Rising PSA after Radical Prostatectomy. My Approach.

1
Rising PSA after Radical Prostatectomy.My
Approach.

• Dr Manish Patel
• Urological Cancer Surgeon
• Westmead Hospital
• University of Sydney

2
Definition of BCR

• No data evaluating super sensitive PSA assay (ie.
  Threshold lt0.1ng/ml)
• PSA t ½ is 3.1 days. Measure PSA at least 4
  weeks after surgery
• No consensus on BCR definition. (0.2ng/ml to
  0.6ng/ml)
• EAU 0.2ng/ml with 2 subsequent rises.
• Amling et.al. PSA 0.2-0.29ng/ml, 50 stable in
  this range.
• CP rate increased as threshold increased.
• PSA gt0.4ng/ml, 79 demonstrate CP.
• PSA Working Group Definition
• gt0.4ng/ml with one subsequent rise.
• This definition is the best predictor for later
  CP.

3
Low PSA after RRP

• PSA lt0.29ng/ml has a low incidence of CP
• Possible
• Recurrence of low-volume or indolent CaP.
• Benign PSA production.
• 61 of men with Benign positive margins will
  have detectable PSA(Djavan et.al.)

4
Natural History of BCR
No. BCR Defn BCR Yrs to BCR CP Yrs to CP PCSM Yrs to PCSM
Pound 1997 1X gt0.2 15 (15yr) 3.5 34 (15yr) 8 18 (15yr) 13
DAmico 1095 2X gt0.2 33 (5yr)
Roehl 3478 2X gt0.2 18 (10yr) 3.2 36 (10yr)
Jhaveri 1132 1X gt0.2 19 (10yr) 1.9 26 (10yr)
Hull 1000 2X gt0.4 15 (10yr) 23 (10yr)
Bianco 1746 1X gt0.2 23 (10yr) 2.8 (10yr)

• Only 20-30 with BCR suffer CP
• lt1/2 of these men with CP die of PC

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Natural History of BCR

• 1997 RRP at John Hopkins Hospital
• 304 had BCR
• Development of CP depended on GS, time to
  recurrence and PSADT
• Equal risk of PCSM and other causes mortality.
• For Every 100 men treated with RRP
• 15-30 will develop BCR
• 2-6 will die from CaP

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BCR and Risk Prediction

• Need to know
• 1. Severity of the disease.
• 2. Location of the disease.

Severity- Predicted by GS and Time to Recurrence
Gleason Score
Time to Recurrence
Freedland et.al
7
PSA DT- Strong Predictor of PC Death

• PSADT lt3m associated with high death rate.
• There is however a chance of mortality at all
  doubling times.

Freedland et.al
8
Algorithms

• Nomograms assist in evaluating multiple
  variables.
• Assess risk for developing CP and PCSM
• Cancer Specific
  Survival BCR After RRP.

Pound et.al.
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Algorithms Cancer Specific Survival BCR After
RRP.
Freedland et.al.
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Localised or Systemic?

• Options for Investigation
• Prostate Fossa Biopsy
• Poor sensitivity.
• MRI
• High sensitivty for pelvic mass but not
  correlated with pathology.
• Endorectal probe 95 sensitivity but at median
  PSA 2.18ng/ml
• CT scan
• Bone Scan
• Median PSA (positive158ng/ml), (negative
  11.3ng/ml)
• Prostascint
• No difference in RT response to and - scans
• PET
• High false positive and image resolution problems

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Localised or Systemic?Nomogram
Stephenson et.al
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Estimating Life Expectancy

• Important as patient may not be at risk of CP or
  PCSM
• Many ways of calculating, which incorporate age
  and co-morbidity.
• Nomogram by Cowen et.al.- 70 accuracy.

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Salvage Radiotherapy

• Response depends on likihood of local disease.
• Stephensen et.al. Nomogram (also flowchart)
• Katz et.al.
• Also found absence of SM, absence of ECE and
  SVI as poor pronostic factors.
• Pazona- 5 yr PFS was 40.
• Salvage RT dose range from 60Gy to 70Gy.
• 50 loss of potency
• No change in continence
• Higher BNC rate.

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Hormonal Therapy

• HT with CP (metastases) is well established.
• HT earlier is controversial (PSA only).
• No randomised trials (TOAD is on going in
  Australia)
• Moul et.al. Early(MO) vs Late HT (M1) for BCR
  after RRP
• CP was delayed in men with GSgt8 or PSADT lt12m
  only.
• No difference in survival

Trial No. Defn Tx Stage Early Late Benefit
ECOG (Messing) 98 RP N1, MO 85 (OS) 63 (OS) Yes
MRC 934 None M0 30 (OS) 23 (OS) Yes
4 Other clinical trials show no benefit of early
HT in MO disease EPC Trial showed higher risk of
death with Casodex in Clinically Localised CaP
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Do Not Use HT when Not Needed

• Hyperlipidaemia
• Insulin Resistence
• Decreased libido
• Cognitive impairment
• Osteoporosis

Acute Cardiovascular Events
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My Approach
Rising PSA after RP. PSAgt0.4ng/ml X2 Negative
CT/BS
Life Expectancy gt5-10yrs High risk of CP/PCSM
YES
NO
Observation with Serial PSA and imaging
High likelihood of Durable Response form salvage
XRT Using Nomogram
Progression
YES
NO
Hormone Therapy
Salvage RT