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Efecto de la quimioterapia adyuvante en el carcinoma urotelial de vejiga localmente avanzado tratado con cistectomía
Effect of adjuvant chemotherapy in locally advanced urothelial carcinoma of the bladder treated with cystectomy
G. del Pozo Jiméneza,
Autor para correspondencia
gemadpj@hotmail.com

Autor para correspondencia.
, F. Herranz Amob, J.A. Arranz Arijab, E. Rodríguez Fernándezb, D. Subirá Ríosb, E. Lledó Garcíab, G. Bueno Chomónb, M.J. Cancho Gilb, J. Carballido Rodrígueza, C. Hernández Fernándezb
a Servicio de Urología, Hospital Universitario Puerta de Hierro, Madrid, España
b Servicio de Urología, Hospital Universitario Gregorio Marañón, Madrid, España
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          "es" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Supervivencia c&#225;ncer espec&#237;fica por estadios&#46; pT3pN0 A&#41;&#44; pT4pN0<span class="elsevierStyleHsp" style=""></span>B&#41; y pT3-4pN&#43; C&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">El tumor vesical &#40;TV&#41; es la und&#233;cima neoplasia maligna m&#225;s com&#250;n en el mundo&#44; con 165&#46;084 muertes en 2012 en todo el mundo &#40;datos GLOBOCAN&#41;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#44;2</span></a>&#46; En Espa&#241;a&#44; aproximadamente el 90&#37; de todos los TV se caracterizan como carcinoma urotelial<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">El 30&#37; de los pacientes presentan un tumor m&#250;sculo-invasivo &#40;TVMI&#41; al diagn&#243;stico &#40;T2-4&#41;&#46; Adem&#225;s&#44; un 50-70&#37; de los TV no m&#250;sculo-invasivo &#40;TVNMI&#41; recurren y aproximadamente un 10-20&#37; de los mismos progresan a enfermedad infiltrante<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a>&#46; Llegados a este punto&#44; la cistectom&#237;a radical &#40;CR&#41; con linfadenectom&#237;a p&#233;lvica bilateral &#40;LNPB&#41; sigue siendo el tratamiento de elecci&#243;n en pacientes con TVMI<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A pesar de las mejoras t&#233;cnicas&#44; cuidados postoperatorios y terapias complementarias perioperatorias&#44; se objetiva solo una modesta mejor&#237;a en la supervivencia&#44; report&#225;ndose tasas de supervivencia c&#225;ncer espec&#237;fica &#40;SCE&#41; a los 5 a&#241;os de 50-66&#37;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;7</span></a>&#44; describi&#233;ndose como principales factores pron&#243;sticos de SCE tras CR el estadio patol&#243;gico local &#40;pT&#41; y la afectaci&#243;n ganglionar &#40;pN&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Aunque los datos para la quimioterapia adyuvante &#40;QTAdy&#41; son menos s&#243;lidos que para la quimioterapia neoadyuvante&#44; para la cual existe evidencia de nivel 1&#44; las pautas actuales ofrecidas por la Asociaci&#243;n Europea de Urolog&#237;a y la Sociedad Americana de Oncolog&#237;a Cl&#237;nica apoyan el uso de QTAdy basada en cisplatino despu&#233;s de la CR para pT3&#47;pT4 y&#47;o pN&#43;&#44; con la esperanza de disminuir el riesgo de recurrencia<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7&#8211;10</span></a>&#46; Sin embargo&#44; el papel de la QTAdy en TVMI permanece controvertido actualmente&#46;</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Objetivo</span><p id="par0025" class="elsevierStylePara elsevierViewall">Evaluar el efecto de la QTAdy en la SCE del TVMI localmente avanzado tras CR&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Material y m&#233;todo</span><p id="par0030" class="elsevierStylePara elsevierViewall">De la base de datos de cistectom&#237;as de nuestro servicio se han extra&#237;do los pacientes con TV urotelial puro tratados con CR entre 1986 y 2009 con un estadio pT3-4pN0&#47;&#43;cM0&#46; En total 292 pacientes&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">La cistectom&#237;a abierta fue la t&#233;cnica est&#225;ndar hasta el a&#241;o 2006 que se introdujo la t&#233;cnica laparosc&#243;pica &#40;CRL&#41;&#46; Se realiz&#243; LNPB est&#225;ndar en todos los pacientes&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">El riesgo anest&#233;sico se defini&#243; seg&#250;n el sistema de clasificaci&#243;n de la American Society of Anesthesiologist&#46; Las complicaciones posquir&#250;rgicas se agruparon seg&#250;n la clasificaci&#243;n de Clavien-Dindo<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a>&#46; Se recogieron las complicaciones acaecidas en los 60 d&#237;as posteriores a la cirug&#237;a&#46; Los pacientes fueron reclasificados seg&#250;n la clasificaci&#243;n TNM de la UICC &#40;7&#46;<span class="elsevierStyleHsp" style=""></span>&#170; edici&#243;n&#41; del a&#241;o 2009<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Se recomend&#243; QTAdy basada en el platino &#40;3 ciclos&#41; a todos los pacientes&#44; despu&#233;s de explicar los posibles beneficios y las complicaciones&#46; Cuando no fueron candidatos &#40;mal estado general&#44; mala funci&#243;n renal&#44; etc&#46;&#41; o rechazaron