Surrogate End point for Prostate Cancer- Specific Mortality After RP or EBRT A D’Amico J Nat Ca...
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![Page 1: Surrogate End point for Prostate Cancer- Specific Mortality After RP or EBRT A D’Amico J Nat Ca Inst 95,18 1376-1383. 2003.](https://reader036.fdocuments.us/reader036/viewer/2022070400/56649e625503460f94b5d6f2/html5/thumbnails/1.jpg)
Surrogate End point for Prostate Cancer- Specific
Mortality After RP or EBRT
A D’Amico
J Nat Ca Inst 95,18 1376-1383. 2003
![Page 2: Surrogate End point for Prostate Cancer- Specific Mortality After RP or EBRT A D’Amico J Nat Ca Inst 95,18 1376-1383. 2003.](https://reader036.fdocuments.us/reader036/viewer/2022070400/56649e625503460f94b5d6f2/html5/thumbnails/2.jpg)
Background
PSA recurrence post local treatment can lead to secondary therapy
Is PSA recurrence is surrogate end point for CAP specific mortality
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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
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Patients & Methods
8669 Patients from 2 data bases
5918 RP
2751 EBRT
Between Jan 1 1988- Jan 1 2002
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Patients & Methods
3 months neoadjuvant ADT in RP
Median age:
64.5 years RP
71.1 years RT
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Staging
DRE
PSA
TRUS prostate biopsy
Gleason score
Pre 1996- CT & bone scan
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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
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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
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Results
611(5918) post RP patients had PSA-defined recurrence
840(2751) post RT patients had PSA defined recurrence
12% & 20% respectively had PSA DT < 3 months
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Results
Statistically significant variables include:
Age at time of PSA defined recurrence PSA-DT < 3 months
Treatment modality not significant
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Conclusion
Post treatment PSA-DT < 3 months is a surrogate end point for CAP specific
mortality
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Preoperative PSA Velocity and the Risk of Death from
Prostate Cancer after Radical Prostatectomy
W. Catalona et al
NEJM July 8 2004
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Background
To evaluate whether prostate cancer specific mortality can be predicted from
variables present at diagnosis
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Methods
Clinical information collected prospectively- 1804 underwent RP
January 1 1989- June 1 2002
T1C & T2
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Methods
Exclusions:
689 single preoperative PSA
20 adjuvant radiotherapy
1095 study cohort
No adjuvant hormonal treatment
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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
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Follow up
Median FU 5.1 yearsNo patient lost to FU
Disease recurrence defined as 2 consecutive detectable PSA
366 recurrences & 84 deaths; 27 from CAP
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Statistical Analysis
PSA closest in time before diagnosis & all other values within 1 year
PSA velocity in year before diagnosis
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Results
PSA Velocity > 2ng/mL
Reduced time to recurrence
Death from CAP
Death from any cause
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Results: PSA V > 2ng/mL
Associated with increased LN mets
Advanced pathological stage
High grade disease
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Discussion
PSA Velocity > 2ng/mL
Enrolement in clinical trial
28% died of CAP in 7 years
Watchful waiting not good option
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Radical Prostatectomy versus Watchful Waiting in
Early Prostate Cancer
J. Johansson
NEJM May 2005
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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
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Methods
Prospective randomised trial comparing RP versus watchful waiting
1989 – 1999
695 men from 14 centres
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Methods
Age < 75 years
Clinical T2 or less
Life expectancy >10years
Well - moderately differentiated CAP
Bone scan –ve
PSA < 50ng/mL
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Methods
RP group all underwent LN dissection
Proceeded only if negative
WW group TURP
Hormonal treatment if evidence of local progression or dissemination
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Follow up
PSA
Bone scan CXR
Cause of death - patient files
Local Progression
WW: palpable or LUTS necessitating treatment
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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
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ResultsDeath from CAP
RP: 30WW: 50
Death from other causes50 vs 56
Among Non CAP death8 vs 1 – mets
13 vs 6 Local progressionDeath from any cause
106 vs 83
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Discussion
10 year disease-specific & overall mortality stat significant
Incidence of mets lower in RP group
Reduction in disease-specific greatest <65 years
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Conclusion
• Relative CAP death reduction by 44%
• 26% overall mortality
• 40% distant metastasis
• 67% local progression