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Surgical Treatment of Locally Advanced PCa

Surgical Treatment of Locally Advanced PCa. Bertrand Guillonneau, MD, PhD, dr hc Chief, service of urology, DCSS, Paris, France. Surgery and Locally Advanced PCa. Which definition for LAPCa ? How to diagnose before treatment? Rationale for surgery?

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Surgical Treatment of Locally Advanced PCa

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  1. Surgical Treatment of Locally Advanced PCa Bertrand Guillonneau, MD, PhD, dr hc Chief, service of urology, DCSS, Paris, France

  2. Surgery and Locally Advanced PCa Which definition for LAPCa ? How to diagnose before treatment? Rationale for surgery? What are the criteria for surgical quality? What are the surgical results? Could surgery be sufficient?

  3. Definitions Locally Advanced PCa: pT3ab pN0 M0 <pT4 pN1 M0 Excluding pT4 & pTx Nx M1 But this definition is very and too much heterogeneous: all pT3a are not identical all pT3b are not identical all pN1 are not identical but all are at “high risk” of recurrence

  4. Definitions “High Risk PCa” have a wide definition: 1) PBx Gleason score 8+ 2) preop PSA. >20+ 3) TNM stade cT3+ 4) PSA>=20 or cT2c+ or PBx Gleason score 8+ 5) Recurrence free survival < 70% 6) PSA >=20 or cT3+ or BPxGleason score 8+ These definition vary over time but not all “high risk Pca” are LAPCa: 22% are pT2N0 @ DCSS 1. Foassati et al, BJU., 2015, in press

  5. High Risk PCa BCR-free survival Yossepovitch O. et al, J Urol., 2007, 179, 493-9

  6. High Risk PCa BCR-free survival Yossepovitch et al, J Urol, 2007, 179: 493-9

  7. High Risk PCa BCR-free survival Yossepovitch et al, J Urol, 2007, 179: 493-9

  8. Are Intermediate risk PCa different? Intermediate risk PCa with +BxP core >4/12 vs High risk PCa 2017 DCSS, in progress

  9. Specific definition of High Risk PCa has little impact on BCR free survival Carvell T et al, J Urol, 2009, 181: 75-80

  10. Mortality Risks Akre et al, Eur Urol., 2011, 60: 555-63

  11. Pre-treatment diagnosis of LAPCa Based on: Clinical Stage: 43.8% patients considered as cT3 are ultimately pT2 1 PSA - level - kinetics ? PBx - Gleason score - Ratio Pos. / Neg. cores - Infiltration / length by core - Ratio cancer length / core length Negative Bone Scan 1.Van Poppel et al, Eur J Cancer, 2006,42: 1062-67

  12. Pre-treatment diagnosis of LAPCa What are the roles of: pMRI PET- CT, choline, PSMA Proteinomics? Genomic? CTC?

  13. MRI Diagnostic of LAPCa Review of 75 studies, 9796 patients : Sensitivity (95%CI) Specificity (95%CI) ECE 0.57 (0.49-0.64) 0.91 (0.88-0.93) SVI 0.58 (0.47-0.68) 0.96 (0.95-0.97) overall T3 0.61 (0.54-0.67) 0.88 (0.85-0.91) De Rooij et al, Eur Urol, 2015,

  14. Rational for Surgery 1. Lower local complications related to the tumor Retention Hematuria Bladder infiltration Ureteral infiltration Rectal infiltration

  15. Surgery increases both Overal & Specific Survival Zelefski et al, JCO, 2010, 28: 1508-13

  16. Surgery increases both Overal & Specific Survival Zelefski et al, JCO, 2010, 28: 1508-13

  17. Surgery increases both Overal & Specific Survival Zelefski et al, JCO, 2010, 28: 1508-13

  18. Surgery impacts on tumour itself Kim. et al, Cell., 2009, 139: 1315-26

  19. Surgical Quality 1. Surgical Approach 2. Pelvic Lymph node dissection 3. Surgical Margins

  20. Surgical Route: no impact PSA>=20, cT2C+ ou BPxGleason grade 8+

  21. Pelvic Lymph Node Dissection

  22. Surgical Results @ DCSS PLND performed for MSKCC nomogram N+ > 2% Nber Nodes: median = 12; mean= 13

  23. LNI & LAPCa @ DCSS 2017 DCSS, in progress

  24. Long term survival of pN+ patients treated by surgery (PLND & RP) alone Touijer et al, EurUrol, 2014, 65:20-5

  25. Long term survival of pN+ patients treated by surgery (PLND & RP) alone Touijer et al, EurUrol, 2014, 65:20-5

  26. Surgical Results @ DCSS 2017 DCSS, in progress

  27. Long term survival of pN+ patients treated by surgery (PLND & RP) alone Touijer et al, Eur Urol, 2014, 65:20-5

  28. Positive SM is associated with PCa Specific Mortality Wright et al, JUrol, 2010, 183: 2213-18

  29. Positive SM is associated with PCa Specific Mortality Wright et al, JUrol, 2010, 183: 2213-18

  30. Is Surgery enough? • Role of adjuvant EBRT? • Role of adjuvant + HT? • Role of adjuvant or neoadjyuvant medical treatment ? • For which sub-population is Surgery like to be curative?

  31. Surgery + Adjuvant EBRT Patients pT2-4 pN+ M0 Briganti et al, Eur Urol, 2011, 59: 832-40

  32. Surgery + Adjuvant EBRT 536 pT3aN0/NX R1 with the required follow-up data Karl et al, Radiot Oncol, 2015, 116: 119-24

  33. Surgery + Neo Adjuvant HT Long term FU of neo-adjuvant 3-month HT Randomized Study : Yee, BJU, 2010, 105: 185-90

  34. Neo-adjuvant therapy + Surgery 1. A Phase 2 Open-Label, Randomized, Multi-center Study of Neoadjuvant Abiraterone Acetate (CB7630) Plus Leuprolide Acetate and Prednisone Versus Leuprolide Acetate Alone in Men With Localized High Risk Prostate Cancer.(NCT00924469) Closed, March 2012 Primary Outcome Measures: Testosterone Concentration in Prostate Tissue …/… 2. A Randomized, Open-Label, Phase 2 Study of MDV3100 as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer (NCT01547299) Primary Outcome Measures: Pathologic Complete Response Rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]Pathologic complete response rate following triplet therapy (enzalutamide in combination with leuprolide and dutasteride) and enzalutamide alone when administered as neoadjuvant therapy for 6 months prior to prostatectomy in patients with localized prostate cancer. Pathologic complete response is defined as the absence of morphologically identifiable carcinoma in the prostatectomy specimen, as evaluated by the site pathologist using standard methods …/…

  35. In conclusion Surgery has a key role Quality of Surgery is essential Curative role of PLND Local control: NEG. S margins Surgery can not do all Multidisciplinary approach to be refined Accurate definition is mandatory Pre-treatment evaluation is still not accurate

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