Transcript Surrogate End point for Prostate Cancer

Surrogate End point for
Prostate Cancer- Specific
Mortality After RP or EBRT
A D’Amico
J Nat Ca Inst 95,18 1376-1383.
2003
Background
PSA recurrence post local treatment can
lead to secondary therapy
Is PSA recurrence is surrogate end point
for CAP specific mortality
Background
Short post treatment PSA-DT correlates
with time to distant recurrence after
PSA failure
Short PSA-DT is surrogate end point for
CAP death
Patients & Methods
8669 Patients from 2 data bases
5918 RP
2751 EBRT
Between Jan 1 1988- Jan 1 2002
Patients & Methods
3 months neoadjuvant ADT in RP
Median age:
64.5 years RP
71.1 years RT
Staging
DRE
PSA
TRUS prostate biopsy
Gleason score
Pre 1996- CT & bone scan
Follow-up
Entire Cohort
Median FU RP: 7.1 yrs
Median FU RT: 6.9 yrs
PSA –defined recurrence
RP 4.1 yrs
RT 3.8 yrs
154 deaths, 110 from CAP
PSA-DT
Minimum of 3 measurements
Minimum separation 3 months
PSA increase > 0.2ng/mL
• Post RP <0.2 (0), 0.3, 0.6
• Post RT 0.6, 0.9, 1.2, 1.8
Results
611(5918) post RP patients had PSAdefined recurrence
840(2751) post RT patients had PSA
defined recurrence
12% & 20% respectively had PSA DT <
3 months
Results
Statistically significant variables include:
Age at time of PSA defined recurrence
PSA-DT < 3 months
Treatment modality not significant
Conclusion
Post treatment PSA-DT < 3 months is a
surrogate end point for CAP specific
mortality
Preoperative PSA Velocity
and the Risk of Death from
Prostate Cancer after
Radical Prostatectomy
W. Catalona et al
NEJM July 8 2004
Background
To evaluate whether prostate cancer
specific mortality can be predicted from
variables present at diagnosis
Methods
Clinical information collected
prospectively- 1804 underwent RP
January 1 1989- June 1 2002
T1C & T2
Methods
Exclusions:
689 single preoperative PSA
20 adjuvant radiotherapy
1095 study cohort
No adjuvant hormonal treatment
Methods
Median age 65.4 yrs (43-83)
71% T1c
95% PSA < 10ng/mL
Median PSA4.3ng/mL
PSA Velocity > 2ng/mL
143,65 and 54 men diagnosis after 1,2 or 3
biopsies
Follow up
Median FU 5.1 years
No patient lost to FU
Disease recurrence defined as 2
consecutive detectable PSA
366 recurrences & 84 deaths; 27 from
CAP
Statistical Analysis
PSA closest in time before diagnosis & all
other values within 1 year
PSA velocity in year before diagnosis
Results
PSA Velocity > 2ng/mL
Reduced time to recurrence
Death from CAP
Death from any cause
Results: PSA V > 2ng/mL
Associated with increased LN mets
Advanced pathological stage
High grade disease
Discussion
PSA Velocity > 2ng/mL
Enrolement in clinical trial
28% died of CAP in 7 years
Watchful waiting not good option
Radical Prostatectomy
versus Watchful Waiting in
Early Prostate Cancer
J. Johansson
NEJM May 2005
Background
Initial results in 2002
Followup data- 10 year results
Risk of death due to CAP reduced by 50%
Distant metastasis 37%
No stat sig reduction in mortality
Methods
Prospective randomised trial comparing
RP versus watchful waiting
1989 – 1999
695 men from 14 centres
Methods
Age < 75 years
Clinical T2 or less
Life expectancy >10years
Well - moderately differentiated CAP
Bone scan –ve
PSA < 50ng/mL
Methods
RP group all underwent LN dissection
Proceeded only if negative
WW group TURP
Hormonal treatment if evidence of local
progression or dissemination
Follow up
PSA
Bone scan CXR
Cause of death - patient files
Local Progression
WW: palpable or LUTS necessitating
treatment
Results
347 RP & 348 WW
76% T2
12% T1c
By 2003 21 in RP had no surgery
43 in WW curative surgery
LN mets 23
Results
Death from CAP
RP: 30
WW: 50
Death from other causes
50 vs 56
Among Non CAP death
8 vs 1 – mets
13 vs 6 Local progression
Death from any cause
106 vs 83
Discussion
10 year disease-specific & overall
mortality stat significant
Incidence of mets lower in RP group
Reduction in disease-specific greatest
<65 years
Conclusion
• Relative CAP death reduction by 44%
• 26% overall mortality
• 40% distant metastasis
• 67% local progression