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

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

3. 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 United States Preventive Services Task Force (USPSTF)American Medical Association (AMA)American College of Physicians (ACP)American Academy of Family Practitioners (AAFP)American College of Cardiology (ACC)American Heart Association (AHA)American Cancer Society (ACS)American Diabetes Association (ADA) United States Preventive Services Task Force (USPSTF)American Medical Association (AMA)American College of Physicians (ACP)American Academy of Family Practitioners (AAFP)American College of Cardiology (ACC)American Heart Association (AHA)American Cancer Society (ACS)American Diabetes Association (ADA)

4. 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 United States Preventive Services Task Force (USPSTF)American Medical Association (AMA)American College of Physicians (ACP)American Academy of Family Practitioners (AAFP)American College of Cardiology (ACC)American Heart Association (AHA)American Cancer Society (ACS)American Diabetes Association (ADA) United States Preventive Services Task Force (USPSTF)American Medical Association (AMA)American College of Physicians (ACP)American Academy of Family Practitioners (AAFP)American College of Cardiology (ACC)American Heart Association (AHA)American Cancer Society (ACS)American Diabetes Association (ADA)

5. 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 United States Preventive Services Task Force (USPSTF)American Medical Association (AMA)American College of Physicians (ACP)American Academy of Family Practitioners (AAFP)American College of Cardiology (ACC)American Heart Association (AHA)American Cancer Society (ACS)American Diabetes Association (ADA) United States Preventive Services Task Force (USPSTF)American Medical Association (AMA)American College of Physicians (ACP)American Academy of Family Practitioners (AAFP)American College of Cardiology (ACC)American Heart Association (AHA)American Cancer Society (ACS)American Diabetes Association (ADA)

6. USPSTF Guidelines 2005 Good: Evidence includes consistent results from well designed, well-conducted studies in representative populations that directly assess effects on health outcomes. Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes. Poor: Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.Good: Evidence includes consistent results from well designed, well-conducted studies in representative populations that directly assess effects on health outcomes. Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes. Poor: Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.

7. USPSTF Guidelines 2005 GRADE A Strongly recommends Good evidence GRADE B Recommends Fair evidence GRADE A The USPSTF strongly recommends that clinicians provide [the service] to eligible patients. The USPSTF found GOOD EVIDENCE that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms. GRADE B The USPSTF recommends that clinicians provide [the service] to eligible patients. The USPSTF found at least FAIR EVIDENCE that [the service] improves important health outcomes and concludes that benefits outweigh harms. GRADE A The USPSTF strongly recommends that clinicians provide [the service] to eligible patients. The USPSTF found GOOD EVIDENCE that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms. GRADE B The USPSTF recommends that clinicians provide [the service] to eligible patients. The USPSTF found at least FAIR EVIDENCE that [the service] improves important health outcomes and concludes that benefits outweigh harms.

8. 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. GRADE C The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least FAIR EVIDENCE that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation. GRADE D The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least FAIR EVIDENCE that [the service] is ineffective or that harms outweigh benefits. GRADE C The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least FAIR EVIDENCE that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation. GRADE D The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least FAIR EVIDENCE that [the service] is ineffective or that harms outweigh benefits.

9. 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 GRADE I The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that [the service] is effective is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. GRADE I The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that [the service] is effective is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

10. 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 Aspirin: Discuss aspirin chemoprevention with adults who are at increased risk for coronary heart disease. Address the potential benefits and harms of aspirin therapy. Bacteruria: Screen all pregnant women, using urine culture, at 12-16 weeks� Gestation Cervical Cancer: Screen women who have been sexually active and have a cervix Colorectal Cancer, Screening. Screen men and women 50 years of age or older. Hepatitis B Virus Infection, Screening. Screen pregnant women at their first prenatal visit. Aspirin: Discuss aspirin chemoprevention with adults who are at increased risk for coronary heart disease. Address the potential benefits and harms of aspirin therapy. Bacteruria: Screen all pregnant women, using urine culture, at 12-16 weeks� Gestation Cervical Cancer: Screen women who have been sexually active and have a cervix Colorectal Cancer, Screening. Screen men and women 50 years of age or older. Hepatitis B Virus Infection, Screening. Screen pregnant women at their first prenatal visit.

