prevention with finasteride
DESCRIPTION
Prevention with Finasteride. Ian M. Thompson, MD October, 2009. The Prostate Cancer Prevention Trial. Enrollment. Randomization. Finasteride. Placebo. F/U q3mo x 7yr Annual DRE & PSA Biopsy for cause. End of Study Biopsy. End of Study Biopsy. PSA Index. X%. Placebo. X%. Finasteride. - PowerPoint PPT PresentationTRANSCRIPT
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
184
53
0
100200
300
400500
600
700800
900
10001100
1200
TotalCancers
2 - 4 5 - 6 7 8 - 10
Gleason Score
Nu
mb
er o
f C
ance
rs
Finasteride = 4368
Placebo - 4692
25% Risk Reduction Thompson et al, NEJM 349:215, 2003
Concerns Regarding PCPTConcerns Regarding PCPT
803
20
457
19090
1147
55
776
184
53
0
100200
300
400500
600
700800
900
10001100
1200
TotalCancers
2 - 4 5 - 6 7 8 - 10
Gleason Score
Nu
mb
er o
f C
ance
rs
Finasteride = 4368
Placebo - 4692
It now appears that increased sensitivity of detection may have
led to increase in HG tumors
Finasteride:
- 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
SpecificitySensitivity
PlaceboSensitivityFinasteride
Cancer vs. No Cancer
4.1 1.6 92.7% 24% 37.8%
Gleason >7 versus other
4.1 1.6 90.5% 39.2% 53%
Journal of the National Cancer Institute, 2006;98
Sensitivity
Finasteride Placebo p-value
Outcome
Prostate CA 21.3% 16.7% 0.013
Gleason > 7 26.1% 21.7% 0.25
Gleason > 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 f
ou
nd
at
bio
psy
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 grade
Low 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%.