Tracy M' Downs, M'D'

1
RISING PSA AFTER LOCAL DEFINITIVE THERAPY
Patient Outcomes and Management Strategies
C.U.R.E.

• Tracy M. Downs, M.D.
• Division of Urology
• Program in Urologic Oncology
• University of California, San Diego
• VA San Diego Healthcare System

2
RISING PSA AFTER LOCAL DEFINITIVE THERAPY
Trying to make sense out of a very complicated
part of urologic patient care
3
PROSTATE CANCERPatient selection - Risk
Assessment
4
Prostate CancerPre-Treatment Risk Assessment
Predicting Recurrence Before Local Definitive
Therapy

5
Prostate Cancer Risk Factors For PSA
Recurrence

• Pretreatment Factors
• Higher Stage
• Biopsy Gleason Score (any pattern 4 or sum gt7)
• Preoperative PSA ( gt 10ng/ml)
• Greater number of positive biopsies
• Pathologic Factors
• Higher stage (SVI, LN involvement)
• Higher Gleason grade
• Positive Surgical margins
• DNA Ploidy
• Vascular Invasion

6
High Risk Prostate CancerNatural History

• 20 to 35 of newly diagnosed patients are
  classified as High Risk (HR)
• Grossfeld et al. Urology 59 560, 2002
• Most series disappointing outcomes
• 50 to 100 biochemical disease progression within
  5 yrs. of local treatment
• In the Post-PSA era
• Contemporary High Risk patients may remain good
  candidates for localized therapy alone if the
  cancers are detected early

7
High Risk Prostate CancerGoals of Risk Assessment

• Identify Two groups of High Risk Patients
• (1) HR Patients who can be treated with
  localized therapy alone
• (2) HR Patients in whom localized therapy is
  destined to fail
• Early Systemic Therapy
• Combination Treatment
• Novel Clinical Trials

8
High Risk Prostate CancerPredicting Recurrence
After Radical Prostatectomy

9
High Risk Prostate CancerRationale

• UCSF
• 547 consecutive patients with HR Prostate Ca
• 120 Patients UCSF
• 427 Patients - CaPSURE Database
• Definition for HR Prostate Cancer
• PSA at Diagnosis gt 20ng/ml
• Clinical Stage T2c or T3 disease (1992 AJCC TNM)
• Gleason Summary Score 8 to 10
• Radical Prostatectomy June 1988 Sept. 2000

Grossfeld et al. J Urol. 169, 2003
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High Risk Prostate CancerRationale

• UCSF
• Exclusion Criteria
• Neoadjuvant Androgen Deprivation Therapy
• Radiation therapy prior to Radical Prostatectomy
• Adjuvant Therapy (Radiation or Androgen
  Deprivation) within 6 months of Surgery
• Primary Endpoint
• Disease Recurrence after Radical Prostatectomy
• Definition
• Detectable PSA after Surgery (PSA gt 0.2ng/ml on 2
  consecutive measurements)
• Second Prostate Cancer Treatment gt 6 months
  following Surgery
• Median Follow-up 3.1 years

Grossfeld et al. J Urol. 169, 2003
11
High Risk Prostate CancerResults - Overall

• Median Follow-up 3.1 years
• Overall Disease recurrence 32
• Average PSA at Diagnosis 14.8ng/ml
• 25 of patients Gleason 8 to 10
• 95 abnormal DRE nodule(s)
• 40 had gt 66 core () biopsies
• 18 had gt 1 High Risk Dz. Characteristic

Grossfeld et al. J Urol. 169, 2003
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High Risk Prostate Cancer()Dz. Recurrence vs
(-) No Dz. Recurrence
Grossfeld et al. J Urol. 169, 2003
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High Risk Prostate CancerAge and Ethnicity
Grossfeld et al. J Urol. 169, 2003
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High Risk Prostate CancerPSA and Gleason Score
Grossfeld et al. J Urol. 169, 2003
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High Risk Prostate Cancer() Positive Biopsies
Grossfeld et al. J Urol. 169, 2003
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High Risk Prostate Cancer() Positive Biopsies
Grossfeld et al. J Urol. 169, 2003
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Prostate CancerPredicting Disease Progression
After Local Definitive Therapy Has Failed

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RISING PSAAFTER LOCAL DEFINITIVE THERAPYOUTLINE

• Rising PSA Clinical Importance
• Definition of Biochemical Failure
• Natural History of Disease Progression
• Diagnostic Approaches
• Role of Salvage Therapy
• Surgery or Radiotherapy
• Role of Systemic Hormones
• Appropriate timing for clinical trials

