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Radical Nephrectomy The Role Of Surgery In mRCC

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Title: Radical Nephrectomy The Role Of Surgery In mRCC


1
Radical NephrectomyThe Role Of Surgery In mRCC
  • Peter Mulders
  • Professor and Chairman Department of Urology
    University Medical Center Nijmegen
  • The Netherlands

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

3
Renal Cell CarcinomaGeneral Aspects
  • 54 of cases present with localized disease
  • 70 are not cured by surgery alone

SEER data
4
Renal Cell CarcinomaSurgical Aspects
  • Surgery is the primary curative treatment in RCC
  • Changing techniques
  • From open radical tumor nephrectomy
  • to laparoscopic partial nephrectomy

5
Renal Cell CarcinomaSurgical Aspects
  • Robsons radical tumor nephrectomy
  • No-touch procedure
  • Total nephrectomy and adrenalectomy
  • Lymphadenectomy

6
Renal Cell CarcinomaSurgical Aspects
  • Partial nephrectomy similar oncological outcome
    in lt4 cm tumors
  • Laparoscopic (partial) nephrectomy feasible

7
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8
Prospective Randomised Study Open vs Laparoscopic
Nephrectomy (n160)
9
Prospective Randomised Study Open vs Laparoscopic
Nephrectomy
10
Conclusions LIDO-trial
  • Laparoscopic nephrectomy
  • Safe and effective
  • Similar oncological results
  • Quick recovery
  • Better QoL
  • Quicker recovery for initiating systemic
    therapy

11
Renal Cell Carcinoma
  • 5 year survival
  • 89 for localized disease
  • 61 for locally advanced disease
  • 9 for metastatic disease

SEER data
12
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

13
Renal Cell CarcinomaRisk Groups pT3a
14
Renal Cell CarcinomaRisk Factors
  • Combinations
  • T
  • Grade
  • PS

Han K J Urol 2003170222
15
Risk Group Assessment in RCC After
NephrectomyZisman A JCO 2002204559
16
Renal Cell Carcinoma Risk Factors(Han K J Urol)
17
  • Prognosis And Surgery Of Renal Cell Carcinoma
    With Extension Into The Caval Wall

18
Surgery for RCC with Caval Thrombus
cavathrombus
19
cavathrombus
20
Risk FactorsVascular invasion T3c
  • Vena cava involvement if completely resected
    probably no risk factor
  • N44
  • 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
21
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 199715845
22
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)

23
RCC Associated Antigen G250/MN/CAIX
  • Present in gt85 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
24
Association of CAIX Staining and Pathologic
Predictive Group and Response to IL-2 Therapy
25
Survival Curves for Patients In Good and Poor
Predictive Groups.
26
Adjuvant Therapy After Nephrectomy in RCC
  • Randomised studies
  • Aspecific immunotherapy
  • IFN, IL2, Combination
  • Tumor vaccine
  • Modified tumor cells
  • HSP
  • G250 Mab
  • Angiogenesis inhibitors

27
RCC Adjuvant Interferon Alfa-NL Overall Survival
Messing E et al. JCO 2003211214
28
RCC Adjuvant High Dose Bolus IL-2
DF survival
Overall survival
Clark J et al JCO 2003213133
29
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 2004363594
30
RCC Adjuvant Autologous Tumour Vaccine
  • Well balanced for risk factors (T, Grade,
    histology, N etc)
  • 5 y PFS 77.4 versus 67.8 (p0.0204)
  • T2 81.3 versus 74.6 (n264) (NS)
  • T3 67.5 versus 49.7 (n115) (p0.039)
  • Median time to progression not reached
  • Overall survival not given

Jocham D et al. Lancet 2004363594
31
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

32
mRCCThe Role of Tumor Nephrectomy
  • Two prospective randomised studies performed to
    address this issue
  • SWOG
  • EORTC

33
EORTC
34
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35
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36
mRCCThe Role of Tumor Nephrectomy
  • Flanigan NEJM 2001 SWOG 246 ptn
  • R Nx IFN?2b IFNa2b
  • n 120(92) 121(83)
  • CR/PR 0/3 3.3 1/2 3.6
  • mOS(m) 11 8 (p0.05)
  • Mickisch Lancet 2001 EORTC 85 ptn
  • mOS (m) 18 11 (plt0.05)
  • Combined analysis J Urol 2004171(3)1071-6
  • mOS 13.6 7.8 m (plt0.05)

37
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


38
  • 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?

39
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
  • ?
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