1. Rising PSA after Radical Prostatectomy. My Approach. Dr Manish Patel Urological Cancer Surgeon Urological Cancer Surgeon Westmead Hospital University of Sydney

2. Definition of BCR No data evaluating super sensitive PSA assay (ie. Threshold <0.1ng/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 >0.4ng/ml, 79% demonstrate CP. PSA Working Group Definition: >0.4ng/ml with one subsequent rise. This definition is the best predictor for later CP.

3. Low PSA after RRP PSA <0.29ng/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 % BCRYrs to BCR % CPYrs to CP % PCSMYrs to PCSM Pound19971X >0.215 (15yr)3.534 (15yr)818 (15yr)13 D’Amico10952X >0.233 (5yr) Roehl34782X >0.218 (10yr)3.236 (10yr) Jhaveri11321X >0.219 (10yr)1.926 (10yr) Hull10002X >0.415 (10yr)23 (10yr) Bianco17461X >0.223 (10yr)2.8 (10yr) Only 20-30% with BCR suffer CP Only 20-30% with BCR suffer CP <1/2 of these men with CP die of PC <1/2 of these men with CP die of PC

5. 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

6. 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 <3m 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.

9. Algorithms Cancer Specific Survival BCR After RRP. Freedland et.al.

10. 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 (positive=158ng/ml), (negative= 11.3ng/ml) Prostascint –No difference in RT response to + and - scans PET –High false positive and image resolution problems

11. Localised or Systemic? Nomogram Stephenson et.al

12. 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.

13. 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.

14. 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 GS>8 or PSADT <12m only. –No difference in survival TrialNo.Defn TxStageEarlyLateBenefit ECOG (Messing)98RPN1, MO85% (OS)63% (OS)Yes MRC934NoneM030% (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

15. Do Not Use HT when Not Needed Hyperlipidaemia Insulin Resistence Decreased libido Cognitive impairment Osteoporosis Acute Cardiovascular Events

16. My Approach Rising PSA after RP. PSA>0.4ng/ml X2 Negative CT/BS Life Expectancy >5-10yrs High risk of CP/PCSM YESNO High likelihood of Durable Response form salvage XRT Using Nomogram YES NO Observation with Serial PSA and imaging Progression Hormone Therapy Salvage RT