, Non Sm. Annually 2
  yrs)
• Flexible sigmoidoscopy (Twice 2 yrs apart)
• CA-125 (Annually 5 yrs)
• Transvaginal USG (Annually 3 yrs)

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Prostate Cancer

• Guidelines Developed Prior To
• Thompson et. al. JAMA 2005 Jul 6294(1)66-70
• Await results of PLCO trial
• Journal Club

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• Thank You

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• Journal Club
• Milan C. Mathew
• Resident in Internal Medicine
• Memorial Hospital of Rhode Island

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• Operating Characteristics of
• Prostate-Specific Antigen in
• Men With an Initial PSA level
• of 3.9 ng/ml or lower
• Thompson et. al. JAMA 2005 Jul 6294(1)66-70.

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Methods

• Prostate Cancer Prevention Trial
• 1991 to 2003, Multi-Center 221
• N 18 882 Men 55 years and older
• Normal DRE and PSA lt or 3.0 ng/l
• Randomized Finasteride vs. Placebo, 7 yrs
• Annual DRE and PSA, 7 yrs
• Confirmatory Test 6 Core biopsy
• If DRE suspicious
• If PSA gt 4.0
• End of study 7 yrs

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Methods

• Central laboratory PSA
• Sensitivity, Specificity for various cutoffs
• Receiver operating characteristic curve (ROC)
• Prostate Ca. vs no Prostate Ca
• Gleason Grade gt 7 vs. rest
• Gleason Grade gt 8 vs. rest
• Null Hypothesis Area under ROC 50
• Adjustment for participants without biopsy
• Mathematical modeling

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RESULTS

• Placebo group 9459
• Number with PSA and DRE in same yr 8575 (Table
  1)
• Number with PSA, DRE and Biopsy in same yr 5587
  (65.2) Verified
• Number not verifiable 8575 5587 2988 No
  Biopsy
• Verifiable
• Older
• Positive family history
• Non-Verifiable
• PSA lt 4.0
• Negative DRE

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RESULTS

• PSA cutoff 4.1
• Sensitivity 20.5
• 79.5 False Negative Rate gt 79.5 Cancer Cases
  Missed
• Specificity 93.8
• 6.2 False Positive Rate gt 6.2 potentially
  subjected to biopsy
• PSA cutoff 2.6
• Sensitivity 40.5
• 59.5 False Negative Rate gt 59.5 Cancer Cases
  Missed
• Specificity 81.1
• 18.9 False Positive Rate gt 18.9 potentially
  subjected to biopsy

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RESULTS

• PSA cutoff 1.1
• Sensitivity 83.4
• 16.6 False Negative Rate gt 16.6 Cancer Cases
  Missed
• Specificity 38.9
• 61.1 False Positive Rate gt61.1 potentially
  subjected to biopsy
• ROC curve
• Any cancer vs. no cancer
• AUC 0.678 (0.666-0.689)
• Statistically significant p lt 0.001

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RESULTS

• Results Per Gleason Grade
• Higher grade cancers
• More sensitive
• Slightly less specific
• Higher AUC 0.0782, 0.827
• Results Per Age (lt 70 vs. rest)
• Higher AUC for those lt 70 years
• Results Per Biopsy (ever vs. never)
• Nearly identical post statistical adjustment
• Results Per DRE (normal vs. abnormal)
• Difference not statistically significant

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RESULTS
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RESULTS
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CONCLUSIONS

• No cutoff PSA
• High Sensitivity
• High Specificity
• Continuum of risk for all values
• AUC for ROC
• Statistically significant
• Not sufficient to discriminate those with/without
  disease
• Irrespective of Age or Severity

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HIGHLIGHTS

• Prostate Cancer
• Most Common Ca. in US men
• Second most common cause of cancer related
  mortality
• PSA screening very common
• 75, 50 yrs and older
• 54 regular PSA screening
• Prospective Biopsy irrespective of PSA (Only
  ONE!)
• Adjustment for Verification Bias
• Potentially explains
• Fall in Prostate Ca mortality irrespective of
  Screening Rates
• 35 risk of treatment post Radical Prostatectomy
  recurrence

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CRITICAL APPRAISAL

• Internal Validity
• Independent blind comparison with gold standard
  (biopsy)
• Not reported
• Not very concerned as results do not demonstrate
  benefit of PSA screening
• Was gold standard done on all patients
  irrespective of PSA
• Attempted
• 34.9 Not verified by biopsy
• Statistical adjustment/Mathematical modeling
• Screening bias
• Healthy patients with low overall mortality
• Lead time bias
• Early diagnosis falsely appears to increase
  survival without doing so.
• Length time bias
• Over representation of less aggressive disease
  which have better prognosis
• However Mortality Not Examined

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CRITICAL APPRAISAL

• External Validity (Generalizability)
• Healthy volunteers mean age 62 yrs
• Compliant
• Low initial PSA values
• Discussion

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POINTS TO PONDER

• Does early diagnosis
• Improved survival
• Improved quality of life
• Not known
• Will those screen be willing to take treatment
• Probable
• Is time, energy and costs of early diagnosis
  worth it
• Yes
• Is the target disorder frequent and severe
• Yes

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POINTS TO PONDER

• Ability of test to discriminate
• Sensitivity / Specificity/ Likelihood ratios (LR)
• LR
• PSA 4.1, LR 3.3
• PSA 2.1, LR 1.9
• PSA 1.1, LR 1.4
• Post Test Probability (PTP) for PSA gt 4.1
• Pre Test Probability 25 , PTP 53
• Pre Test Probability 50 , PTP 75
• Pre Test Probability 75 , PTP 90
• Positive Predictive Value for PSA gt 4.1 48

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DISCUSSION CASE

• PSA in 72 yr Gentleman with HTN, Hyperlipidemia,
  Ex Smoker with CAD
• Life expectancy probably gt 10 years
• Test or Not to Test
• Does the test add to anything I know about
  patient?
• What if high, what if low
• Willingness for biopsy?
• Await results of PLCO trial
• Discussion

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• Thank you