11. 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 High Blood Pressure, Screening. Screen adults 18 years of age and older. Lipid Disorders in Adults, Screening. Routinely screen men 35 years of age and older and women 45 years of age and older. Treat abnormal lipids in people at increased risk for coronary heart disease. Syphilis Infection, Screening. Screen persons at increased risk and all pregnant women. Tobacco Use and Tobacco-Caused Disease, Counseling to Prevent. Screen all adults and provide tobacco cessation interventions for those who use tobacco products. Screen all pregnant women and provide augmented pregnancy-tailored counseling to those who smoke. High Blood Pressure, Screening. Screen adults 18 years of age and older. Lipid Disorders in Adults, Screening. Routinely screen men 35 years of age and older and women 45 years of age and older. Treat abnormal lipids in people at increased risk for coronary heart disease. Syphilis Infection, Screening. Screen persons at increased risk and all pregnant women. Tobacco Use and Tobacco-Caused Disease, Counseling to Prevent. Screen all adults and provide tobacco cessation interventions for those who use tobacco products. Screen all pregnant women and provide augmented pregnancy-tailored counseling to those who smoke.

12. 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 Alcohol Misuse, Screening and Behavioral Counseling Interventions in Primary Care to Reduce. Use screening and behavioral counseling to reduce alcohol misuse by adults, including pregnant women. Breast Cancer, Chemoprevention. Discuss with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention. Inform patients of the potential benefits and harms. �B� Recommendation. (P. 17) Breast Cancer, Screening. Screening mammography, with or without clinical breast examination, every 1-2 years for women 40 years of age and older. �B� Recommendation. (P. 23) Breastfeeding, Behavioral Interventions to Promote. Recommend structured breastfeeding education and behavioral counseling programs. �B� Recommendation. Alcohol Misuse, Screening and Behavioral Counseling Interventions in Primary Care to Reduce. Use screening and behavioral counseling to reduce alcohol misuse by adults, including pregnant women. Breast Cancer, Chemoprevention. Discuss with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention. Inform patients of the potential benefits and harms. �B� Recommendation. (P. 17) Breast Cancer, Screening. Screening mammography, with or without clinical breast examination, every 1-2 years for women 40 years of age and older. �B� Recommendation. (P. 23) Breastfeeding, Behavioral Interventions to Promote. Recommend structured breastfeeding education and behavioral counseling programs. �B� Recommendation.

13. 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. Chlamydial Infection, Screening. Routinely screen all sexually active women 25 years of age and younger, and other asymptomatic women at increased risk for infection. �A� Recommendation. Routinely screen all asymptomatic pregnant women 25 years of age and younger and others at increased risk. Dental Caries in Preschool Children, Prevention. Primary care clinicians should prescribe oral fluoride supplementation at currently recommended doses to preschool children older than 6 months of age whose primary water source is deficient in fluoride Depression, Screening. Screen adults in clinical practices that have systems in place to assure accurate diagnosis, effective treatment, and follow-up. Chlamydial Infection, Screening. Routinely screen all sexually active women 25 years of age and younger, and other asymptomatic women at increased risk for infection. �A� Recommendation. Routinely screen all asymptomatic pregnant women 25 years of age and younger and others at increased risk. Dental Caries in Preschool Children, Prevention. Primary care clinicians should prescribe oral fluoride supplementation at currently recommended doses to preschool children older than 6 months of age whose primary water source is deficient in fluoride Depression, Screening. Screen adults in clinical practices that have systems in place to assure accurate diagnosis, effective treatment, and follow-up.

