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Is Radical Prostatectomy Adequate For High Risk Prostate Cancer?

Is Radical Prostatectomy Adequate For High Risk Prostate Cancer?. Dr Manish Patel 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

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Is Radical Prostatectomy Adequate For High Risk Prostate Cancer?

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  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 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 CancerDown 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

  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 LocalisedCaP-RRP Pathological Outcomes

  7. Outcomes of High Risk LocalisedCaP-RRP

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

  9. High Risk LocalisedCaP-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 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 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 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.

  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

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

  17. Locally Advanced Prostate CancerResults From Other Centers-Monotherapy

  18. Morbidity of RRP for advanced diseaseNo Worse Than clinically Localised Disease 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 who have greater than 4 LN removed benefit. • Similar Result observed by MSKCC series All patients LN- Patients Konety et.all (SEER Data

  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 vsXRT+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

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