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Radical Nephrectomy The Role Of Surgery In mRCC

Radical Nephrectomy The Role Of Surgery In mRCC Peter Mulders Professor and Chairman Department of Urology University Medical Center Nijmegen The Netherlands Renal Cell Carcinoma General Aspects RCC accounts for 3% of all adult tumors 100.000 deaths from RCC every year worldwide

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Radical Nephrectomy The Role Of Surgery In mRCC

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  1. Radical NephrectomyThe Role Of Surgery In mRCC PeterMulders ProfessorandChairmanDepartmentofUrologyUniversityMedicalCenterNijmegen TheNetherlands

  2. Renal Cell CarcinomaGeneral Aspects • RCC accounts for 3% of all adult tumors • 100.000 deaths from RCC every year worldwide • Most aggressive GU tumor Banff, Januari 26-28th 2006

  3. Renal Cell CarcinomaGeneral Aspects • 54 % of cases present with localized disease* • 70 % are not cured by surgery alone * SEER data Banff, Januari 26-28th 2006

  4. Renal Cell CarcinomaSurgical Aspects • Surgery is the primary curative treatment in RCC Changing techniques: From open radical tumor nephrectomy to laparoscopic partial nephrectomy Banff, Januari 26-28th 2006

  5. Renal Cell CarcinomaSurgical Aspects • Robsons radical tumor nephrectomy • No-touch procedure • Total nephrectomy and adrenalectomy • Lymphadenectomy Banff, Januari 26-28th 2006

  6. Renal Cell CarcinomaSurgical Aspects • Partial nephrectomy: similar oncological outcome in <4 cm tumors • Laparoscopic (partial) nephrectomy feasible Banff, Januari 26-28th 2006

  7. Prospective Randomised Study Open vs Laparoscopic Nephrectomy (n=160) Banff, Januari 26-28th 2006

  8. Prospective Randomised Study Open vs Laparoscopic Nephrectomy Banff, Januari 26-28th 2006

  9. Conclusions LIDO-trial • Laparoscopicnephrectomy: • Safeandeffective • Similaroncologicalresults • Quickrecovery • BetterQoL • Quickerrecoveryforinitiatingsystemictherapy Banff, Januari 26-28th 2006

  10. Renal Cell Carcinoma • 5 year survival*: • 89% for localized disease • 61% for locally advanced disease • 9% for metastatic disease *SEER data Banff, Januari 26-28th 2006

  11. Renal Cell CarcinomaRisk Factors • Conventional risk factors • ECOG Performance Status • Tumor stage • Tumor grade • Microvessel density • Histological subtype • Histological tumor necrosis • Molecular markers • Cytogenetics • Proliferation and anti-apoptosis markers • Hypoxia-inducible pathway • Cell adhesion, cell motility and invasion markers Banff, Januari 26-28th 2006

  12. Renal Cell CarcinomaRisk Groups pT3a Banff, Januari 26-28th 2006

  13. Renal Cell CarcinomaRisk Factors • Combinations* • T • Grade • PS *Han K J Urol 2003;170:222 Banff, Januari 26-28th 2006

  14. Risk Group Assessment in RCC After NephrectomyZisman A JCO 2002;20:4559 Banff, Januari 26-28th 2006

  15. Renal Cell Carcinoma Risk Factors(Han K J Urol) Banff, Januari 26-28th 2006

  16. Prognosis And Surgery Of Renal Cell Carcinoma With Extension Into The Caval Wall

  17. Surgery for RCC with Caval Thrombus cavathrombus Banff, Januari 26-28th 2006

  18. cavathrombus

  19. Risk FactorsVascular invasion: T3c • Vena cava involvement: if completely resected probably no risk factor • N=44 • 27 T2N0 • 69 % 5y (mobile thrombus) • 25 % 5y (VC wall involvement) • 57 % 5y (VC wall resected) • WHO 2002: pT3c: tumor extension into vena cava above the diaphragm is a poor prognostic sign Hatcher et al J Urol1991 Lam et al J Urol 2005 Banff, Januari 26-28th 2006