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RISING PSAAFTER LOCAL DEFINITIVE THERAPY

• Moul et al. estimates that 50,000 men/yr.
• May have PSA-only recurrence after
• definitive treatment
• Moul JW J Urol 2000 1631632-1642
• Biochemical Failure occurs in 35 of patients
• PSA relapse precedes clinical disease recurrence
  by 3-5 years

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Rising PSA Patients What is Known?
3263 pts 329 pts 144 pts (44)
78 (24)
RP
Death
PSA Recurrence (PSAgt 0.2)
Distant Mets
6.5 years
3 years
7 years
Metastasis-free Survival
Metastases to Death
PSA Relapse
Overall Survival
Metastasis-free survival is variable (6 to 84
at 7 years) Effect of androgen deprivation on
overall survival is unknown Eisenberger et
al. Proc Am Soc Clin Oncol 2003. Pound, et al.
Jama 1999.
21
Defining PSA Progression After Radical
Prostatectomy

• Retrospective analysis (n2,782) cT1-T2
• Different cut-points used to define recurrence
• 10 year PFS by cut-point
• 0.2 ng/ml 43
• 0.3 ng/ml 54
• 0.4 ng/ml 59
• 0.5 ng/ml 61

Adapted from Amling CL, et al. J Urol 2001.
22
Defining PSA Progression After Radical
Prostatectomy

• Retrospective Analysis (n358) using various PSA
  cutpoints

Adapted from Freedland S, et al. J Urol 165
1146, 2001
23
RADICAL PROSTATECTOMY Biochemical Relapse-Free
Survival
24
RADICAL PROSTATECTOMY UCSF - PSA - Free Relapse
- Risk Stratified
25
Defining PSA Progression After External Beam
Radiation Therapy

• Different PSA serum t½ (1.9 - 3 months)
• Nadir PSA over 17-32 months
• Consensus Panel Definition (ASTRO 1997)
• Three consecutive increases in PSA
• Not justification for additional treatment
• Not equivalent to clinical failure
• Appropriate end point for clinical trials
• For clinical trials
• Date of Failure midpoint between post-XRT PSA
  nadir and the first of 3 consecutive raises
• Back-dating may lead to biased estimates of
  Failure Rates

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Defining PSA Progression After External Beam
Radiation Therapy

• Multi-institutional Outcome Study (n 4839)
• Tested different Definitions of PSA failure
• 2 PSA rises of at least 0.5ng/ml each, backdated
• PSA gt current nadir PSA2ng/ml
• PSA gt current nadir PSA3ng/ml
• PSA nadir is a significant predictor of outcome
• PSA gt2 worse outcome

Adapted from Kuban D, et al. World J Urol. 2003
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Risk of Progression after PSA Failure

• Predictors of Disease Progression and Outcomes
• Time to Biochemical Relapse
• Greater or Shorter than 2 years
• PSA Doubling Time (PSADT)
• Prostatectomy Gleason sum
• GS 5-7 vs. GS 8-10

Eisenberger et al. Proc Am Soc Clin Oncol 2003.
Pound, et al. Jama 1999.
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Risk of Progression after PSA Failure

• Predictors of Disease Progression and Outcomes
• Time to Biochemical Relapse
• Greater or Shorter than 2 years
• PSA Doubling Time (PSADT)
• Prostatectomy Gleason sum
• GS 5-7 vs. GS 8-10

Eisenberger et al. Proc Am Soc Clin Oncol 2003.
Pound, et al. Jama 1999.
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Risk of Progression after PSA Failure

• Predictors of Disease Progression and Outcomes
• Time to Biochemical Relapse
• Greater or Shorter than 2 years
• PSA Doubling Time (PSADT)
• Prostatectomy Gleason sum
• GS 5-7 vs. GS 8-10

Eisenberger et al. Proc Am Soc Clin Oncol 2003.
Pound, et al. Jama 1999.
30
Definition of PSA Doubling Time (PSADT)
(PSA) vs. time
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Risk of Progression after PSA Failure

• Predictors of Disease Progression and Outcomes
• Time to Biochemical Relapse
• Greater or Shorter than 2 years
• PSA Doubling Time (PSADT)
• Prostatectomy Gleason sum
• GS 5-7 vs. GS 8-10

