TRATAMIENTO ADYUVANTE A LA NEFRECTOMIA EN CÁNCER DE RIÑÓN Xavier García del Muro Solans
Nefrectomia citorreductiva
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NEFRECTOMÍA
CITOREDUCTIVA
Katherine Henríquez
UROLOGÍA
Enero 30, 2012
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NEFRECTOMÍA CITOREDUCTIVACARCINOMA DE CÉLULAS RENALES METASTÁSICO
Sobrevida RCC a 5 años 50-55%
Sobrevida con metástasis 10-20%
De los RCC diagnosticados
20% localmente avanzados
30% con metástasis
40% se les realiza nefrectomía
K.K. Aben, T.K. Luth, M.L. Janssen-Heijnen et al. No improvement in renal cell carcinoma survival: a population-based study in the Netherlands. Eur J Cancer, 44 (2008), pp. 1701–1709
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NEFRECTOMÍA CITOREDUCTIVACARCINOMA DE CÉLULAS RENALES METASTÁSICO
Sobrevida mayor
Prevención de complicaciones tumorales
Mejor respuesta a la inmunoterapia
Morbilidad y mortalidad perioperatoriamayor
Retraso del inicio de terapia blanco
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NEFRECTOMÍA CITOREDUCTIVACARCINOMA DE CÉLULAS RENALES METASTÁSICO
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NEFRECTOMÍA CITOREDUCTIVACARCINOMA DE CÉLULAS RENALES METASTÁSICO
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NEFRECTOMÍA CITOREDUCTIVACARCINOMA DE CÉLULAS RENALES METASTÁSICO
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NEFRECTOMÍA CITOREDUCTIVATERAPIA SISTÉMICA
ERA DE CITOKINAS INFα e IL2
INMUNOTERAPIA 1992 - 2004
• NEFRECTOMÍA COMO ESTÁNDAR DE TRATAMIENTO
• POSTQUIRÚRGICO / ADJUVANTE
ERA INHIBIDORES DE ANGIOGÉNESIS (TKI y
Ab VEFG) y mTOR
TERAPIA BLANCO 2005 - 2012
• ¿NEFRECTOMÍA REALMENTE ES NECESARIA?
• ¿PREQUIRUGICO? / ¿NEOADJUVANTE?
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NEFRECTOMÍA CITOREDUCTIVATUMORIGÉNESIS
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NEFRECTOMÍA CITOREDUCTIVA
POSIBLES MECANISMOS DE ACCIÓN
Reducción del volumen tumoral
Cambio del microambiente tumoral con inhibición del grado de invasión
Gatenby RA, Gawlinski ET, Tangen CM et al: The possible role of postoperative azotemia in enhancedsurvival of patients with metastatic renal cancer after cytoreductive nephrectomy. Cancer Res 2002; 62: 5218.Tatsumi T, Herrem CJ, Olson WC et al: Disease stage variation in CD4 and CD8 T-cell reactivity to the receptor tyrosinekinase EphA2 in patients with renal cell carcinoma. Cancer Res 2003; 63: 4481.Fujikawa K, Matsui Y, Miura K et al: Serum immunosuppressive acidic protein and natural killer cell activity in patientswith metastatic renal cell carcinoma before and after nephrectomy. J Urol 2000; 164: 673.
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NEFRECTOMÍA CITOREDUCTIVA
POSIBLES MECANISMOS DE ACCIÓN
Disminución de inmunosupresión, reversión de relación TH1/TH2 aumento en actividad de células NK
Disminución de marcadores angiogénicos incluyendo VEGF
Dadian G, Riches PG, Henderson DC et al: Immunological parameters in peripheral blood of patientswith renal cell carcinoma before and after nephrectomy. Br J Urol 1994; 74: 15.Klatte T, Bohm M, Nelius T et al: Evaluation of peri-operative peripheral and renal venous levels of pro- and anti-angiogenic factors and their relevance in patients with renal cell carcinoma. BJU Int 2007; 100: 209..
