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 PSA-defined 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 yearsNo 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

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

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