Eisenberger et al. Proc Am Soc Clin Oncol 2003.
Pound, et al. Jama 1999.
32
Natural History of Prostate Cancer Probability
of metastasis-free survival afterPSA Relapse
P lt0.0001
Pound Tables 1999
Adapted from Eisenberger, et al. ASCO 2003.
33
Natural History of Prostate Cancer Probability
of metastasis-free survival afterPSA Relapse
P lt0.0001
Pound Tables 1999
Adapted from Eisenberger, et al. ASCO 2003.
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Important Aspects of Updated Pound Tables
2003Pound Tables Revisited

• Confirmed PFS in Good-risk patients
• Long and different from High-Risk patients
• No data for prolonged PSADT in high GS/lt 2-y
  recurrence
• Identify candidates for treatment
• Time to bone metastasis
• Appropriate timing for clinical trials
• PSADT may be a potential surrogate for overall
  survival

PFS Progression Free Survival
35
Independent Predictors of Outcome after PSA
relapse following local definitive therapy

• Time to Biochemical Relapse
• PSA Doubling Time (PSADT)
• Prostatectomy Gleason sum

36
Prostate CancerIdentifying PSA Recurrence And
Its Site Local vs Distant Recurrence

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Identifying PSA Recurrence Local vs
Distant Recurrence

• PSA nadir is typically reached by 6 wks. After
  Radical Prostatectomy
• Low-risk patients typically have local dz.
  recurrence
• SVI and LN patients typically have distant dz.
  Recurrence

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Identifying PSA Recurrence Local vs
Distant Recurrence

• PSA Velocity and dz. Recurrence
• PSAV lt 0.75ng/ml/yr. 94 Local Recurrence
• PSAV gt0.75ng/ml/yr. 50 Distant Recurrence
• PSADT lt 6 mos. Distant Disease
• PSA only failure patients
• Outcomes are similar (UCSF Experience)
• PSA Only relapse/no anastamotic biopsy done
• PSA relapse/ () anastamotic biopsy done

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Identifying PSA Recurrence Local vs
Distant Recurrence

• Role of TRUS Guided Biopsy
• 99 patients with PSA failure after RP
• 41/99 patients (41)
• Local recurrence on TRUSBx
• Most common site(s)
• Bladder neck and Anastamosis (34/41 -82 )
• Overall sensitivity of TRUS - 76
• Overall specificity of TRUS 67

Leventis et al. Radiology 2001 219432-439
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Identifying PSA Recurrence Local vs
Distant Recurrence

• Role of TRUS Guided Biopsy
• in PSA Relapse
• Not indicated after RP
• Indicated after
• Radiotherapy
• Cryosurgery ?

Take Home Points!
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Identifying PSA Recurrence Local vs
Distant Recurrence

• Role of CT and Bone Scan
• No role for CT scan
• Only used in the past to detect local dz.
  recurrence
• Bone scan () following surgery
• 3.5 1st year following treatment
• 10.4 0 to 36 months following treatment
• (3 years)

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Identifying PSA Recurrence Local vs Distant
Recurrence
The Role of CT Scan
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Identifying PSA Recurrence Local vs Distant
Recurrence
The Role of Bone Scan
44
Local vs. Distant Recurrence Algorithm
Systemic Therapy
Androgen Deprivation CAB - IAB - HD Casodex
Clinical Trial
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Local vs. Distant Recurrence Algorithm
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Systemic Therapy for PSA Recurrence What
are the options?

• Androgen Deprivation
• Continuous
• Combined ADT vs Castration Alone (Surgical or
  Pharmacologic)
• Intermittent Therapy with CAB?
• Single Agent Anti-Androgens
• Novel Therapeutics
• Target Therapy
• Adjuvant Chemotherapy

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Natural History of Prostate Cancer Timing for
Androgen Deprivation

• Adjuvant AD with XRT vs. AD at progression
• Bolla (EORTC 22863) - Crossover at clinical
  progression
• (PD Metastasis in 72/90 (80)
• Pilepich (RTOG 8531) - Crossover at clinical
  progression
• (Was not defined)
• Adjuvant AD after RP in Patients N () vs. AD at
  Progression
• Messing (ECOG 3886) - Crossover at clinical PD
• - PD Metastasis in 33/37 (89)

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Natural History of Prostate Cancer Timing for
Androgen Deprivation

• Other Retrospective Studies
• AD prior to clinical metastasis vs. AD after
  clinical metastasis
• No survival advantages, contradicting other
  studies
• Dotan, et al. ASCO 2003.