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NEFRECTOMÍA CITOREDUCTIVAINMUNOTERAPIA
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NEFRECTOMÍA CITOREDUCTIVAINMUNOTERAPIA
Flanigan RC, Mickisch G, Sylvester R, et al. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol 2004;171:1071.
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NEFRECTOMÍA CITOREDUCTIVAINMUNOTERAPIA
K Kwan and A Kapoor. Cytoreductive nephrectomy in metastatic renal cell carcinoma: the evolving role of surgery in the era of molecular targeted therapy. Current Opinion in Supportive and Palliative Care 2009, 3:157–165
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NEFRECTOMÍA CITOREDUCTIVATERAPIA BLANCO
314 pacientes 2004-2008, nefrectomía 201
55% Edad < 60 años
30% Karnofsky < 80
74% más de un sitio de metástasis
Sunitinib 198 (63%)
Tiempo de inicio promedio 5 meses postoperatorio
T Choueiri, W Xie, C Kollmannsberger et al. The Impact of Cytoreductive Nephrectomy on Survival ofPatients With Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor Targeted Therapy. The Journal of Urology Vol. 185, 60-66, January 2011
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NEFRECTOMÍA CITOREDUCTIVATERAPIA BLANCO
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NEFRECTOMÍA CITOREDUCTIVATERAPIA BLANCO
T Choueiri, W Xie, C Kollmannsberger et al. The Impact of Cytoreductive Nephrectomy on Survival ofPatients With Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor Targeted Therapy. The Journal of Urology Vol. 185, 60-66, January 2011
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NEFRECTOMÍA CITOREDUCTIVACONTRAINDICACIONES
Contraindicaciones RELATIVAS
Histología• Sarcomatoide• No células claras
Metástasis• Cerebral• Hepática• Ósea de gran volumen tumoral
Edad ≥ 75 años
Karnofsky < 80
E Abel and C Wood. Cytoreductive nephrectomy for metastatic RCC in the era of targeted therapy. Nat. Rev. Urol. 6, 375–383 (2009).
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NEFRECTOMÍA CITOREDUCTIVASOBREVIDA
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NEFRECTOMÍA CITOREDUCTIVASOBREVIDA
Mekhail TM, Abou-Jawde RM, BoumerhiGet al. Validation and extension of the Memorial Sloan-Ketteringprognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J ClinOncol 2005;23: 832–841.
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NEFRECTOMÍA CITOREDUCTIVASOBREVIDA
Mekhail TM, Abou-Jawde RM, BoumerhiGet al. Validation and extension of the Memorial Sloan-Ketteringprognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J ClinOncol 2005;23: 832–841.
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NEFRECTOMÍA CITOREDUCTIVAFACTORES PRONÓSTICOS
V Margulis, S Matin and C Wood. Cytoreductive nephrectomy in metastatic renal cell carcinoma. Current Opinion in Urology 2008, 18:474–480.
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NEFRECTOMÍA CITOREDUCTIVASOBREVIDA
328 pacientes entre 1999-2005 retrospectivo37.5% nefrectomía
Sobrevida a 3 años mayor con nefrectomía previa (25 vs 4%, p < 0.001) Reduce mortalidad en 50%
Nefrectomía se asocia con mejor sobrevida(RR 0.52, 95% CI 0.37–0.73)
Aben KK, Heskamp S, Janssen-Heijnen ML, Koldewijn EL, van Herpen CM, Kiemeney LA, Oosterwijk E, van Spronsen DJ. Better survival in patients with metastasised kidney cancer after nephrectomy: a population-basedstudy in the Netherlands. Eur J Cancer. 2011 Sep;47(13):2023-32.