la QTAdy se les ofreci&#243; seguimiento&#46; Hasta el a&#241;o 1999 se utiliz&#243; metrotrexate&#44; vinblastina&#44; adriamicina&#44; cisplatino&#44; a partir del a&#241;o 2000 se introdujo la combinaci&#243;n de cisplatino &#43; gemcitabina&#46; En los pacientes con insuficiencia renal o contraindicaci&#243;n al cisplatino se utiliz&#243; carboplatino&#46; Ninguno de los pacientes recibi&#243; quimioterapia neoadyuvante&#46; El seguimiento se realiz&#243; al mes del alta&#44; a los 3 meses y cada 6 meses hasta el 5&#46;&#176; a&#241;o&#44; posteriormente un seguimiento anual&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Se trata de un estudio de cohortes retrospectivo&#44; con dos cohortes&#44; una tratada con QTAdy compuesta por 185&#40;63&#44;4&#37;&#41; pacientes y otra exclusivamente con seguimiento con 107&#40;36&#44;6&#37;&#41;&#46; Ambas fueron seguidas de forma prospectiva hasta la muerte o fecha de &#250;ltimo control&#46; Los datos de estas dos cohortes han sido recogidos de forma retrospectiva&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Las variables cuantitativas se han representado por la mediana y el rango intercuartil &#40;IQR&#41; y las cualitativas mediante frecuencias absolutas y porcentajes&#46; Para el contraste de variables cualitativas se utiliz&#243; el test de la Chi cuadrado y t de Student y ANOVA para las cuantitativas&#46; La estimaci&#243;n de la supervivencia se realiz&#243; con el m&#233;todo de Kaplan-Meier y el test de long-rank se emple&#243; para comparar las curvas de supervivencia&#46; Se realiz&#243; an&#225;lisis uni- y multivariante mediante regresi&#243;n de Cox para identificar primero las variables predictoras y posteriormente las variables predictoras independientes de mortalidad c&#225;ncer espec&#237;fica &#40;MCE&#41;&#46; Las variables significativas &#40;p&#60;0&#44;05&#41; y las que presentaron una tendencia a la significaci&#243;n &#40;p&#8804;0&#44;1&#41; se incluyeron en el an&#225;lisis multivariante&#46; Todos los c&#225;lculos se realizaron con el paquete estad&#237;stico IBM&#174; SPSS&#174; statistics v-21&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Resultados</span><p id="par0060" class="elsevierStylePara elsevierViewall">El 90&#44;1&#37; &#40;263&#41; fueron varones con una mediana de edad de 68 a&#241;os &#40;IQR 61-75&#41;&#59; 268 pacientes &#40;91&#44;8&#37;&#41; tuvieron un TVMI en la resecci&#243;n transuretral &#40;RTU&#41;&#46; En 33&#40;11&#44;3&#37;&#41; se observaron ganglios patol&#243;gicos en TAC de estadificaci&#243;n y en 118&#40;40&#44;4&#37;&#41; hidronefrosis&#46; El resto de las variables cl&#237;nicas de la serie y la comparaci&#243;n de las mismas entre ambas cohortes se describe en la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">En 249&#40;85&#44;3&#37;&#41; casos se realiz&#243; una derivaci&#243;n urinaria transintestinal&#44; siendo la m&#225;s frecuente la ileostom&#237;a cut&#225;nea transintestinal tipo Bricker &#40;214 &#91;86&#37;&#93; pacientes&#41;&#46; En 125 &#40;42&#44;8&#37;&#41; pacientes se observ&#243; invasi&#243;n ganglionar &#40;pN&#43;&#41; por la neoplasia&#46; El 52&#44;1&#37; &#40;152 casos&#41; de los pacientes present&#243; al menos una complicaci&#243;n postoperatoria de cualquier grado&#44; el 20&#44;5&#37; &#40;60 casos&#41; se clasific&#243; como Clavien-Dindo &#8805; III&#46; El resto de las variables quir&#250;rgicas y patol&#243;gicas de la serie y la comparaci&#243;n de las mismas entre ambas cohortes se describe en la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Los pacientes con complicaciones graves &#40;clavien-Dindo &#8805; III&#41; iniciaron la QTAdy m&#225;s tard&#237;amente &#40;6&#44;8 frente a 8&#44;6 semanas&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Tambi&#233;n tuvieron una mayor necesidad de reducci&#243;n de dosis o ciclos de tratamiento &#40;45&#44;5&#37; vs&#46; 67&#44;9&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;005&#41;&#46; Por este motivo la presencia de complicaciones graves se incluy&#243; en el an&#225;lisis multivariante&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Al final del estudio con una mediana de seguimiento de 40&#44;5 meses &#40;IQR 55-80&#44;5&#41;&#44; 67 pacientes &#40;22&#44;9&#37;&#41; se encontraban libres de tumor y 160&#40;54&#44;8&#37;&#41; hab&#237;an fallecido debido al TV&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a> se detalla la situaci&#243;n de los pacientes al final del estudio&#46; No se observaron diferencias significativas &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;36&#41; en la mediana de seguimiento de ambas cohortes &#40;QTAdy<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20 meses &#91;IQR 11-57&#93; y seguimiento<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#91;IQR 8-35&#93;&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">La mediana estimada de SCE de la serie completa fue de 30 meses &#40;IC95&#37; 20&#44;7-39&#44;2&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>A&#41;&#46; La mediana de SCE en los