PCA3 como biomarcador de segunda línea en un programa de screening oportunista prospectivo, aleatorizado y controlado

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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">&#193;reas bajo la curva obtenidas para el PCA3&#44; la calculadora de riesgo 3 del ERSPC y la del modelo obtenido en nuestra serie PSE&#44; PCA3 y tacto rectar&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">Los resultados de cribado aleatorizado europeo en c&#225;ncer de pr&#243;stata &#40;ERSPC&#41; a los 13 a&#241;os de seguimiento han demostrado&#44; despu&#233;s del ajuste por no participaci&#243;n&#44; que la tasa de mortalidad por c&#225;ncer de pr&#243;stata &#40;CaP&#41; en hombres que fueron examinados fue de 0&#44;73 &#40;IC 95&#37;&#58; 0&#44;61-0&#44;88&#41;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a>&#46; Dado que la prueba del ant&#237;geno prost&#225;tico espec&#237;fico &#40;PSA&#41; es a menudo solicitada por los hombres y los m&#233;dicos generalistas est&#225;n empujados a realizarla&#44; la detecci&#243;n oportunista es una realidad&#46; De ah&#237; la necesidad de optimizar el cribado para evitar biopsias innecesarias &#40;Bx&#41; y su morbilidad asociada inherente<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">2&#44;3</span></a>&#44; as&#237; como la confrontaci&#243;n con el diagn&#243;stico de c&#225;ncer<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">4&#44;5</span></a>&#46; Adem&#225;s&#44; el cribado oportunista ha dado lugar a m&#225;s sobrediagn&#243;stico&#44; con casi el doble del n&#250;mero de hombres necesarios para ser diagnosticados para salvar a un hombre de morir de CaP en comparaci&#243;n con los hombres a los que se ofreci&#243; un programa de cribado bienal organizado<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">6</span></a>&#44; por lo que parece necesario optimizar su uso hasta que el cribado de CaP basado en la poblaci&#243;n no sea aprobado por los reguladores de salud&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">PSA3 se incorpor&#243; en los procedimientos de diagn&#243;stico de rutina en CaP en nuestra pr&#225;ctica diaria en 2009&#44; tanto para Bx inicial &#40;BxI&#41; como para biopsias de seguimiento &#40;BxS&#41;&#46; En nuestra experiencia&#44; los mejores resultados obtenidos de una puntuaci&#243;n de PCA3 fueron en el escenario BxI<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">7</span></a>&#46; Otros autores han demostrado su valor cuando se utiliza como una variable continua en un escenario de cribado oportunista<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">8</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Hemos dise&#241;ado un estudio prospectivo aleatorizado para evaluar PCA3 como un biomarcador de segunda l&#237;nea&#44; despu&#233;s del PSA y el tacto rectal &#40;TR&#41; y ha sido publicado previamente<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">9</span></a>&#46; Se evalu&#243; el rendimiento de PCA3 y su capacidad para reducir falsos negativos en BxI&#46; El rendimiento de PCA3 como &#250;nico biomarcador de segunda l&#237;nea se compara con el modelo de calculadora de riesgo 3 &#40;ERSPC RC-3&#41; &#40;<a id="intr0005" class="elsevierStyleInterRef" href="http://www.prostatecancer-riskcalculator.com/">http&#58;&#47;&#47;www&#46;prostatecancer-riskcalculator&#46;com</a>&#41;&#44; que predice la posibilidad de una biopsia por sextantes positiva en un hombre que nunca ha sido evaluado y tambi&#233;n eval&#250;a el grado de agresividad sin la necesidad de una ETR usando solo PSA total&#44; TR y una Bx por sextantes en una poblaci&#243;n mayor &#40;55-74&#41;&#44; ya que este es el m&#225;s comparable entre modelos de calculadoras de riesgo ERSPC en nuestro protocolo&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">M&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">Se trata de un estudio prospectivo y aleatorizado realizado entre septiembre de 2010 y julio de 2015 con los siguientes criterios de inclusi&#243;n&#58; varones sanos de 40-75 a&#241;os de edad&#44; con m&#225;s de 10 a&#241;os de expectativa de vida que solicitaron y fueron informados para la detecci&#243;n oportunista de CaP en el sistema p&#250;blico de salud&#46; Se requiri&#243; consentimiento informado por escrito antes de la inscripci&#243;n&#46; Se excluyeron los hombres con Bx de pr&#243;stata previa o antecedentes de infecciones del tracto urinario en el &#250;ltimo a&#241;o&#46; El estudio fue aprobado por el Comit&#233; de &#201;tica Institucional &#40;n&#250;m&#46; ref&#46; 2010-20&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Los pacientes con TR normal realizado por un ur&#243;logo y PSA &#60;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml se siguen con TR y PSA adicionales a los 4&#44; 3&#44; 2 o 1 a&#241;os si el PSA es &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;5&#44; 0&#44;5-1&#44; 1-2 o 2-3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; respectivamente&#46; Los