14. 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 Diet, Behavioral Counseling in Primary Care to Promote a Healthy. Intensive behavioral dietary counseling for adult patients with hyperlipidemia and other known risk factors for cardiovascular and dietrelatedchronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians. Routinely screen younger adults Recommended Preventive Services (men 20 to 35 years of age and women 20 to 45 years of age) if they have other risk factors for coronary heart disease. �B� Recommendation. Include measurement of total cholesterol and high density lipoprotein Cholestereol. Osteoporosis in Postmenopausal Women, Screening. Routinely screen women 65 years of age and older. Begin at age 60 for women at increased risk for osteoporotic fractures. �B� Recommendation. (P. 135) Rh (D) Incompatibility, Screening. Perform Rh (D) blood typing and antibody testing for all pregnant women during their first visit for pregnancy-related care. �A� Recommendation. Repeated Rh (D) antibody testing for all unsensitized Rh (D)-negative women at 24-28 weeks� gestation, unless the biological father is known to be Rh (D)-negative. Visual Impairment in Children Younger Than Age 5 Years, Screening. Screen to detect amblyopia, strabismus, and defects in visual acuity.Diet, Behavioral Counseling in Primary Care to Promote a Healthy. Intensive behavioral dietary counseling for adult patients with hyperlipidemia and other known risk factors for cardiovascular and dietrelatedchronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians. Routinely screen younger adults Recommended Preventive Services (men 20 to 35 years of age and women 20 to 45 years of age) if they have other risk factors for coronary heart disease. �B� Recommendation. Include measurement of total cholesterol and high density lipoprotein Cholestereol. Osteoporosis in Postmenopausal Women, Screening. Routinely screen women 65 years of age and older. Begin at age 60 for women at increased risk for osteoporotic fractures. �B� Recommendation. (P. 135) Rh (D) Incompatibility, Screening. Perform Rh (D) blood typing and antibody testing for all pregnant women during their first visit for pregnancy-related care. �A� Recommendation. Repeated Rh (D) antibody testing for all unsensitized Rh (D)-negative women at 24-28 weeks� gestation, unless the biological father is known to be Rh (D)-negative. Visual Impairment in Children Younger Than Age 5 Years, Screening. Screen to detect amblyopia, strabismus, and defects in visual acuity.

16. 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) Diet, Behavioral Counseling in Primary Care to Promote a Healthy. Intensive behavioral dietary counseling for adult patients with hyperlipidemia and other known risk factors for cardiovascular and dietrelatedchronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians. Routinely screen younger adults Recommended Preventive Services (men 20 to 35 years of age and women 20 to 45 years of age) if they have other risk factors for coronary heart disease. �B� Recommendation. Include measurement of total cholesterol and high density lipoprotein Cholestereol. Osteoporosis in Postmenopausal Women, Screening. Routinely screen women 65 years of age and older. Begin at age 60 for women at increased risk for osteoporotic fractures. �B� Recommendation. (P. 135) Rh (D) Incompatibility, Screening. Perform Rh (D) blood typing and antibody testing for all pregnant women during their first visit for pregnancy-related care. �A� Recommendation. Repeated Rh (D) antibody testing for all unsensitized Rh (D)-negative women at 24-28 weeks� gestation, unless the biological father is known to be Rh (D)-negative. Visual Impairment in Children Younger Than Age 5 Years, Screening. Screen to detect amblyopia, strabismus, and defects in visual acuity.Diet, Behavioral Counseling in Primary Care to Promote a Healthy. Intensive behavioral dietary counseling for adult patients with hyperlipidemia and other known risk factors for cardiovascular and dietrelatedchronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians. Routinely screen younger adults Recommended Preventive Services (men 20 to 35 years of age and women 20 to 45 years of age) if they have other risk factors for coronary heart disease. �B� Recommendation. Include measurement of total cholesterol and high density lipoprotein Cholestereol. Osteoporosis in Postmenopausal Women, Screening. Routinely screen women 65 years of age and older. Begin at age 60 for women at increased risk for osteoporotic fractures. �B� Recommendation. (P. 135) Rh (D) Incompatibility, Screening. Perform Rh (D) blood typing and antibody testing for all pregnant women during their first visit for pregnancy-related care. �A� Recommendation. Repeated Rh (D) antibody testing for all unsensitized Rh (D)-negative women at 24-28 weeks� gestation, unless the biological father is known to be Rh (D)-negative. Visual Impairment in Children Younger Than Age 5 Years, Screening. Screen to detect amblyopia, strabismus, and defects in visual acuity.