pacientes tratados con QTAdy fue de 34 meses &#40;IC95&#37;&#58;20&#44;3-47&#44;7&#41;&#44; frente a 27 meses &#40;IC95&#37; 18&#44;2-35&#44;8&#41; en los no tratados &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;38&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>B&#41;&#46; No se observaron diferencias significativas en la estimaci&#243;n de la SCE en funci&#243;n del tratamiento con QTAdy en los pacientes pT3pN0 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;25&#41; ni pT4pN0 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;29&#41;&#44; pero s&#237; en los pacientes pT3-4pN&#43; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>A&#44; B y C&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Se realiz&#243; una an&#225;lisis multivariante &#40;regresi&#243;n de Cox&#41;&#44; donde se incluyeron las variables con diferencias significativas entre ambas cohortes y que seg&#250;n la literatura pudieran influir en la MCE&#58; edad&#44; tipo de acceso quir&#250;rgico a la cistectom&#237;a&#44; estadio pTpN&#44; complicaciones graves &#40;Clavien-Dindo &#8805; III&#41; y tratamiento con QTAdy &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46; El estadio patol&#243;gico &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41; y el tratamiento con QTAdy &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41; se comportaron como factores pron&#243;sticos independientes relacionados con la MCE&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Se observ&#243; un incremento en la tasa instant&#225;nea de riesgo de muerte en pacientes con estadio pT4pN0 y pT3-4pN&#43; respecto a pacientes con pT3pN0 &#40;HR&#58;2&#44;17&#44; IC95&#37; 1&#44;36-3&#44;45&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#59; y HR&#58;3&#44;36&#44; IC95&#37; 2&#44;20-5&#44;14&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#44; respectivamente&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">La administraci&#243;n de QTAdy tuvo un efecto protector y redujo el riesgo de muerte c&#225;ncer espec&#237;fica de forma significativa respecto a los pacientes que no la recibieron &#40;HR&#58; 0&#44;59&#59; IC95&#37; 0&#44;40-0&#44;87&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discusi&#243;n</span><p id="par0100" class="elsevierStylePara elsevierViewall">En el trabajo que presentamos observamos que la administraci&#243;n de QTAdy redujo el riesgo de MCE por TV respecto a los pacientes que no la recibieron &#40;HR&#58; 0&#44;59&#44; IC95&#37; 0&#44;40-0&#44;87&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46; Sin embargo&#44; el papel de la QTAdy todav&#237;a est&#225; en debate&#46; Desde 1988&#44; se han publicado diferentes estudios con bajo n&#250;mero de pacientes y gran heterogeneidad en los resultados publicados<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13&#8211;16</span></a>&#46; En 1991&#44; Skinner et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a>&#46; public&#243; el primer estudio prospectivo que mostr&#243; beneficios potenciales de la QTAdy basada en cisplatino tras CR en pacientes con TVMI de alto riesgo&#46; Por el contrario&#44; los resultados de m&#250;ltiples ensayos prospectivos sugieren que no hay diferencias significativas&#46; Estos resultados pueden atribuirse a la exclusi&#243;n de pacientes con pN&#43; o la monoterapia con cisplatino en pacientes pT2pN0<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#8211;19</span></a>&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Debido a esta discordancia&#44; desde 2001&#44; tres ensayos aleatorizados en fase III han comparado la QTAdy con observaci&#243;n despu&#233;s de CR en casos de TVMI<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">20&#8211;22</span></a>&#46; Un estudio italiano incluy&#243; 194 pacientes con pT2G3 o pT3&#47;T4 y examin&#243; el efecto de GC sin encontrar diferencias estad&#237;sticamente significativas para SG &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;24&#41; y supervivencia libre de recurrencia &#40;SLR&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;70&#41;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a>&#46; El segundo ensayo&#44; realizado por SOGUG &#40;Grupo Espan&#771;ol Oncolog&#237;a Genitourinaria&#41;&#44; evalu&#243; a 142 sujetos tratados con CG&#43;P&#40;paclitaxel&#41; y mostr&#243; una diferencia en la SG a 5 a&#241;os que favoreci&#243; al brazo de QTAdy &#40;60&#37; vs&#46; 31&#37;&#59; p&#60;0&#44;001&#41; con una mediana de seguimiento de 30 meses<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a>&#46; Finalmente&#44; en 2015 se public&#243; el estudio prospectivo aleatorizado de la Organizaci&#243;n Europea para Investigaci&#243;n y Tratamiento del C&#225;ncer &#40;EORTC 30994&#41;&#44; que compar&#243; la QTAdy inmediata &#40;4 ciclos de GC&#44; M-VAC o HD M-VAC&#41; tras CR vs&#46; la QT diferida &#40;6 ciclos&#41; tras la reca&#237;da&#44; tras incluir 284 pacientes de los 660 previstos inicialmente&#46; A pesar de que no alcanz&#243; el objetivo primario &#40;SG&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;13&#41;&#44; la SLR fue mayor con la QTAdy inmediata frente a la diferida &#40;HR 0&#44;54&#59; IC95&#37;&#58; 0&#44;4-0&#44;73&#59; p &#60;0&#44;0001&#41;&#44; con una tasa de SLR a 5 an&#771;os del 47&#44;6 y 31&#44;8&#37; con QTAdy inmediata y diferida&#44; respectivamente<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Todos estos ensayos aleatorizados presentaron problemas en la metodolog&#237;a estad&#237;stica&#44; ya que la inclusi&#243;n de pacientes se cerr&#243; precozmente sin alcanzar el tama&#241;o muestral calculado&#44; resultando en estudios con bajo n&#250;mero de pacientes&#44; sin poder llegar a objetivos de supervivencia&#44; con lo que dif&#237;cilmente se pueden extraer buenas conclusiones de los mismos<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">23&#44;24</span></a>&#46; Solo el estudio del SOGUG mostr&#243; una gran ventaja en la SG del grupo con QTAdy en comparaci&#243;n con la observaci&#243;n<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a>&#46; En el trabajo de la EORTC&#44; se observ&#243; una ligera ventaja en la SG para los pacientes pN0&#44; pero este an&#225;lisis de subgrupos se limita a un pequen&#771;o n&#250;mero de pacientes<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>&#46; Por otra parte&#44; en el ensayo italiano&#44; no se observaron diferencias respecto a la afectaci&#243;n ganglionar<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Aunque los an&#225;lisis retrospectivos como el de este trabajo&#44; a menudo est&#225;n sujetos a sesgos&#44; existen tres estudios no aleatorizados con gran n&#250;mero de pacientes que presentan importancia a la hora de asesorar sobre QTAdy<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a>&#46; El estudio con mayor n&#250;mero de pacientes informado por Galsky et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a>&#44; utiliz&#243; datos de la National Cancer Database &#40;NCDB&#41; de la American Cancer Society para evaluar el beneficio cl&#237;nico de la QTAdy en pacientes con pT3&#47;T4 y&#47;o pN&#43;&#46; Se identificaron un total de 5653 pacientes tratados entre 2003-2006&#46; Se objetiv&#243; mejor&#237;a en la SG para la QTAdy respecto a la CR &#40;HR 0&#44;70&#59; IC95&#37;&#58; 0&#44;64- 0&#44;76&#41;&#46; Estos hallazgos crearon pol&#233;mica&#44; pudiendo estar limitados sus resultados por un sesgo de selecci&#243;n&#44; con una disminuci&#243;n del riesgo de muerte por otras causas<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a>&#46; Para hacer frente a esta limitaci&#243;n&#44; Froehner et al&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a>&#44; realizaron un an&#225;lisis de riesgos competitivos utilizando datos de una sola instituci&#243;n con 798 pacientes con TVMI con CR entre 1993-2011&#46; Un modelo multivariante confirm&#243; una reducci&#243;n de riesgo de MG y MCE del 50&#37; y 29&#37;&#44; respectivamente&#44; sin diferencias en t&#233;rminos de mortalidad por otras causas&#46; Del mismo modo&#44; Vetterlein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a>&#46; analizaron los datos de la base de datos multic&#233;ntrica europea PROMETRICS y mostraron que la QTAdy redujo la MG y MCE en un 53&#37; y 49&#37; &#40;p&#60;0&#44;05&#41;&#44; respectivamente&#46; Por otra parte&#44; en el estudio de Bostro&#776;m et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a>&#44; donde se incluyeron 581 pacientes&#44; se report&#243; que los pacientes con enfermedad &#8805;pT3y&#47;o N&#43; presentaban una mejor supervivencia si se les aplicaba QTAdy&#44; con una reducci&#243;n significativa del riesgo relativo del 40&#37; de muertes relacionadas con TVMI&#46; Estos resultados est&#225;n de acuerdo con los encontrados en nuestro trabajo &#40;HR&#58; 0&#44;59&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41; y con el trabajo multic&#233;ntrico de Svatek et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#44; donde se objetiv&#243; que la QTAdy mejor&#243; la supervivencia en los pacientes de m&#225;s alto riesgo &#40;&#8805;pT3 y pN&#43;&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">En nuestro estudio&#44; encontramos que los pacientes que no recibieron QTAdy presentaron una mediana de SCE de 27 meses respecto a los que s&#237; la recibieron de 34 meses&#44; sin objetivar diferencias estad&#237;sticamente significativas &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;38&#41;&#44; resultados similares a Cognetti<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> o Stenberget et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>&#46; No obstante&#44; estratificando los pacientes por estadios objetivamos un aumento de SCE &#250;nicamente en los pacientes con pN&#43; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; similar al estudio de Svatek et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#59; y a diferencia del estudio de la EORTC<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> y de Bo&#776;strom et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">As&#237; mismo&#44; en