Presentation on theme: "Is Radical Prostatectomy Adequate For High Risk Prostate Cancer?"— Presentation transcript:
1Is Radical Prostatectomy Adequate For High Risk Prostate Cancer? Dr Manish PatelUrological Cancer SurgeonWestmead HospitalUniversity of Sydney
2What 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
3Guidelines EAU AUA NCCN 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.NCCNFor: cT3a or Gleason 8-10 or PSA>20ng/mlRadical prostatectomy (selected patients with no fixation, low volume, + plevic lymph node dissection.)ADT + XRT (3 years)
4High 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 gradingGrossfeld et.al. -38% down grading
5High 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.
6Outcomes of High Risk Localised CaP-RRP Pathological Outcomes StudyNo.pT3SVILymph node metsPositivemarginsDonohue et.al.(MSKCC)23833%27%20%32%Mian et.al.(MD Andersen)18824%9%6%Manoharen et.al(Uni Miami)7943%29%2%46%Serni et.al.(Uni of Florence)11639%15%
7Outcomes of High Risk Localised CaP-RRP StudyNo.5 yr BFS10 yr BFSDonohue et.al. (MSKCC)23851%39%Mian et.al. (MD Andersen)18871%55%(7 years)Manoharen et.al (Uni Miami)7968%Serni et.al. (Uni of Florence)11678%
8Outcomes of High Risk Localised CaP-RRP Mian et.al.Organ confined disease has good outcome
9High Risk Localised CaP-RRP All patients453 PatientsHenry Ford Health SystemAll Prostate cancer- Gleason Score >7Analyses survivalPropensity score analysisSurgery is better for all co-morbidities.Median OSRRP: 9.7 yrsRT: 6.7 yrsCons: 5.2yrsLow Charlson ScoreHigh Charlson Score
10Disease Specific Survival SEER database of prostate Cancer TreatmentsPopulation based approach.9965 with Localised Gleason Score 8-10 prostate CancerTreatmentNo.10 year%DSS (95%CI)Radical Prostatectomy415476 (71-80)Radiation Therapy297752 (46-57)Watchful Waiting283443 (38-48)Lu et.al.
11Multimodality Therapy Neoadjuvant Hormone Therapy Cytoreduction (2 trials with 3 month NHT)More organ confine diseaseFewer positive marginsNo 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 ChemoSmall phase II trials onlyNo PSA progression or survival advantageOngoing CALGB trial of Docetaxel and Estramustin.
12Adjuvant Radiation 2 Randomised Trials of higher risk Biochemical PFS2 Randomised Trials of higher riskPatients randomised to observationor adjuvant XRTEligible patients were:SM+, ECE, SVIResults:BPFS and clinical progressionwere significantly lower in XRTNo survival benefit demonstratedNo data on adjuvant vs EARLYSalvage XRTBolla Et.al.Hazard Ratio for XRT treatmentSVI:SMECE 0.50
13Adjuvant Hormone Therapy EPC studies150 mg Bicalutamide3 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 CaPSurvival is not altered.Risk GroupNo.HR (95% CI)Locally advanced17190.42 ( )N+740.11 ( )GS 7-1019590.48 ( )PSA>10ng/ml16360.40 ( )
14Adjuvant Chemotherapy Adjuvant Taxotere +LHRH in High risk CaP after RRPClosed- poor accrualAdjuvant Taxotere following High risk CaP after RRP- VA studyAccruing.
15Locally Advanced Prostate Cancer 176 with cT3 CaPPathologyDown staging is common.24% pathological down staging (pT2)with monotherapy41% with NHTStagePSAGleason ScoreT3a (85%)SVI (15%)Median (12.7ng/ml)25% (2.6ng/ml)75% (26ng/ml)<6 (47%)7 (38%)8-10 (15%)Organ ConfinedECESVILNISM+30%61%34%19%27%
16Locally Advanced Prostate Cancer BCRDeath48%44%24%15%6%Median follow up 4.6 years.77% with BCR Tx with HTClinical failure only in 36% of BCR.10 year freedom from clinical failure= 76%
17Locally Advanced Prostate Cancer Results From Other Centers-Monotherapy StudySelectionNo.5 yr CSS10yr CSS5 yrs OS10 yr OSCarver et.al.All17694%85%88%75%Gerber et.al34557%GS<773%GS 767%Van Den Oouden et.al.GS<88372%60%Gontero et.al5193%76%
18Morbidity of RRP for advanced disease No Worse Than clinically Localised Disease OutcomeClinically OC (n=152)Locally Advanced (n=51)SigTransfusion (mean per Pt)2.510.02OT time (min)1401680.001Lymphocele %3120.04Bladder Neck Contracture %18270.21Full continence78%80%0.91Severe incontinence10%16%0.2Gontero et.al.
19The 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 problemsUnable 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.
20Heidenreich 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 Artery19% only in IIA
21ePLND is therapuetic All patients LN- Patients Konety et.all (SEER DataAll patients who have greater than 4 LN removed benefit.Similar Result observed by MSKCC series
22RRP is adequate for High Risk Cancer Better with Organ confinedLow PSAePLNDSM-Locally AdvancedBetter with lower GSLower PSA
23Surgery+ Hormones vs XRT+Hormones 79%89%Messing et.al Bolla et.alN=91 LN+ after RRP High Risk (GS>8 or pT3)
245yrs CSS of all patients with LN+ was 74% BCRCSS