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NEFRECTOMÍA CITOREDUCTIVAFACTORES
Aben KK, Heskamp S, Janssen-Heijnen ML, Koldewijn EL, van Herpen CM, Kiemeney LA, Oosterwijk E, van Spronsen DJ. Better survivalin patients with metastasised kidney cancer after nephrectomy: a population-based study in the Netherlands. Eur J Cancer. 2011 Sep;47(13):2023-32.
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NEFRECTOMÍA CITOREDUCTIVAFACTORES
Aben KK, Heskamp S, Janssen-Heijnen ML, Koldewijn EL, van Herpen CM, Kiemeney LA, Oosterwijk E, van Spronsen DJ. Better survivalin patients with metastasised kidney cancer after nephrectomy: a population-based study in the Netherlands. Eur J Cancer. 2011 Sep;47(13):2023-32.
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NEFRECTOMÍA CITOREDUCTIVAFACTORES
Aben KK, Heskamp S, Janssen-Heijnen ML, Koldewijn EL, van Herpen CM, Kiemeney LA, Oosterwijk E, van Spronsen DJ. Better survivalin patients with metastasised kidney cancer after nephrectomy: a population-based study in the Netherlands. Eur J Cancer. 2011 Sep;47(13):2023-32.
Baja probabilidad de nefrectomía
Pobre estado funcional (Karnofsky < 80%)
Metástasis hepática y ósea
Edad avanzada al diagnóstico(≥ 80 años)
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NEFRECTOMÍA CITOREDUCTIVASOBREVIDA
Aben KK, Heskamp S, Janssen-Heijnen ML, Koldewijn EL, van Herpen CM, Kiemeney LA, Oosterwijk E, van Spronsen DJ. Better survival in patients with metastasised kidney cancer after nephrectomy: a population-basedstudy in the Netherlands. Eur J Cancer. 2011 Sep;47(13):2023-32.
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NEFRECTOMÍA CITOREDUCTIVAEDAD
404 pacientes, 1995-2005En ≥ 75 años de edad:
Mortalidad perioperatoria mayor 21 vs 1.1%
Pérdida sanguínea y transfusión mayor
Sobrevida sin diferencias 16.6 vs 13.7 meses
Potencial significativo de morbilidad y mortalidad Expectativas realistas
A.K. Kader, P. Tamboli, T. Luongo et al. Cytoreductive nephrectomy in the elderly patient: the M.D. Anderson Cancer Center experience. J Urol, 177 (2007), pp. 855–860
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NEFRECTOMÍA CITOREDUCTIVAEDAD
A.K. Kader, P. Tamboli, T. Luongo et al. Cytoreductive nephrectomy in the elderly patient: the M.D. Anderson Cancer Center experience. J Urol, 177 (2007), pp. 855–860
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NEFRECTOMÍA CITOREDUCTIVAEDAD
504 pacientes 1998-2007 Nefrectomía en 15.4% con edad ≥ 75 años
Tasas mayores de:
Mortalidad perioperatoria 4.8 vs 1.9%
Transfusión de hemoderivados 29.8 vs 21.5%
Complicaciones postoperatorias 27.8 vs 22.8%
Edad ≥ 75 años tiene 2.5 veces más riesgo de fallecer en el postoperatorio que los de < 75 años
M Sun , F Abdollah , J Schmitges, M Bianchi, Z Tian, S Shariat, K Zorn, D Pharand , H Widmer, M Graefen, F Montorsi, P Perrotte, P Karakiewicz. Cytoreductive nephrectomy in the elderly: a population-based cohort from the USA. BJUI 2011: 109 , 1807 – 1812.
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NEFRECTOMÍA CITOREDUCTIVAEDAD
M Sun , F Abdollah , J Schmitges, M Bianchi, Z Tian, S Shariat, K Zorn, D Pharand , H Widmer, M Graefen, F Montorsi, P Perrotte, P Karakiewicz. Cytoreductive nephrectomy in the elderly: a population-based cohort from the USA. BJUI 2011: 109 , 1807 – 1812.
