Is Radical Prostatectomy Adequate For High Risk Prostate Cancer?

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 gt20ng/ml
• Locally Advanced
• Clinical T3
• Lymph node positive
• Excluded
• Clinical T4
• N2 or distant metastatic disease

3
Guidelines
EAU
AUA
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 PSAgt20ng/ml
• Radical prostatectomy (selected patients with no
  fixation, low volume, plevic lymph node
  dissection.)
• ADT XRT (3 years)

4
High Risk- Localised Prostate CancerDown Grading
is Common

• Donohue et.al. MSKCC
• 238 Men had biopsy Gleason score 8-10.
• 45 had Gleason score lt7 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 9
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 gt7 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 (95CI)
Radical Prostatectomy 4154 76 (71-80)
Radiation Therapy 2977 52 (46-57)
Watchful Waiting 2834 43 (38-48)
Lu et.al.
11
Multimodality TherapyNeoadjuvant 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 PSAgt20ng/ml.
• Neoadjuvant Chemo
• Small phase II trials only
• No PSA progression or survival advantage
• Ongoing CALGB trial of Docetaxel and Estramustin.

12
Adjuvant Radiation
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
0.48 SM 0.40 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 (0.35-0.50)
N 74 0.11 (0.04- 0.30)
GS 7-10 1959 0.48 (0.40-0.58)
PSAgt10ng/ml 1636 0.40 (0.33-0.49)
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) lt6 (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 CancerResults 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 All 345 57
GSlt7 73
GS 7 67
Van Den Oouden et.al. GSlt8 83 85 72 75 60
Gontero et.al All 51 93 76
18
Morbidity of RRP for advanced diseaseNo Worse
Than clinically Localised Disease
Outcome Clinically OC (n152) Locally Advanced (n51) 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 LymphadenectomyIn 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

• High Risk
• Better with Organ confined
• Low PSA
• ePLND
• SM-

• Locally Advanced
• Better with lower GS
• Lower PSA

23
Surgery Hormones vs XRTHormones
79
89
Messing et.al.
Bolla et.al N91 LN after RRP
High Risk (GSgt8
or pT3)
24

• 5yrs CSS of all patients with LN was 74

BCR
CSS
25
(No Transcript)