1. Is Radical Prostatectomy Adequate For High Risk Prostate Cancer?
Dr Manish Patel
Urological Cancer Surgeon
Westmead Hospital
University of Sydney

2. What is High Risk
High Risk For Recurrence and Progression following Definitive Therapy. Localised High Risk Gleason score 8-10 PSA >20ng/ml Locally Advanced Clinical T3 Lymph node positive Excluded: Clinical T4 N2 or distant metastatic disease

3. Guidelines EAU AUA NCCN
Option: Although active surveillance, interstitial prostate brachytherapy, external
beam radiotherapy, and radical prostatectomy are options for the management of
patients with high-risk localized prostate cancer, recurrence rates are high.
NCCN
For: cT3a or Gleason 8-10 or PSA>20ng/ml
Radical prostatectomy (selected patients with no fixation, low volume, + plevic lymph node dissection.)
ADT + XRT (3 years)

4. High Risk- Localised Prostate Cancer Down Grading is Common
Donohue et.al. –MSKCC 238 Men had biopsy Gleason score % had Gleason score <7 in prostate specimen.
Manoharan et.al- 31% down grading
Grossfeld et.al. -38% down grading

5. High Risk- Localised Prostate Cancer
Very significant BFS in men down graded compared to Gleason 8-10.
Also Bastian et.al.
A 1/3 of men with biopsy GS 8-10, may actually have less aggressive disease.

6. Outcomes of High Risk Localised CaP-RRP Pathological Outcomes
Study
No.
pT3
SVI
Lymph node mets
Positive
margins
Donohue et.al.
(MSKCC)
238
33%
27%
20%
32%
Mian et.al.
(MD Andersen)
188
24% 9% 6%
Manoharen et.al
(Uni Miami) 79
43%
29% 2%
46%
Serni et.al.
(Uni of Florence)
116
39%
15%

7. Outcomes of High Risk Localised CaP-RRP
Study
No.
5 yr BFS
10 yr BFS
Donohue et.al. (MSKCC)
238
51%
39%
Mian et.al. (MD Andersen)
188
71%
55%
(7 years)
Manoharen et.al (Uni Miami) 79
68%
Serni et.al. (Uni of Florence)
116
78%

8. Outcomes of High Risk Localised CaP-RRP
Mian et.al.
Organ confined disease has good outcome

9. High Risk Localised CaP-RRP
All patients
453 Patients
Henry Ford Health System
All Prostate cancer- Gleason Score >7
Analyses survival
Propensity score analysis
Surgery is better for all co-morbidities.
Median OS
RRP: 9.7 yrs
RT: 6.7 yrs
Cons: 5.2yrs
Low Charlson Score
High Charlson Score

10. Disease Specific Survival
SEER database of prostate Cancer Treatments
Population based approach.
9965 with Localised Gleason Score 8-10 prostate Cancer
Treatment
No.
10 year
%DSS (95%CI)
Radical Prostatectomy
4154
76 (71-80)
Radiation Therapy
2977
52 (46-57)
Watchful Waiting
2834
43 (38-48)
Lu et.al.

11. Multimodality Therapy Neoadjuvant Hormone Therapy
Cytoreduction (2 trials with 3 month NHT)
More organ confine disease
Fewer positive margins
No PSA PFS benefit.
(Not powered for it, not enriched with high risk)
Klotz et.al. did find PSA prgression benefit for men with PSA>20ng/ml.
Neoadjuvant Chemo
Small phase II trials only
No PSA progression or survival advantage
Ongoing CALGB trial of Docetaxel and Estramustin.

12. Adjuvant Radiation 2 Randomised Trials of higher risk
Biochemical PFS
2 Randomised Trials of higher risk
Patients randomised to observation
or adjuvant XRT
Eligible patients were:
SM+, ECE, SVI
Results:
BPFS and clinical progression
were significantly lower in XRT
No survival benefit demonstrated
No data on adjuvant vs EARLY
Salvage XRT
Bolla Et.al.
Hazard Ratio for XRT treatment
SVI: SM
ECE 0.50

13. Adjuvant Hormone Therapy
EPC studies
150 mg Bicalutamide
3 randomised studies through the world.
Significant PSA PFS if 150 mg Bicalutamide added after RRP for lacally advanced or high risk CaP.
No difference with localised CaP
Survival is not altered.
Risk Group
No.
HR (95% CI)
Locally advanced
1719
0.42 ( ) N+ 74
0.11 ( )
GS 7-10
1959
0.48 ( )
PSA>10ng/ml
1636
0.40 ( )

14. Adjuvant Chemotherapy
Adjuvant Taxotere +LHRH in High risk CaP after RRP
Closed- poor accrual
Adjuvant Taxotere following High risk CaP after RRP- VA study
Accruing.

15. Locally Advanced Prostate Cancer
176 with cT3 CaP
Pathology
Down staging is common.
24% pathological down staging (pT2)with monotherapy
41% with NHT
Stage
PSA
Gleason Score
T3a (85%)
SVI (15%)
Median (12.7ng/ml)
25% (2.6ng/ml)
75% (26ng/ml)
<6 (47%)
7 (38%)
8-10 (15%)
Organ Confined
ECE
SVI
LNI
SM+
30%
61%
34%
19%
27%

16. Locally Advanced Prostate Cancer
BCR
Death
48%
44%
24%
15% 6%
Median follow up 4.6 years.
77% with BCR Tx with HT
Clinical failure only in 36% of BCR.
10 year freedom from clinical failure= 76%

17. Locally Advanced Prostate Cancer Results From Other Centers-Monotherapy
Study
Selection
No.
5 yr CSS
10yr CSS
5 yrs OS
10 yr OS
Carver et.al.
All
176
94%
85%
88%
75%
Gerber et.al
345
57%
GS<7
73%
GS 7
67%
Van Den Oouden et.al.
GS<8 83
72%
60%
Gontero et.al 51
93%
76%

18. Morbidity of RRP for advanced disease No Worse Than clinically Localised Disease
Outcome
Clinically OC (n=152)
Locally Advanced (n=51)
Sig
Transfusion (mean per Pt)
2.5 1
0.02
OT time (min)
140
168
0.001
Lymphocele % 3 12
0.04
Bladder Neck Contracture % 18 27
0.21
Full continence
78%
80%
0.91
Severe incontinence
10%
16%
0.2
Gontero et.al.

19. The Value of Extended Lymphadenectomy In High Risk Disease.
Nomograms have limited use.
CT and MRI only sensitive in 10-30%
Sentinal node biopsy with radiolabelling and gamma probe has problems
Unable to detect nodes in area unexplored.
SPECT imaging after intraprostatic injection under evaluation.
high resolution MRI with lymphotrophic superpara-magentic nanoparticles has promise but not routinely available.

20. Heidenreich et.al reported ePLND detects 24% vs 12% positive LNs.
Wowroshek et.al. gain an additional 35% LN+ pts with ePLND.
Studer et.al. 24% LN+ with ePLND.
58% along Internal I Artery
19% only in IIA

21. ePLND is therapuetic All patients LN- Patients
Konety et.all (SEER Data
All patients who have greater than 4 LN removed benefit.
Similar Result observed by MSKCC series

22. RRP is adequate for High Risk Cancer
Better with Organ confined
Low PSA
ePLND
SM-
Locally Advanced
Better with lower GS
Lower PSA

23. Surgery+ Hormones vs XRT+Hormones
79%
89%
Messing et.al Bolla et.al
N=91 LN+ after RRP High Risk (GS>8 or pT3)

24. 5yrs CSS of all patients with LN+ was 74%
BCR
CSS