Prevention with FinasteridePrevention with Finasteride

Ian M. Thompson, MD

October, 2009

F/U q3mo x 7yrAnnual DRE & PSA

Biopsy for cause

End of Study Biopsy

End of Study Biopsy

Enrollment

Placebo Finasteride

Randomization

The Prostate Cancer Prevention TrialThe Prostate Cancer Prevention Trial

PlaceboPlacebo

0 z 4.00 z 4.0

Finasteride PlaceboFinasteride Placebo Index IndexIndex Index

FinasterideFinasteride

X%X%

X%X%

PSA IndexPSA Index

PSAPSA(ng/ml)(ng/ml)

Total Number of Cancers Total Number of Cancers by Gleason Scoreby Gleason Score

803

20

457

19090

1147

55

776

18453

0100200300400500600700800900

100011001200

TotalCancers

2 - 4 5 - 6 7 8 - 10

Gleason Score

Num

ber o

f Can

cers

Finasteride = 4368Placebo - 4692

25% Risk Reduction Thompson et al, NEJM 349:215, 2003

Concerns Regarding PCPTConcerns Regarding PCPT

803

20

457

19090

1147

55

776

18453

0100200300400500600700800900

100011001200

TotalCancers

2 - 4 5 - 6 7 8 - 10

Gleason Score

Num

ber o

f Can

cers

Finasteride = 4368Placebo - 4692

It now appears that increased sensitivity of detection may have

led to increase in HG tumorsFinasteride:- Increases ability of PSA to detect

cancer and aggressive cancer.- Increases ability of DRE to detect

cancer- Improves ability of prostate biopsy to

detect cancer and to detect aggressive cancer.

AUC finasteride = 0.757AUC placebo = 0.681p<.001

PlaceboFinasteride

Thompson JNCI 2006;98:1128

AUC finasteride = 0.886AUC placebo = 0.824

Placebo

Finasteride

Thompson JNCI 2006;98:1128

Finasteride improves sensitivity of PSA

PSAPlacebo

PSAFinasteride Specificity Sensitivity

PlaceboSensitivityFinasteride

Cancer vs. No Cancer4.1 1.6 92.7% 24% 37.8% Gleason >7 versus other4.1 1.6 90.5% 39.2% 53%

Journal of the National Cancer Institute, 2006;98

Sensitivity Finasteride Placebo p-valueOutcome Prostate CA 21.3% 16.7% 0.013Gleason > 7 26.1% 21.7% 0.25Gleason > 8 38.3% 36.4% 0.86

No decrease in specificity with finasteride.

Journal of Urology 2007;177:1749-52.

Finasteride improves sensitivity of DRE

Impact of smaller prostate on sensitivity of biopsy for HG

disease

0

20

40

60

80

100

Finasteride Placebo

% H

G c

ance

rs fo

und

at b

iops

y

50%

70%

p = .01

Redman Modeling of Actual Cancer rates

CancerRR=0.70 (0.64, 0.76)p < .0001

Gleason ≤ 6RR=0.68 (0.57, 0.82)p < .0001

Gleason ≥ 7RR=0.72 (0.55, 0.94)p < .020%

5%

10%

15%

20%

25%

Placebo Finasteride

High gradeLow grade

8.2%

6.0%

8.7%12.9%

Conclusions

• Finasteride significantly reduces risk of cancer.

• High grade cancer detection may be increased through improved biomarkers and biopsy. (could be additional benefit)

• Relative risk reduction - > 25%

• Absolute risk reduction – depends on definition. As great as 7%, as low as 2%.