Presentation on theme: "Is Radical Prostatectomy Adequate For High Risk Prostate Cancer? Dr Manish Patel Urological Cancer Surgeon Urological Cancer Surgeon Westmead Hospital."— Presentation transcript:
Is Radical Prostatectomy Adequate For High Risk Prostate Cancer? Dr Manish Patel Urological Cancer Surgeon Urological Cancer Surgeon Westmead Hospital University of Sydney
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
Guidelines 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. 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) EAU AUA NCCN
High Risk- Localised Prostate Cancer Down 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 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.A 1/3 of men with biopsy GS 8-10, may actually have less aggressive disease.
Outcomes of High Risk Localised CaP-RRP StudyNo.5 yr BFS10 yr BFS Donohue 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%
Mian et.al. Organ confined disease has good outcome Outcomes of High Risk Localised CaP-RRP
High Risk Localised CaP-RRP All patients Low Charlson Score High Charlson Score 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
Disease Specific Survival TreatmentNo.10 year %DSS (95%CI) Radical Prostatectomy415476 (71-80) Radiation Therapy297752 (46-57) Watchful Waiting283443 (38-48) SEER database of prostate Cancer Treatments Population based approach. 9965 with Localised Gleason Score 8-10 prostate Cancer Lu et.al.
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.
Adjuvant 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 treatment SVI: 0.48 SM+0.40 ECE0.50
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 GroupNo.HR (95% CI) Locally advanced17190.42 (0.35-0.50) N+740.11 (0.04- 0.30) GS 7-1019590.48 (0.40-0.58) PSA>10ng/ml16360.40 (0.33-0.49)
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.
Locally Advanced Prostate Cancer 176 with cT3 CaP Pathology Down staging is common. 24% pathological down staging (pT2)with monotherapy 41% with NHT StagePSAGleason 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 ECESVILNISM+ 30%61%34%19%27%
Clinical failure only in 36% of BCR. 10 year freedom from clinical failure= 76% Locally Advanced Prostate Cancer 48% 44% 6% 15% 24% BCRDeath Median follow up 4.6 years. 77% with BCR Tx with HT
StudySelectionNo.5 yr CSS10yr CSS 5 yrs OS10 yr OS Carver et.al.All17694%85%88%75% Gerber et.alAll34557% GS<773% GS 767% Van Den Oouden et.al. GS<88385%72%75%60% Gontero et.alAll5193%76% Locally Advanced Prostate Cancer Results From Other Centers-Monotherapy
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) 2.510.02 OT time (min) 1401680.001 Lymphocele % 3120.04 Bladder Neck Contracture % 18270.21 Full continence 78%80%0.91 Severe incontinence 10%16%0.2 Gontero et.al.
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.
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 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 Cancer High Risk Better with Organ confined Low PSA ePLND SM- Locally Advanced Better with lower GS Lower PSA
Surgery+ Hormones vs XRT+Hormones Messing et.al. Bolla et.al N=91 LN+ after RRP High Risk (GS>8 or pT3) 89% 79%
5yrs CSS of all patients with LN+ was 74% BCR CSS