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Natural History of Prostate Cancer Timing for
Androgen Deprivation

• MRC - AD at Diagnosis of Metastases vs. AD at
  symptomatic progression (or not at all)

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RTOG 8531 Phase III Radiotherapy followed by
Adjuvant Zoladex
Lifelong AD
Survival
n 977 Non-metastatic Prostate Cancer cT1-T3, N
Clinical Progression
Cross-over AD
No AD
Survival
Adapted from Pilepich, et al, ASCO 2003.
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RTOG 8531 Details

• Patient Selection
• T1-T2 Patients Node evaluation by CT or Surgery
• T3 Patients No node evaluation required ?
• T any Patients 28 were N()
• RP with () SV and/or Positive Surgical Margins
  15
• Central GS 2-6 30 - GS 7 38 - GS 8-10 32
• Radiotherapy Field and Dose
• Pelvic Radiotherapy for Node () Patients
• No need for Prostate Radiotherapy for RP patients
• Prostate Dose 65Gy (60 Gy if POP)
• Minimum Pelvis dose was 44Gy

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RTOG 8531 10-year outcome estimates ASCO 2003
Update
Adapted from Pilepich, et al, ACO 2003.
53
RTOG 8531 Issues from Update

• Heterogeneous Group ( Post- RP)
• Pelvic Radiotherapy was given to N () only
• GS 2-6 (30) No survival benefit (p ns)
• GS 7 (38) Survival Advantage (p0.042)
• GS 8-10 (32) Survival Advantage (p0.0061)
• Definition of Deferred AD
• At PSA progression or PD from Bone Mets ?
• Confirmed Bollas study Long-term AD survival
  advantage in high-risk patients
• AD was given as adjuvant and not concurrent
• Conflict with new RTOG 9413 data

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Adjuvant AD following RP in Node Positive
Patients Messing Study
Lifelong AD (Goserelin or Orchiectomy) N 47
Survival
n 98 Post- RP Node ()
Observation N 51
Distant Mets n 33
Cross-over AD
Survival
Adapted from Messing et al. Proc AUA, 2003
55
Adjuvant AD in RP Node () Patients Issues

• Median Age 65.9 years
• Small Sample size with diverse group of pts
• 20 had Biochemical failure after RP
• Detectable PSA
• Median Follow-up 10 years
• Median Survival only reached in the observation
  arm

Messing, et al. Proc AUA 2003.
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Early Androgen Deprivation Conclusions

• Prolongs life when used adjuvantly in T3 or N ()
  patients
• treated with XRT (Pilepich)
• Might do even better with Neo/concurrent AD
  (Roach)
• Prolongs life in N () patients treated with RP
  (Messing)
• Unclear if it prolongs life in patients with PSA
  relapse
• Further prospective data required

57
Early Androgen Deprivation Conclusions

• Prolongs life when used adjuvantly in T3 or N ()
  patients
• treated with XRT (Pilepich)
• Might do even better with Neo/concurrent AD
  (Roach)
• Prolongs life in N () patients treated with RP
  (Messing)
• Unclear if it prolongs life in patients with PSA
  relapse
• Further prospective data required

58
Early Androgen Deprivation Conclusions

• Prolongs life when used adjuvantly in T3 or N ()
  patients
• treated with XRT (Pilepich)
• Might do even better with Neo/concurrent AD
  (Roach)
• Prolongs life in N () patients treated with RP
  (Messing)
• Unclear if it prolongs life in patients with PSA
  relapse
• Further prospective data required

59
Early Androgen Deprivation Conclusions

• Prolongs life when used adjuvantly in T3 or N ()
  patients
• treated with XRT (Pilepich)
• Might do even better with Neo/concurrent AD
  (Roach)
• Prolongs life in N () patients treated with RP
  (Messing)
• Unclear if it prolongs life in patients with PSA
  relapse
• Further prospective data required

60
Total Androgen Blockade vs Monotherapy

• Is there an advantage ????
• Total Androgen Blockade LhRH AA
• Monotherapy LhRH only

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Total Androgen Blockade vs Monotherapy

• NO

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Total Androgen Blockade vs Monotherapy

• Studies dating back to 1983
• 27 prospectively randomized trials
• Different regimens of TAB
• 8,000 patients
• NO compelling evidence of a clinically meaningful
  advantage for TAB

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Continuous Androgen Deprivation Side Effects

• Are there better therapies ?
• Acute Side Effects
• Hot Flashes, Night Sweats
• Gynecomastia and Breast Tenderness
• Loss of Libido, Loss of Potency
• Weight Gain
• Long Term Side Effects
• Anemia
• Muscle Weakness
• Cognitive Impairment
• Bone Density Loss