17. 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 the evidence is insufficient to recommend for or against routine screening for prostate cancer using prostate specific antigen (PSA) testing or digital rectal examinationthe evidence is insufficient to recommend for or against routine screening for prostate cancer using prostate specific antigen (PSA) testing or digital rectal examination

18. 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) < 10 y ACS PSA / DRE annually to 50-70 years or older than 45 with LE > 10 AUA PSA / DRE to 50-70 years or older than 45 with LE > 10; 40 to 50 years with family history/ African-American ethnicity with LE > 10 years the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

19. ? Conclusive Evidence the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

20. Prostate Cancer Guidelines Developed Prior To Thompson et. al. JAMA 2005 Jul 6;294(1):66-70 Await results of PLCO trial Journal Club the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

21. Thank You the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

22. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

23. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

24. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

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

26. 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 6;294(1):66-70.

27. Methods Prostate Cancer Prevention Trial 1991 to 2003, Multi-Center: 221 N = 18 882 Men 55 years and older Normal DRE and PSA < 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 > 4.0 End of study 7 yrs the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

28. Methods Central laboratory: PSA Sensitivity, Specificity for various cutoffs Receiver operating characteristic curve (ROC) Prostate Ca. vs no Prostate Ca Gleason Grade > = 7 vs. rest Gleason Grade > = 8 vs. rest Null Hypothesis: Area under ROC = 50 % Adjustment for participants without biopsy Mathematical modeling the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

29. 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 < = 4.0 Negative DRE the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

30. RESULTS PSA cutoff: 4.1 Sensitivity = 20.5 % 79.5% False Negative Rate > 79.5% Cancer Cases Missed Specificity = 93.8 % 6.2% False Positive Rate > 6.2 % potentially subjected to biopsy PSA cutoff: 2.6 Sensitivity = 40.5 % 59.5% False Negative Rate > 59.5% Cancer Cases Missed Specificity = 81.1 % 18.9% False Positive Rate > 18.9 % potentially subjected to biopsy the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

31. RESULTS PSA cutoff: 1.1 Sensitivity = 83.4 % 16.6% False Negative Rate > 16.6% Cancer Cases Missed Specificity = 38.9 % 61.1% False Positive Rate >61.1 % potentially subjected to biopsy ROC curve Any cancer vs. no cancer AUC = 0.678 (0.666-0.689) Statistically significant p < 0.001 the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

32. RESULTS Results Per Gleason Grade Higher grade cancers More sensitive Slightly less specific Higher AUC 0.0782, 0.827 Results Per Age (< 70 vs. rest) Higher AUC for those < 70 years Results Per Biopsy (ever vs. never) Nearly identical post statistical adjustment Results Per DRE (normal vs. abnormal) Difference not statistically significant the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

33. RESULTS the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

34. RESULTS the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

35. 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 the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

36. 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� the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

37. 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 the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

38. CRITICAL APPRAISAL External Validity (Generalizability) Healthy volunteers mean age = 62 yrs Compliant Low initial PSA values Discussion the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

39. 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 the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

40. 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 > = 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 > = 4.1 = 48% the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

41. DISCUSSION CASE PSA in 72 yr Gentleman with HTN, Hyperlipidemia, Ex Smoker with CAD Life expectancy probably > 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 the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.

42. Thank you the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. the PSA test and the [digital rectal examination] should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45.