la tesis realizada por el Dr&#46; Arranz&#44; onc&#243;logo del Hospital Universitario Gregorio Mara&#241;&#243;n&#44; donde realiz&#243; un estudio de cohortes retrospectivo con una serie de pacientes muy similar a la utilizada en nuestro trabajo&#44; recogida desde 1987-2013&#44; observ&#243; que la administraci&#243;n de la QTady se asoci&#243; con una reducci&#243;n estad&#237;sticamente significativa del riesgo de reca&#237;da despu&#233;s de CR&#44; aunque el beneficio se encontr&#243; solo en pacientes con tumores con extensi&#243;n extravesical o afectaci&#243;n ganglionar &#40;HR&#58; 0&#44;56 y HR&#58; 0&#44;39&#44; respectivamente&#41;&#46; La QTAdy tambi&#233;n se asoci&#243; de forma estad&#237;sticamente significativa con una reducci&#243;n del riesgo de muerte relacionada con tumor &#40;HR 0&#44;57&#41;&#44; sin observar diferencias en el efecto observado en funci&#243;n del esquema de quimioterapia utilizado<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a>&#46; La diferencia entre los diferentes estudios referidos se puede objetivar en la <a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">Dos metaan&#225;lisis han confirmado un beneficio de supervivencia para pacientes que recibieron QTAdy en comparaci&#243;n con CR solamente<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8&#44;9</span></a>&#46; En el primero en 2005 analizaron 491 pacientes de seis ensayos&#44; aleatoriz&#225;ndose a recibir o no QTAdy tras CR&#44; report&#225;ndose un 25&#37; de reducci&#243;n del riesgo relativo de muerte &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41; y siendo los pacientes con las caracter&#237;sticas de mayor riesgo &#40;&#8805; pT3 y N&#43;&#41;&#44; los que experimentaron el beneficio de supervivencia m&#225;s significativo de la QTAdy &#40;HR&#58; 0&#44;75&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a>&#46; En 2014&#44; una revisi&#243;n sistem&#225;tica que inclu&#237;a un metaan&#225;lisis de nueve ensayos aleatorios &#40;sin incluir el estudio EORTC&#41; con un total de 945 pacientes&#44; demostr&#243; una ventaja en la SG y la SLR&#44; con una reducci&#243;n del riesgo de muerte y progresi&#243;n de la enfermedad del 23&#37; &#40;HR 0&#44;77&#44; IC95&#37;&#58; 0&#44;59-0&#44;99&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; y el 34&#37; &#40;HR 0&#44;66&#44; IC95&#37; 0&#44;45-0&#44;91&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#44; respectivamente&#44; siendo m&#225;s evidente la SLR para pacientes con afectaci&#243;n ganglionar<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a>&#46; Despu&#233;s de actualizar este metaan&#225;lisis para incluir el estudio EORTC&#44; los resultados sugieren un beneficio del tratamiento inmediato en la SG &#40;HR 0&#44;77&#59; IC95&#37;&#58;0&#44;65 a 0&#44;91&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Si tenemos en cuenta este trabajo&#44; se trata de una serie amplia con un buen estudio metodol&#243;gico que refleja nuestra pr&#225;ctica habitual y determina aquellas variables predictoras de SCE tras CR&#44; identificando que la aplicaci&#243;n de QTAdy puede ser &#250;til en la reducci&#243;n de la MCE&#46; No obstante&#44; es compleja su comparaci&#243;n con otros estudios publicados&#44; debido a la heterogeneidad en los resultados de los mismos&#44; as&#237; como en los reg&#237;menes de QT utilizados&#44; n&#250;mero de ciclos sub&#243;ptimos&#8230;&#59; no aclarando si la QTAdy favorece la SCE&#44; aunque parece que seg&#250;n los resultados de los &#250;ltimos metaan&#225;lisis se debe considerar en pacientes de alto riesgo con diseminaci&#243;n extravesical y ganglios patol&#243;gicos<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a>&#44; como refleja nuestro estudio&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Sin embargo&#44; este trabajo presenta ciertas limitaciones&#58; a&#41; serie hist&#243;rica retrospectiva con periodo largo de estudio&#59; b&#41; variabilidad entre diferentes tipos de r&#233;gimen de QTAdy a lo largo del periodo&#59; c&#41; no inclusi&#243;n de ciertas variables &#40;infiltraci&#243;n linfovascular&#44; n&#250;mero de ganglios en la LNPB&#44; o m&#225;rgenes quir&#250;rgicos&#41; que se comportan como factores pron&#243;sticos de supervivencia en otras publicaciones&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusiones</span><p id="par0145" class="elsevierStylePara elsevierViewall">En pacientes con TV urotelial localmente avanzado&#44; el estadio patol&#243;gico pTpN se comport&#243; como factor pron&#243;stico independiente de MCE despu&#233;s de la CR&#46; La administraci&#243;n de QTAdy en nuestra serie se comport&#243; como un factor protector reduciendo significativamente el riesgo de MCE&#44; aunque en el an&#225;lisis por estadios&#44; &#250;nicamente los pacientes pN&#43; se vieron beneficiados&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicto de intereses</span><p id="par0150" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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            0 => "Tumor vesical"