64
Intermittent Androgen Deprivation Therapy (ADT)

• Goals
• Decrease acute and chronic side-effects
• Prolong time to development of androgen-independen
  ce
• Improve quality of life and minimizes cost
• Rationale
• Progression to androgen independence may be
  driven, in part, by androgen deprivation
• Androgen deprivation leads to activation of
  cellular and molecular pathways that mediate
  tumor progression
• Intermittent androgen replacement may delay
  progression to androgen independence in
  pre-clinical models

65
Intermittent Androgen DeprivationUCSF Treatment
Algorithm
66
Intermittent Androgen DeprivationUCSF Treatment
Algorithm
67
Intermittent Androgen Deprivation UCSF
Experience

• Retrospective Analysis (n61)
• 34 untreated
• 8 RP
• 10 RT
• 6 RP/RT
• 3 Cryosurgery
• No evidence of Metastasis
• Initial median PSA 16.0 ng/ml
• Mean Follow-up 30 months

Adapted from Grossfeld G, et al Urology 2001.
68
Intermittent Androgen Deprivation UCSF
Experience
Cycling Characteristics of Patients on IAB
Adapted from Grossfeld G, et al Urology 2001.
69
Intermittent Androgen Deprivation Failure
UCSF Experience

• - Median follow-up
• 30 months (7-60)
• - Five pts failed IAB
• 24-33-48-57-58 months post starting IAB
• 2 pts failed at C2
• 2 pts failed at C4
• 1 pt failed at C5

Adapted from Grossfeld G, et al Urology 2001.
70
Intermittent Androgen Deprivation Quality of
Life (Qol)

• -Serum testosterone usually returns to normal
  levels
• within 3-6 months
• -Energy level and sense of well-being improve in
  
• more than 50 of patients
• -Hot flashes resolve in 60
• -Libido and erectile function improve in many
  patients
• -Less impact in Cognitive function
• -Less likelihood of developing Anemia low
  Testosterone
• -Less impact in Bone Mineral Density c/w
  Continuous AD

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Intermittent Androgen Deprivation Health
Related Qol (HRQol)
Higher Scores Better QOL
Adapted from Grossfeld G, et al Urology 2001.
72
Intermittent Androgen Blockade Conclusions

• -Same efficacy as continuous AD
• -May delay the onset of AiPC
• -Clearly, less side effects c/w CAB
• -QOL improves
• -Appears to have less effects in BMD

73
Anti-Androgen (AA) Monotherapy Rationale

• -Inhibit binding of Testosterone and DHT to
  androgen
• receptor both centrally and peripherally
• -Should be as effective as castration
• Potency/Libido sparing
• Improved QOL
• Easy administration
• ? Decreased cost
• -Physical Activity and Sexual functioning favor
  AA
• p 0.046 and p 0.029

74
Bicalutamide Monotherapy Current Status
Updated Trials
75
Bicalutamide Monotherapy Current Status -
High Dose AA Trials
Updated Trials
76
Bicalutamide Monotherapy vs Castration
Side Effect Profiles
Adapted from Iversen P, et al. J Urol 2000
77
Bicalutamide Monotherapy vs Castration
Side Effect Profiles
Adapted from Iversen P, et al. J Urol 2000
78
High Dose Bicalutamide Conclusions

• -Same efficacy as continuous AD
• -May delay the onset of AiPC
• -Clearly, less side effects c/w CAB
• -QOL improves
• -Appears to have less effects in Bone Mineral
  Density (BMD)

79
Non-Hormonal Systemic TherapyNovel
Therapeutics

• Difficult to assess efficacy
• Traditional objective response criteria
• Time to progression
• Symptomatic improvement
• PSA evaluation
• PSA decline
• PSA slope
• Survival

80
Non-Hormonal Systemic TherapyNovel
Therapeutics

• -Cell cycle regulation
• -Angiogenesis
• -Signal transduction
• -Immunotherapeutics
• -Pro-apoptotic agents
• -Viral/Gene therapy
• -Differentiating agents

81
Immunotherapy for PSA relapse APC8015 Provenge
in Combination with Bevacizumab

• APC8015 (Provenge) is a cellular product
  consisting of dendritic cells (DC) pulsed with a
  PAP (Prostatic Acid Phosphatase)-GM-CSF construct
  (PA2024).
• Provenge administration has previously been shown
  to enhance T cell reactivity against PAP, an
  antigen expressed in 95 of prostate cancers.
• Phase I and phase II studies has demonstrated
  safety and PSA declines gt 50 in 3 of 19 patients
  with AiPCA.
• Pts demonstrating immune response to PAP had a
  longer time to disease progression.

