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PSA Screening and Cancer Treatment

PSA Screening and Cancer Treatment. Douglas S. Scherr, M.D. Assistant Professor of Urology Clinical Director, Urologic Oncology Weill Medical College-Cornell University. Criteria of a Screening Program. The Disorder The Test The Treatment The Screening Program.

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PSA Screening and Cancer Treatment

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  1. PSA Screening and Cancer Treatment Douglas S. Scherr, M.D. Assistant Professor of Urology Clinical Director, Urologic Oncology Weill Medical College-Cornell University

  2. Criteria of a Screening Program • The Disorder • The Test • The Treatment • The Screening Program

  3. Criteria of a Screening Program • The Disorder -Prostate Cancer • The Test • The Treatment • The Screening Program

  4. U.S. Incidence and Mortality of Prostate Cancer Surveillance, Epidemiology and End Results (SEER) Data

  5. Prevalence of Prostate Cancer % Men With PIN Or CaP Decade Sakr et al., J Urol, 150: 379, 1993

  6. Criteria of a Screening Test The Disorder “Prostate Cancer” • Natural history understood:-To die of prostate cancer or die with prostate cancer? -Conservative Treatment: a.) Gleason 2-4: 4-7% chance of death b.) Gleason 6: 18-30% chance of death c.) Gleason 8-10: 60-80% chance of death** Frankel et al. Lancet, 361: 1122, March 2003 **Albertsen et al., JAMA, 280: 975, 1998

  7. Lifetime Risk of Developing or Dying of Prostate Cancer for a 50-Year-Old Man in the United States Risk Proportional Lifetime Risk of Risk Ratio Risk Developing histologic cancer 42 % 11.7 100 Developing clinical cancer 16 % 4 38 Dying of prostate cancer 3.6 % 1 8.6 Modified from Scardino PT. Urol Clin N Am 1989 and Hum Path 1992; and from CA Cancer J Clin Jan-Feb, 2000.

  8. Criteria of a Screening Program • The Disorder • The Test • The Treatment • The Screening Program

  9. Criteria of a Screening TestThe Test • Simple, safe and precise • Distribution in target population should be known • Appropriate cut-offs and age defined ranges • Test should be acceptable to the populationDiagnostic tests performed when a positive test is found should be agreed upon

  10. Criteria of a Screening TestThe Test“DRE and PSA” Bangma et al., Urology, 46(6): 773, 1995

  11. Rate of Detection of Prostate Cancer by Needle Biopsy Positive Predictive Value of DRE and PSA (n=6630) PSA (ng/ml) 0-22-44-10>10 DRE- 1% 15% 25% >50% DRE+ 5% 20% 45% >75% Modified from Catalona et al: J Urol 1994: 151:1283.

  12. Positive Predictive Value of PSA and DRE for Prostate Cancer 46.6 31.6 25.5 24.6 23.2 14.6

  13. PREDICTIVE MODELING TABLES TO CALCULATE RISK OF POSITIVE BIOPSY BASED ON DRE, PSA, F/T PSA RATIO AND PSA DENSITY IN MEN WITH PSA < 10 NG/ML Tewari, Boorjan, Bartsch, 2005 PSA density should be calculated by ultrasound. A new model will be available soon if PSA density is not available)

  14. Serum PSA Levels Rise Prior to the Development of Significant Cancer From Carter HB et al. JAMA 267:2215,1992

  15. Criteria of a Screening TestThe Test“DRE and PSA”AUA Best Practice Policy • PSA detects more tumors than does DRE and it detects them earlier • Most Sensitive method uses both DRE and PSA PSA Best Practice Policy, Oncology, 14(2), Feb. 2000

  16. Factors That Affect PSA • Prostatitis • Benign Prostatic Hyperplasia (BPH) • Prostate Cancer • Physical Activity • Infection • Medications – finasteride (Proscar/Propecia) • Herbal Medicines – Saw Palmetto, PC-SPES, • Ejaculation • Rectal Examination • Urinary Retention/Cystoscopy