            1 => "Cistectom&#237;a"
            2 => "Factores pron&#243;sticos"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introducci&#243;n</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">El papel de la quimioterapia adyuvante &#40;QTAdy&#41; en el tumor vesical m&#250;sculo-invasivo sigue siendo controvertido actualmente&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Evaluar el efecto de la QTAdy en la supervivencia c&#225;ncer espec&#237;fica del tumor vesical m&#250;sculo-invasivo tras cistectom&#237;a radical &#40;CR&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Material y m&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">An&#225;lisis retrospectivo de 292 pacientes diagnosticados de tumor vesical urotelial tratados con CR entre 1986-2009 con estadio pT3-4pN0&#47;&#43;cM0&#44; divididas en dos cohortes&#58;185&#40;63&#44;4&#37;&#41; pacientes tratados con QTAdy y otra con 107&#40;36&#44;6&#37;&#41; sin QTAdy&#46; Mediana de seguimiento de 40&#44;5 meses &#40;IQR 55-80&#44;5&#41;&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">An&#225;lisis comparativo con test Chi cuadrado y t Student&#47;ANOVA&#46; C&#225;lculo de supervivencia con el m&#233;todo de Kaplan-Meier y test de long-rank&#46; An&#225;lisis multivariante &#40;regresi&#243;n de Cox&#41; para identificar variables predictoras independientes de mortalidad c&#225;ncer espec&#237;fica &#40;MCE&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El 42&#44;8&#37; de la serie present&#243; afectaci&#243;n ganglionar tras CR&#46; Al finalizar el seguimiento&#44; 22&#44;9&#37; estaban libres de tumor vesical y 54&#44;8&#37; hab&#237;an fallecido por esa causa&#46; La mediana de supervivencia c&#225;ncer espec&#237;fica fue de 30 meses&#46; No se observaron diferencias significativas en supervivencia c&#225;ncer espec&#237;fica en funci&#243;n del tratamiento con QTAdy en pacientes pT3pN0 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;25&#41; ni pT4pN0 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;29&#41;&#44; pero s&#237; en pT3-4pN&#43; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En el an&#225;lisis multivariante se identificaron el estadio patol&#243;gico &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41; y el tratamiento con QTAdy &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41; como factores pron&#243;sticos independientes de MCE&#46; La QTAdy redujo el riesgo de MCE &#40;HR&#58;0&#44;59&#44; IC95&#37; 0&#44;40-0&#44;87&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusiones</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El estadio pT y pN se identificaron como variables predictoras independientes de MCE tras CR&#46; La administraci&#243;n de QTAdy en nuestra serie se comport&#243; como factor protector reduciendo el riesgo de MCE&#44; aunque en el an&#225;lisis por estadios&#44; &#250;nicamente los pacientes pN&#43; se vieron beneficiados&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introduction</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Currently&#44; the role of adjuvant chemotherapy &#40;ADJ&#41; in muscle invasive bladder tumor remains controversial&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objective</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">To evaluate the effect of ADJ on cancer specific survival of muscle invasive bladder tumor after radical cystectomy &#40;RC&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material and methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Retrospective analysis of 292 patients diagnosed with urothelial bladder tumor pT3-4pN0 &#47; &#43; cM0 stage&#44; treated with RC between 1986-2009&#46; Total cohort was divided in two groups&#58; 185 &#40;63&#46;4&#37;&#41; patients treated with ADJ and 107 &#40;36&#46;6&#37;&#41; without ADJ&#46; Median follow-up was 40&#46;5 months &#40;IQR 55-80&#46;5&#41;&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparative analysis was performed with Chi-square test and Student&#39;s t test &#47;ANOVA&#46; Survival analysis was carried out with the Kaplan-Meier method and log-rank test&#46; Multivariate analysis &#40;Cox regression&#41; was made to identify independent predictors of cancer-specific mortality &#40;CSM&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Results</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">42&#46;8&#37; of the series presented lymph node involvement after RC&#46; At the end of follow-up&#44; 22&#46;9&#37; were BC-free and 54&#46;8&#37; had died due to this cause&#46; The median cancer specific survival was 30 months&#46; No significant differences were observed in cancer specific survival regarding the treatment with ADJ in pT3pN0 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;25&#41; or pT4pN0 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;29&#41; patients&#44; but it was significant in pT3-4pN&#43; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Multivariate analysis showed pathological stage &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41; and treatment with ADJ &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;007&#41; as independent prognostic factors for CSM&#46; ADJ reduced the risk of CSM &#40;HR&#58;0&#46;59&#44;95&#37; CI 0&#46;40-0&#46;87&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;007&#41;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusions</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">pT and pN stages were identified as independent predictors of CSM after RC&#46; The administration of ADJ in our series behaved as a protective factor reducing the risk of CSM&#44; although only pN&#43; patients were benefited in the stage analysis&#46;</p></span>"