82
Granulocyte-macrophage colony-stimulating factor
(GM-CSF)

• -GM-CSF promotes the proliferation,
  maturation and migration of DC.
• -Increased co-stimulatory molecule
  expression on host bone marrow-derived DC as a
  result of GM-CSF exposure leads to cross-priming
  of -T cells, stimulating T cell responses.

tumor cells
Anti-cancer immune response
CD8 T cell
GM-CSF
APC
CD4 T cell
83
Prostate CancerPSA Relapse Summary

• -Crucial to Identify Patients who will benefit
  from Local
• and or systemic therapy
• -Early intervention is important
• How early is early remains a question
• -Patients with Local Regional disease will
  benefit from XRT
• If plan to give XRT ( Whole Pelvis NCAHT) vs.
  longer period ?
• 50 of patients undergoing Salvage XRT will
  become NED
• -IAB has same efficacy of CAB High Dose Casodex
  similar efficacy
• Need further prospective studies
• -Slow PSADT, No clinical evidence of disease,
  desire of delaying AD
• Great candidates for Clinical Trials

84
Prostate CancerPSA Relapse Summary

• -Crucial to Identify Patients who will benefit
  from Local
• and or systemic therapy
• -Early intervention is important
• How early is early remains a question
• -Patients with Local Regional disease will
  benefit from XRT
• If plan to give XRT ( Whole Pelvis NCAHT) vs.
  longer period ?
• 50 of patients undergoing Salvage XRT will
  become NED
• -IAB has same efficacy of CAB High Dose Casodex
  similar efficacy
• Need further prospective studies
• -Slow PSADT, No clinical evidence of disease,
  desire of delaying AD
• Great candidates for Clinical Trials

85
Prostate CancerPSA Relapse Summary

• -Crucial to Identify Patients who will benefit
  from Local
• and or systemic therapy
• -Early intervention is important
• How early is early remains a question
• -Patients with Local Regional disease will
  benefit from XRT
• If plan to give XRT ( Whole Pelvis NCAHT) vs.
  longer period ?
• 50 of patients undergoing Salvage XRT will
  become NED
• -IAB has same efficacy of CAB High Dose Casodex
  similar efficacy
• Need further prospective studies
• -Slow PSADT, No clinical evidence of disease,
  desire of delaying AD
• Great candidates for Clinical Trials

86
Prostate CancerPSA Relapse Summary

• -Crucial to Identify Patients who will benefit
  from Local
• and or systemic therapy
• -Early intervention is important
• How early is early remains a question
• -Patients with Local Regional disease will
  benefit from XRT
• If plan to give XRT ( Whole Pelvis NCAHT) vs.
  longer period ?
• 50 of patients undergoing Salvage XRT will
  become NED
• -IAB has same efficacy of CAB High Dose Casodex
  similar efficacy
• Need further prospective studies
• -Slow PSADT, No clinical evidence of disease,
  desire of delaying AD
• Great candidates for Clinical Trials

87
Prostate CancerPSA Relapse Summary

• -Crucial to Identify Patients who will benefit
  from Local
• and or systemic therapy
• -Early intervention is important
• How early is early remains a question
• -Patients with Local Regional disease will
  benefit from XRT
• If plan to give XRT ( Whole Pelvis NCAHT) vs.
  longer period ?
• 50 of patients undergoing Salvage XRT will
  become NED
• -IAB has same efficacy of CAB High Dose Casodex
  similar efficacy
• Need further prospective studies
• -Slow PSADT, No clinical evidence of disease,
  desire of delaying AD
• Great candidates for Clinical Trials

88
Prostate CancerPSA Relapse Summary

• -Crucial to Identify Patients who will benefit
  from Local
• and or systemic therapy
• -Early intervention is important
• How early is early remains a question
• -Patients with Local Regional disease will
  benefit from XRT
• If plan to give XRT ( Whole Pelvis NCAHT) vs.
  longer period ?
• 50 of patients undergoing Salvage XRT will
  become NED
• -IAB has same efficacy of CAB High Dose Casodex
  similar efficacy
• Need further prospective studies
• -Slow PSADT, No clinical evidence of disease,
  desire of delaying AD
• Great candidates for Clinical Trials

89
THE END

• Thank You