What s New in Prostate Cancer Per-Anders Abrahamsson Department

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

Global incidence of prostate cancer* <7. 4 <13. 8 <24. 5 <40. 7 <124. 8 *Age-standardised incidence rates per 100, 000 GLOBOCAN 2002

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

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

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

Is PSA still useful ?

Prostate Cancer 2006 1991 urethra 2 mm 3 15 mm 3

Reality of PSA Testing HEALTHY & BENIGN DISEASE CUT OFF PROSTATE CANCER PSA Ng/m. L 0. 0 1. 0 2. 0 3. 0 4. 0 20% FALSE NEG. 5. 0 6. 0 7. 0 8. 0 70% FALSE POS. 9. 0 100. 0

PSA and Prostate Cancer PSA Number Cancer HG Cancer < 0. 5 486 6. 6% 0. 83% 0. 6 -1. 0 791 10. 1% 1% 1. 1 -2. 0 998 17% 2. 1 -3. 0 482 23. 9% 4. 6% 3. 1 -4. 0 193 26. 9% 6. 7% Total 2950 15. 2% 2. 26% Thompson IM et al. N Engl J Med 2004; 350: 2239 -46

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

European Randomized Study of Screening for Prostate Cancer (ERSPC) Screen Control Number 21, 145 21, 132 Prostate Cancer 1190 189 Incidence 21. 5 3. 1 Ratio incidence 6. 51 1 Ratio incidence/mortality 14. 8 2. 25 • “Overdiagnosis” remains a concern; Schröder F, WHO, 2004

Early Detection/Screening • Most screening-detected prostate cancers are less aggressive % of screening-detected Gleason score prostate cancer 2– 4 10% 5– 6 45% 7 31% 8– 10 12% Andriole GL. J Natl Cancer Inst. 2005; 97: 433 -8.

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, pro. PSA Catalona, J Urol, 2005

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

Risk for Prostatate Cancer Diagnosis in Men < 53 years at Blood Sampling and with follow up 13 to 25 years PSA range Odds ratio 95% CI interval < 0. 5 1 0. 5 -<1. 0 2. 0 1. 4 -2. 9 1. 0 -<1. 5 3. 2 2. 1 -5. 0 1. 5 -<2. 0 8. 4 4. 9 -14. 5 2. 0 - 3. 0 13. 9 7. 4 -26. 2 > 3. 0 14. 9 7. 4 -30. 5 Lilja, Abrahamsson et al. , J Clin Onc; 2007

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

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

• PCA 3 DD 3 is the most prostate-cancerspecific gene described to date • Over-expressed in >95% of PC • Expression restricted to the prostate 1 DD 3 2 M 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Pr 17 M

Cells in prostatic urethra Digital Rectal Exam (DRE)