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          "es" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Situaci&#243;n de los pacientes al final del estudio</p>"
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          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Negrita&#58; p de las variables que en el an&#225;lisis multivariante han sido estad&#237;sticamente significativas&#46;</p>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IC95&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">P&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#44;98-1&#44;02&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="3" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Acceso quir&#250;rgico</span></td><td class="td" title="\n
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                  \t\t\t\t">0&#44;13</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Abierto&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ref&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Laparosc&#243;pico&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;47-1&#44;10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;0001</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>pT3pN0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ref&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>pT4pN0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#44;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;36-3&#44;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>pT3-4pN&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;20-5&#44;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Complicaciones Clavien &#8805; III</span></td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ref&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;73-1&#44;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">QTAdy</span>&#46;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;007</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ref&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>S&#237;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;40-0&#44;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Estudio &#40;a&#241;o de publicaci&#243;n&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pacientes randomizados &#40;N&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Elecci&#243;n de estadio &#40;TNM&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">A&#241;os de reclutamiento&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Quimioterapia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SLR &#40;observaci&#243;n vs&#46; QTAdy&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SG &#40;observaci&#243;n vs&#46; QTAdy&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Skinner et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> &#40;1991&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">102&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pT3-pT4 o N&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;1980-1988&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Combinaciones de cisplatino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLR a 3 a&#241;os de 46&#37; vs &#46;70&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mediana de SG de 2&#44;4 vs&#46; 4&#44;3 a&#241;os&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paz-Ares et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> &#40;2010&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">142&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pT3-pT4 y&#47;o pN&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;2000-2007&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PGC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLR a 3 a&#241;os de 44&#37; vs&#46; 73&#37;&#59; p&#60;0&#44;0001&#44; HR 0&#44;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mediana SG 26 meses vs&#46; no alcanzadaSG a 5 a&#241;os 31&#37; vs &#46;60&#37;&#59; p&#60;0&#44;0009&#44; HR 0&#44;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cognetti et al&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> &#40;2012&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">194&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pT2G3&#44; N0-2&#59; pT3-4&#44; N0-2&#59; o pN1-2&#44; cualquier T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;2001-2007&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLR 