Per-Anders Abrahamsson, Per-Anders Abrahamsson, Department of UrologyDepartment of Urology

Malmö University HospitalMalmö University HospitalSwedenSweden

EAU, Berlin, March 24, 2007EAU, Berlin, March 24, 2007

What´s New in Prostate Cancer?What´s New in Prostate Cancer?

Global incidence of Global incidence of prostate cancerprostate 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

0 5 10 15 20 25

JapanRussiaGreeceMexico

ItalyIsraelSpain

FranceCanada

GermanyEnglandAustria

USAFinland

IrlandNetherlands

AustraliaNew Zealand

Denmark

SchwitzerlandNorway

Landis et al 1998Mortality per 100,000 men

Sweden

Prostate-Specific AntigenProstate-Specific Antigen

Best cancer marker ever discovered

Used for:Detection and screeningPrognosis & Monitoring of prostate cancer

The Ultimate Goal of Early Detection The Ultimate Goal of Early Detection for Prostate Cancerfor Prostate Cancer

PINPIN

Organ-confinedOrgan-confined

LocallyLocally

advancedadvanced N+N+

M+M+

Vol. (ml) 1 4 25 100 1000Vol. (ml) 1 4 25 100 1000

PSA (ng/ml) 3 10 20 200 300 700PSA (ng/ml) 3 10 20 200 300 700

Window of curabilityWindow of curability

Is PSA still useful ?

Prostate CancerProstate Cancer

2 mm3

urethra urethra

15 mm3

1991199120062006

Reality of PSA TestingReality of PSA Testing

HEALTHY & BENIGN DISEASE

PROSTATE CANCER

CUT OFF

70%FALSE POS.

PSANg/mL0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 100.0

20%FALSE NEG.

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%

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

Andriole GL. J Natl Cancer Inst.

2005;97:433-8.

Gleason score

% of screening-detected prostate cancer

2–4 10%

5–6 45%

7 31%

8–10 12%

•Most screening-detected prostate

cancers are less aggressive

Early Detection/Screening

PSA era is not over:We should use PSA better!

PSA provides a continuum of risk assessment Do not focus only on total PSA cutoff Repeat PSA measurement and rule out prostatitis Use PSA velocity or doubling time, and % free and % complexed PSA, proPSA

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

7.4-30.514.9> 3.0

7.4-26.213.92.0- 3.0

4.9-14.58.41.5-<2.0

2.1-5.03.21.0-<1.5

1.4-2.92.00.5-<1.0

1< 0.5

95% CI interval

Odds ratioPSA range

Lilja, Abrahamsson et al., J Clin Onc; 2007

Screening Scenario

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

The take-home-messages

- PSA Kinetics -

• Simple, inexpensive and readily available

• Should be incorporated into patient Should be incorporated into patient risk risk assessment !assessment !

DD3

2M

654 7 981 2 3 10 11 12 13 14 15 Pr 17 M

• PCA3DD3 is the most prostate-cancer-specific gene described to date

• Over-expressed in >95% of PC

• Expression restricted to the prostate

Digital RectalExam (DRE)

Cells in prostaticurethra