  20. Risk FactorsMicroscopic Vascular Invasion* • Retrospective analysis of 180 patients • 129 no vascular invasion • 94% NED med FU 160 months • 51 microscopic vascular invasion • 39% progresion med FU 79 months This observation is not yet confirmed as an independent prognostic factor by others nor in a prospective randomised study Van Poppel J Urol 1997;158:45 Banff, Januari 26-28th 2006

  21. Renal Cell CarcinomaHistological Subtypes (WHO 2004) • Clear cell (80%) • Synonym: common or conventional • In 85% of cases associated with mutations in the VHL gene • Papillary tumor (10%) • Chromophobe tumors (4%) • Multilocular cystic clear cell (5%) Banff, Januari 26-28th 2006

  22. RCC Associated Antigen G250/MN/CAIX • Present in >85% of all RCC, 99% of the clear-cell subtype • No expression in normal kidney Mulders et al, J Urol 2006: Mab G250 has clinical efficacy in mRCC patients Banff, Januari 26-28th 2006

  23. Association of CAIX Staining and Pathologic Predictive Group and Response to IL-2 Therapy Banff, Januari 26-28th 2006

  24. Survival Curves for Patients In Good and Poor Predictive Groups. Banff, Januari 26-28th 2006

  25. Adjuvant Therapy After Nephrectomy in RCC • Aspecific immunotherapy • IFN, IL2, Combination • Tumor vaccine • Modified tumor cells • HSP • G250 Mab • Angiogenesis inhibitors Randomised studies

  26. RCC Adjuvant Interferon Alfa-NL Overall Survival Messing E et al. JCO 2003;21:1214 Banff, Januari 26-28th 2006

  27. RCC Adjuvant High Dose Bolus IL-2* DF survival Overall survival Clark J et al JCO 2003;21:3133 Banff, Januari 26-28th 2006

  28. RCC Adjuvant Autologous Tumour Vaccine* • Randomised study • N= 558 • 553 included • 276 vaccine group • 177 treated (PT2-3b, N0-3,M0) • 277 control group • 202 Jocham D et al. Lancet 2004;363:594 Banff, Januari 26-28th 2006

  29. RCC Adjuvant Autologous Tumour Vaccine* • Well balanced for risk factors (T, Grade, histology, N etc) • 5 y PFS 77.4% versus 67.8 % (p=0.0204) • T2: 81.3% versus 74.6% (n=264) (NS) • T3: 67.5% versus 49.7% (n=115) (p=0.039) • Median time to progression not reached • Overall survival not given Jocham D et al. Lancet 2004;363:594 Banff, Januari 26-28th 2006

  30. RCC Adjuvant • No standard treatment. • The results of several studies are not available yet. • Adjuvant treatment should only be given in the frame work of clinical studies Banff, Januari 26-28th 2006

  31. mRCCThe Role of Tumor Nephrectomy Two prospective randomised studies performed to address this issue • SWOG • EORTC Banff, Januari 26-28th 2006

  32. EORTC

  33. mRCCThe Role of Tumor Nephrectomy • FlaniganNEJM2001SWOG:246ptn RNx+IFN2bIFNa2b n120(92)121(83) CR/PR0/33.3%1/23.6% mOS(m)118(p=0.05) • MickischLancet2001EORTC;85ptn mOS(m)1811(p<0.05) • CombinedanalysisJUrol2004;171(3):1071-6 mOS13.67.8m(p<0.05) Banff, Januari 26-28th 2006

  34. Take Home Messages • Prognostic factors and risk group formation should be regarded and implemented in treatment decision • Surgery is the only chance for cure in localized disease • Surgery can be minimal invasive with similar oncological outcome • Surgery in combination with Interferon-alpha gives survival benefit BUT Banff, Januari 26-28th 2006

  35. What is the exact role of surgery in the era of angiogenesis inhibitors? What is the exact place of angiogenesis inhibitors in patient who undergo surgery?

  36. Unaddressed Questions • What is the role of tumor nephrectomy in combination with anti-angiogenesis ? • What is the best timing of nephrectomy ? • What is the effect on the primary tumor? • Will anti-angiogensis treatment in an adjuvant setting give benifit • ? Banff, Januari 26-28th 2006

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