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Is Radical Prostatectomy Is Radical Prostatectomy Adequate For High Risk Prostate Adequate For High Risk Prostate
Cancer?Cancer?
Dr Manish PatelDr Manish Patel Urological Cancer Surgeon Urological Cancer Surgeon
Westmead HospitalWestmead HospitalUniversity of SydneyUniversity of Sydney
What is High RiskWhat is High RiskHigh 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
GuidelinesGuidelines
Option: Although active surveillance, interstitial prostate brachytherapy, externalbeam radiotherapy, and radical prostatectomy are options for the management ofpatients with high-risk localized prostate cancer, recurrence rates are high.
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)
EAUEAU
AUA
NCCN
High Risk- Localised Prostate CancerHigh Risk- Localised Prostate CancerDown Grading is CommonDown Grading is Common
Donohue et.al. –MSKCC
238 Men had biopsy Gleason score 8-10.
45% had Gleason score <7 in prostate specimen.
Manoharan et.al- 31% down grading
Grossfeld et.al. -38% down grading
High Risk- Localised Prostate CancerHigh 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 A 1/3 of men with biopsy GS 8-10, may biopsy GS 8-10, may actually have less actually have less aggressive disease.aggressive disease.
Outcomes of High Risk Localised CaP-RRPOutcomes of High Risk Localised CaP-RRPPathological OutcomesPathological 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%
Outcomes of High Risk Localised CaP-RRPOutcomes 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%
• Mian et.al.
Organ confined disease has good outcome
Outcomes of High Risk Localised CaP-RRPOutcomes of High Risk Localised CaP-RRP
High Risk Localised CaP-RRPHigh Risk Localised CaP-RRP
All patients
Low Charlson Score
High Charlson Score
453 PatientsHenry Ford Health SystemAll Prostate cancer- Gleason Score >7Analyses survivalPropensity score analysis
Surgery is better for all co-morbidities.Median OSRRP: 9.7 yrsRT: 6.7 yrsCons: 5.2yrs
Disease Specific SurvivalDisease Specific Survival
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)
SEER database of prostate Cancer TreatmentsPopulation based approach.9965 with Localised Gleason Score 8-10 prostate Cancer
Lu et.al.
Multimodality TherapyMultimodality TherapyNeoadjuvant Hormone 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 PSA>20ng/ml.
Neoadjuvant Chemo
• Small phase II trials only
• No PSA progression or survival advantage
• Ongoing CALGB trial of Docetaxel and Estramustin.
Adjuvant RadiationAdjuvant Radiation
Bolla Et.al.
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
Hazard Ratio for XRT treatmentSVI: 0.48SM+ 0.40ECE 0.50
Adjuvant Hormone TherapyAdjuvant 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)
PSA>10ng/ml 1636 0.40 (0.33-0.49)
Adjuvant ChemotherapyAdjuvant Chemotherapy• Adjuvant Taxotere +LHRH in High risk CaP after RRP
– Closed- poor accrual
• Adjuvant Taxotere following High risk CaP after RRP- VA study
– Accruing.
Locally Advanced Prostate CancerLocally Advanced Prostate Cancer
176 with cT3 CaP
Pathology
Down staging is common.24% pathological down staging (pT2)with monotherapy41% 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%
• Clinical failure only in 36% of BCR.
• 10 year freedom from clinical failure= 76%
Locally Advanced Prostate CancerLocally Advanced Prostate Cancer
48%44%
6%15%
24%
BCR Death
•Median follow up 4.6 years.•77% with BCR Tx with HT
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%
GS<7 73%
GS 7 67%
Van Den Oouden et.al.
GS<8 83 85% 72% 75% 60%
Gontero et.al All 51 93% 76%
Locally Advanced Prostate CancerLocally Advanced Prostate CancerResults From Other Centers-MonotherapyResults From Other Centers-Monotherapy
Morbidity of RRP for advanced diseaseMorbidity of RRP for advanced diseaseNo Worse Than clinically Localised DiseaseNo 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.
The Value of Extended LymphadenectomyThe Value of Extended LymphadenectomyIn High Risk Disease.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.
• 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
ePLND is therapueticePLND is therapuetic
• All patients who have greater than 4 LN removed benefit.• Similar Result observed by MSKCC series
All patients LN- Patients
Konety et.all (SEER Data
RRP is adequate for High Risk CancerRRP is adequate for High Risk Cancer• High Risk
• Better with Organ confined
• Low PSA
• ePLND
• SM-
• Locally Advanced
• Better with lower GS
• Lower PSA
Surgery+ Hormones vs XRT+HormonesSurgery+ Hormones vs XRT+Hormones
Messing et.al. Bolla et.alN=91 LN+ after RRP High Risk (GS>8 or pT3)
89%79%
• 5yrs CSS of all patients with LN+ was 74%BCR
CSS