2. Per-Anders Abrahamsson, Department of Urology Malmö University Hospital Sweden EAU, Berlin, March 24, 2007 What´s New in Prostate Cancer?

3. Global incidence of prostate cancer * <7.4 <13.8 <24.5 <40.7 <124.8 *Age-standardised incidence rates per 100,000GLOBOCAN 2002

4. Mortality in different countries 1992 - 1995 Japan Russia Greece Mexico Italy Israel Spain France Canada Germany England Austria USA Finland Irland Netherlands Australia New Zealand Denmark Schwitzerland Norway Landis et al 1998 Mortality per 100,000 men Sweden

5. Prostate-Specific Antigen l Best cancer marker ever discovered l Used for: Detection and screening Prognosis & Monitoring of prostate cancer

6. The Ultimate Goal of Early Detection for Prostate Cancer PIN Organ- confined Locallyadvanced N+ M+ Vol. (ml) 1 4 25 100 1000 PSA (ng/ml) 3 10 20 200 300 700 Window of curability

7. Is PSA still useful ?

8. Prostate Cancer Prostate Cancer 2 mm 3 urethra 15 mm 3 1991 2006

9. Reality of PSA Testing HEALTHY & BENIGN DISEASE PROSTATE CANCER CUT OFF 70% FALSE POS. PSA Ng/mL 0.01.02.03.04.05.06.07.08.09.010.0100.0 20% FALSE NEG.

10. PSA and Prostate Cancer PSANumberCancerHG Cancer < 0.54866.6%0.83% 0.6-1.079110.1%1% 1.1-2.099817%2.1% 2.1-3.048223.9%4.6% 3.1-4.019326.9%6.7% Total295015.2%2.26% Thompson IM et al. N Engl J Med 2004;350:2239-46

11. The Problem Normal / BPH Prostate cancer Potentially Lethal prostate cancer IDEAL SCREENING TEST

12. European Randomized Study of Screening for Prostate Cancer (ERSPC) ScreenControl Number21,14521,132 Prostate Cancer1190189 Incidence21.53.1 Ratio incidence6.511 Ratio incidence/mortality 14.82.25 “Overdiagnosis” remains a concern; Schröder F, WHO, 2004

13. Andriole GL. J Natl Cancer Inst. 2005;97:433-8. Gleason score % of screening-detected prostate cancer 2–42–410% 5–65–645% 731% 8–1012% Most screening-detected prostate cancers are less aggressive Early Detection/Screening

14. PSA era is not over: We should use PSA better! PSA provides a continuum of risk assessment l Do not focus only on total PSA cutoff l Repeat PSA measurement and rule out prostatitis l Use PSA velocity or doubling time, and l % free and % complexed PSA, proPSA Catalona, J Urol, 2005

15. How to Predict Development of Prostate Cancer on an Individual Basis Can Plasma levels of PSA predict long-term risk for Prostate Cancer ?

16. Risk for Prostatate Cancer Diagnosis in Men < 53 years at Blood Sampling and with follow up  13 to 25 years 7.4-30.5 14.9 >  3.0 7.4-26.2 13.9 2.0-  3.0 4.9-14.5 8.4 1.5-<2.0 2.1-5.0 3.2 1.0-<1.5 1.4-2.9 2.0 0.5-<1.0 1 < 0.5 95% CI interval Odds ratioPSA range Lilja, Abrahamsson et al., J Clin Onc; 2007

17. Screening Scenario l How avoid overtreatment: 1. Use of the long therapeutic window to guide treatment 2. PSA kinetics: PSA Doubling Time or PSA Velocity as a guide to intervention

18. The take-home-messages - PSA Kinetics - Simple, inexpensive and readily available Should be incorporated into patient risk assessment ! Should be incorporated into patient risk assessment !

19. DD3  2M 6547981231011121314 15 Pr 17M PCA3 DD3 is the most prostate-cancer- specific gene described to date Over-expressed in >95% of PC Expression restricted to the prostate

20. Digital Rectal Exam (DRE) Cells in prostatic urethra