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NEFRECTOMÍA CITOREDUCTIVATERAPIA BLANCO NEOADJUVANTE
C Wood, V Margulis. Neoadjuvant (Presurgical) Therapy for Renal Cell Carcinoma: A New Treatment Paradigm for Locally Advanced and Metastatic Disease. Cancer May 15, 2009: 2355-2360.
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NEFRECTOMÍA CITOREDUCTIVA
TERAPIA BLANCO NEOADJUVANTE
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NEFRECTOMÍA CITOREDUCTIVATERAPIA BLANCO NEOADJUVANTE
C Wood, V Margulis. Neoadjuvant (Presurgical) Therapy for Renal Cell Carcinoma: A New Treatment Paradigm for Locally Advanced and Metastatic Disease. Cancer May 15, 2009: 2355-2360.
Terapia blanco prequirúrgica vs nefrectomía citorreductivainicial
No diferencias en parámetros perioperatorios
Parece ser seguro
Identifica pacientes que responden a terapia sistémica previo a la cirugía, evitando cirugía mórbida con pronóstico pobre
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NEFRECTOMÍA CITOREDUCTIVA
TERAPIA BLANCO NEOADJUVANTE
C Wood, V Margulis. Neoadjuvant (Presurgical) Therapy for Renal Cell Carcinoma: A New Treatment Paradigm for Locally Advanced and Metastatic Disease. Cancer May 15, 2009: 2355-2360.
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NEFRECTOMÍA CITOREDUCTIVAMETASTASECTOMÍA
P Russo, M Snyder, A Vickers, V Kondagunta, R Motzer. Cytoreductive Nephrectomy and Nephrectomy/Complete Metastasectomy for Metastatic Renal Cancer. The Scientific World JOURNAL (2007) 7, 768–778
91 pacientes1989 – 2003Memorial Sloan Kettering Cancer Center
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NEFRECTOMÍA CITOREDUCTIVAMETASTASECTOMÍA
P Russo, M Snyder, A Vickers, V Kondagunta, R Motzer. Cytoreductive Nephrectomy and Nephrectomy/Complete Metastasectomy for Metastatic Renal Cancer. The Scientific World JOURNAL (2007) 7, 768–778
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NEFRECTOMÍA CITOREDUCTIVAMETASTASECTOMÍA
P Russo, M Snyder, A Vickers, V Kondagunta, R Motzer. Cytoreductive Nephrectomy and Nephrectomy/Complete Metastasectomy for Metastatic Renal Cancer. The Scientific World JOURNAL (2007) 7, 768–778
Sobrevida media de nefrectomía/metastasectomía 30 meses vs 12 meses con solo nefrectomía citoreductiva
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NEFRECTOMÍA CITOREDUCTIVATENDENCIAS
ERA DE CITOKINAS
ERA DE TERAPIA BLANCO
C. Tsao, A. C. Small, M. Kates et al. Cytoreductive nephrectomy for metastatic renal cell carcinomain the era of targeted therapy in the United States: a SEER analysis. World J Urol. Published online: 08 dec 2012.
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NEFRECTOMÍA CITOREDUCTIVAROL EN LA ERA DE TERAPIA BLANCO
Choueiri TK, Xie W, Kollmannsberger C, et al. The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. J Urol2011;185:60.Bellmunt J. Future developments in renal cell carcinoma. Ann Oncol 2009; 20(Suppl 1):i13.Biswas S, Kelly J, Eisen T. Cytoreductive nephrectomy in metastatic clear-cell renal cell carcinoma: perspectives in the tyrosine kinase inhibitor era. Oncologist 2009;14:52.
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NEFRECTOMÍA CITOREDUCTIVAESTUDIOS EN FASE III
Estudio CARMENA2013
Sobrevida global
Estudio EORTC2014
Sobrevida libre de progresión
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¡ GRACIAS !