42&#44;3&#37; vs&#46; 37&#44;2&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;70&#44; HR 1&#44;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SG a 5 a&#241;os 48&#44;5&#37; &#40;ambos brazos&#41;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;24&#44; HR 1&#44;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stenberg et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> &#40;2015&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">284&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pT3-4 y&#47;o pN&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;2002-2008&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GC&#44;MVAC o DD-MVAC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLR 31&#44;8&#37; vs&#46; 47&#44;6&#37;&#59; p&#60;0&#44;0001&#44; HR 0&#44;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mediana de SG 6&#44;7 vs&#46; 4&#44;6 a&#241;osSG a 5 a&#241;os 53&#44;6&#37; vs&#46; 47&#44;7&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;13&#44; HR 0&#44;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Galsky et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> &#40;2016&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5653&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pT3-4 y&#47;o N&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;2003-2006&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Combinaciones de cisplatino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SG a 5 a&#241;os 29&#44;1&#37; vs &#46;37&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#44; HR 0&#44;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Arranz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> &#40;2015&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">590&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pT2-T4 y &#47;o N&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;1987-2013&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MVAC O GC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLR a 5 a&#241;os 39&#44;1&#37; vs &#46;49&#44;6&#37;&#59; p&#60; 0&#44;04&#59; HR 1&#44;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SG a 5 a&#241;os 41&#44;2&#37; vs&#46; 46&#44;6&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;78&#59; HR 1&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Froehner et al&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> &#40;2016&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">798&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pT1G3 y&#47;o pT2-4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;1993-2011&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Combinaciones de cisplatino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Riesgo MG 50&#37;&#46; HR 0&#44;50&#44; p&#60;0&#44;0001&#46;Riesgo MCE 29&#37;&#59; HR 0&#44;71&#44; p&#61;0&#44;0321&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vetterlein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> &#40;2016&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">224&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pT3-4 y&#47;o N&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2011&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Combinaciones de cisplatino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SG a 3 a&#241;os 40&#44;9&#37; vs&#46; 62&#44;1&#37;&#59; p&#61;0&#44;014&#59; HR 0&#44;47SCE a 3 a&#241;os 51&#44;3&#37; vs 67&#44;1&#37;&#44; p&#61;0&#44;044&#59; HR 0&#44;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2252498.png"
              ]
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        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Resumen de los principales ensayos cl&#237;nicos sobre QTAdy en TVMI tras CR</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Bibliograf&#237;a"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:30 [
            0 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "World Health Organization&#46; GLOBOCAN 2012&#58; estimated cancer incidence&#44; mortality and prevalence worldwide in 2012&#46; &#91;consultado 15 Nov 2018&#93;&#46; Disponible en&#58; http&#58;&#47;&#47;globocan&#46;iarc&#46;fr&#47;Default&#46;aspx&#46;"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "International variations in bladder cancer incidence and mortality"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Chavan"
                            1 => "F&#46; Bray"
                            2 => "J&#46; Lortet-Tieulent"
                            3 => "M&#46; Goodman"
                            4 => "A&#46; Jemal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.eururo.2013.10.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Urol&#46;"
                        "fecha" => "2014"
                        "volumen" => "66"
                        "paginaInicial" => "59"
                        "paginaFinal" => "73"
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Información del artículo
ISSN: 02104806
Idioma original: Español
DOI:10.1016/j.acuro.2019.08.009
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