  17. Sensitivity/Specificity of PSA • Sensitivity: 67.5-80% (20-30% tumors will be missed if PSA<4.0 ng/ml used)Ways to Improve Sensitivity: a.) age-adjusted PSA b.) PSA velocity • Specificity: 60-70% (if PSA>4.0 ng/ml)(only ¼ prostate biopsies reveal CaP)Ways to Improve Specificity:a.) Age adjustment b.) Free-to-total PSA c.) PSA density

  18. Improvements on PSA • Age-adjusted PSA • Free-to-Total PSA(14-28%) • PSA Velocity (>0.75ng/ml/yr)

  19. Criteria of a Screening Program • The Disorder • The Test • The Treatment • The Screening Program

  20. Criteria of a Screening Test“The Treatment” • Watchful Waiting • Hormonal Deprivation Therapy • Radiation Therapy • Radical Prostatectomy

  21. Criteria of a Screening Program • The Disorder • The Test • The Treatment • The Screening Program

  22. Policies of Prostate Cancer Screening

  23. Evidence for the Effectiveness of Screening • PSA screening initiated in 1989 • A decrease in prostate cancer mortality has been demonstrated in the U.S. by 4.4%/year from 1994-97 • Total decrease in mortality of 17.6%

  24. Cost per annual adjusted life year for annual Prostate cancer screening Howard. J Health Econ., 24(5): 891-906, Sept. 2005

  25. Practice Patterns of General Practitioner Howard. J Health Econ., 24(5): 891-906, Sept. 2005

  26. Practice Patterns Amongst General Practitioners Jonler et al., Scan J Uol Nephol, 39: 214-218, 2005

  27. Side effects of screeningFlip side: Screening cause harmImpact of treatment on overall survival Gain in LE (Mo) Myocardial revascularization 1 vessel 7 2 vessels 0-8 3 vessels 4-14 Heart Transplantation 31-99 Cholecystectomy 2-3 Appendectomy 2-31 Treatment of prostate cancer (Fleming)1-11 Gl 5-7 30-60 Gl 8-10 Wright & Weinstein NEJM 1998:339:380-6

  28. Controversies in Screening • Decline in mortality since 1989 is too rapid given the indolent natural history of prostate cancer • Improvements in locally advanced disease could explain decline in mortality • Decline in mortality has been seen in countries where screening is not prevalent

  29. Quebec City Screening Study

  30. Quebec City Screening Study • November 1988-Decmeber 1996 • 46,193 men randomized screening vs. non-screening • Screening Group: 8,137 were screened • Relative risk of dying of CaP was 3.7 times higher in the control group • 69% reduction in mortality with screening Labrie et al., Prostate, 38(2): 83-91, 1999

  31. Tyrol Prostate Cancer Screening Group • 1993-1998, PSA screening offered to 65,123 men in Tyrol, Austria • 42% reduction in prostate cancer mortality Mortality Rates Bartsch et al., Urology, 58(3): 417-24, 2001 Incidence by Stage

  32. Olmstead County Screening Trial • Retrospective analysis of death record between 1980-1997 • Decline in mortality of 22% between the earliest and most recent time periods Trends in Prostate Cancer Mortality Roberts et al., J Urol, 161: 529, 1999

  33. Cost Effectiveness of PSA Screening Thompson et al., Oncology, 9: 141-5, 1995

  34. Problems with Screening Lead Time Bias Length Time Bias Thompson, Recent Advances in Prostate Cancer

  35. Breast Cancer vs. Prostate Cancer 1998 PROSTATE CA BREAST CA New Cases/Yr. 184,500 180,300 Deaths/Yr. 39,200 43,900 Deaths/Cases 21% 24% Lifetime risk of Developing 17% 14% Mets at Diagnosis 9% 6% Mortality Rate Trend (22 yr.) + 17% - 3% 5 Yr. Relative Survival Rate 93% 85% Median Age at Diagnosis 71 yr 64 yr Median Age at Death 77 yr 68 yr Scardino, MSKCC

  36. Ongoing Randomized Screening Trials • Prostate, Lung, Colon and Ovarian (PLCO) Trial of the NCIQ: Does screening decrease mortality? • European Randomized Study of Screening for Prostate Cancer (ERSPC)Q:Difference in CaP mortality in screened vs. unscreened patients?Q: Quality of life differences in screened population? • Prostate Cancer Intervention Vs. Observation Trial (PIVOT)Q: Does early, aggressive treatment decrease mortality? • Prostate Cancer Prevention Trial (PCPT)Q: Can finasteride prevent prostate cancer?

  37. Prostate, Lung, Colorectal and Ovarian (PLCO) Trial Men (74,000) and women (74,000) ages 55 to 74 years will be randomized to a control arm (routine medical care) or a screening arm which includes: • Prostate: PSA and DRE • Lung: CXR • Colorectal: Flexible sigmoidoscopy • Ovarian: Pelvic exam, CA125, Transvaginal ultrasound

  38. ERSPC Trial • Large, International cooperative study initiated in 1994 • Goal is to compare prostate cancer mortality between screened and control arms • With 165,000 men age 55-69 with a 20% contamination rate, the trial will reach a power of 86% to show a 20-25% mortality reduction • Results expected in 2008

  39. ERSPC Trial

  40. Impact of PSA on Survival Tsodikov et al. UC Davis

  41. What Can We Do While we Await the Results? • Improve diagnostics: 1.) Imaging 2.) More sensitive PSA • Improve Treatment Stratification: 1.) Nomograms • Improve Surgical Technique (lower morbidity) 1.) nerve sparing 2.) nerve grafts 3.) Laparoscopic Prostatectomy

  42. Improved Cancer Detection Through ImagingEndorectal MRI/Spectroscopy • Potential improvement over ultrasound • Biochemical gradients to decipher cancer from benign • Remains investigational • Possible role in high risk patients

  43. MRN 309468 Endo-rectal coil MRI

  44. * * * Image 8 I 54.44 mm Image 9 I 57.56 mm H H H H H H H H H H H H H H H H H H vc sc vc H H H H H H H H

  45. Treatment Stratifications • Allow for improvement in patient understanding • More objective in guiding treatment decisions • Less physician bias

  46. Preoperative Nomogram for Prostate Cancer Recurrence 0 10 20 30 40 50 60 70 80 90 100 Points PSA 4 20 0.1 1 2 3 6 7 8 9 10 12 16 30 45 70 110 T2a T2c T3a ClinicalStage T1c T1ab T2b  2+3  4+ 3+  2 Biopsy Gleason Grade  2+  2 3+3  3+ 4 Total Points 0 20 40 60 80 100 120 140 160 180 200 60MonthRec. Free Prob. .96 .93 .9 .85 .8 .7 .6 .5 .4 .3 .2 .1 .05 Instructions for Physician: Locate the patient’s PSA on the PSA axis. Draw a line straight upwards to the Points axis to determine how many points towards recurrence the patient receives for his PSA. Repeat this process for the Clinical Stage and Biopsy Gleason Sum axes, each time drawing straight upward to the Points axis. Sum the points achieved for each predictor and locate this sum on the Total Points axis. Draw a line straight down to find the patient’s probability of remaining recurrence free for 60 months assuming he does not die of another cause first. Note: This nomogram is not applicable to a man who is not otherwise a candidate for radical prostatectomy. You can use this only on a man who has already selected radical prostatectomy as treatment for his prostate cancer. Instruction to Patient: “Mr. X, if we had 100 men exactly like you, we would expect between <predicted percentage from nomogram - 10%> and <predicted percentage + 10%> to remain free of their disease at 5 years following radical prostatectomy, and recurrence after 5 years is very rare.” • 1997 Michael W. Kattan and Peter T. Scardino Kattan MW et al: JNCI 1998; 90:766-771.

  47. 50 10 T3c T2c 3 5 2 4 6 3D Conformal Radiation Therapy Nomogram for PSA Recurrence

  48. Palm Pilot Nomogram Software • Includes pretreatment and postoperative predictions. • Uses published nomograms in prostate cancer.

  49. Postoperative Nomogram for Prostate Cancer Recurrence 10 3, •  1998 Michael W. Kattan and Peter T. Scardino

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