pacientes con PSA &#8805;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;no se contempla l&#237;mite superior&#41; o PSA &#8805;<span class="elsevierStyleHsp" style=""></span>1&#44;5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml bajo tratamiento con finasterida&#47;dutasterida y TR normal se someten a un segundo TR por un ur&#243;logo diferente y se recoge una muestra de orina para determinar el PCA3 &#40;Progensa&#8482; Gene Probe-Hologic&#44; San Diego&#44; EE&#46;<span class="elsevierStyleHsp" style=""></span>UU&#46;&#41;&#46; Para este estudio&#44; 46 hombres con TR anormal detectados por los 2 ur&#243;logos fueron excluidos de este an&#225;lisis y fueron directamente biopsiados debido al alto riesgo de albergar CaP<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">10&#44;11</span></a>&#46; Por lo tanto&#44; los hombres con PSA &#8805;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml y TR normal sometidos a pruebas de PCA3 comprenden el grupo de estudio&#46; Todas las muestras de PCA3 se consideraron evaluables&#46; A los hombres con PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35 se les realiza una BxI est&#225;ndar de 12 cilindros&#46; Aquellos con PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35 son ciegamente asignados al azar por un programa inform&#225;tico 1&#58; 1&#44; ya sea a BxI o a observaci&#243;n &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Los hombres con CaP detectados en BxI o BxS tuvieron que retirarse del programa de detecci&#243;n&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">A los pacientes con BxI negativa se les pidi&#243; que acudieran a una consulta de seguimiento a los 6 meses y luego anualmente&#44; realizando PSA y TR en cada visita&#46; Durante el seguimiento&#44; se recomendar&#225; BxI o BxS &#40;16-18 cilindros&#41; a hombres con los siguientes criterios&#58; aumento de PSA&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml en la visita a los 6 meses o &#62;<span class="elsevierStyleHsp" style=""></span>0&#44;75<span class="elsevierStyleHsp" style=""></span>ng&#47;ml a un a&#241;o de los valores anteriores&#44; o TR anormal&#46; Si una segunda Bx es negativa para CaP&#44; el protocolo se abre y el seguimiento&#44; la indicaci&#243;n de Bx de repetici&#243;n&#44; RMmp u otros biomarcadores se basan en las recomendaciones del ur&#243;logo y la disposici&#243;n del paciente&#46; Definimos CaP cl&#237;nicamente significativo al que no entra en nuestro programa de vigilancia activa<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">12</span></a>&#44; por lo tanto&#44; CaP Gleason<span class="elsevierStyleSup">&#174;</span>7 y&#47;o cualquier CaP excepto m&#225;s de 2 cilindros afectados&#46; Todas las Bx son analizadas por el mismo uropat&#243;logo &#40;A&#46;C&#46;&#41;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Se realizaron comparaciones de frecuencias utilizando la prueba &#967;<span class="elsevierStyleSup">2</span> &#40;con la prueba exacta de Fisher para las tablas de contingencia 2<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>2&#41; para las variables categ&#243;ricas&#46; Para las variables continuas&#44; las diferencias entre las medias se compararon mediante la prueba t de Student&#46; Cuando la normalidad no fue aceptada&#44; las muestras se compararon utilizando la prueba U de Mann-Whitney&#46; Para evitar el sesgo de verificaci&#243;n debido a la aleatorizaci&#243;n en un brazo&#44; se utiliz&#243; el m&#233;todo de ponderaci&#243;n de probabilidad inversa &#40;PPI&#41; para obtener la sensibilidad&#44; especificidad y &#225;rea bajo la curva &#40;ABC&#41; corregidas de las caracter&#237;sticas operatorias del receptor &#40;COR&#41;&#46; Los modelos de regresi&#243;n log&#237;stica univariable para predecir la presencia de CaP en BxI se ajustaron para diferentes factores pron&#243;sticos&#46; Se ajust&#243; un modelo de regresi&#243;n log&#237;stica multivariante utilizando los factores univariados significativos para un nivel de significaci&#243;n del 10&#37;&#46; Para este modelo multivariante obtuvimos su nomograma asociado&#46; Exploramos los efectos cl&#237;nicos de diferentes modelos que realizan sus curvas de decisi&#243;n&#46; En el an&#225;lisis de seguimiento&#44; la mediana de tiempo libre de biopsia se estim&#243; utilizando el enfoque de Kaplan-Meier&#46; Se utilizaron pruebas de 2 caras y un valor de p<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#44;05 se consider&#243; estad&#237;sticamente significativo&#46; Los datos se analizaron usando R<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a>&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Resultados</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Poblaci&#243;n</span><p id="par0040" class="elsevierStylePara elsevierViewall">Un total de 5&#46;694 hombres solicitaron un programa de detecci&#243;n oportunista &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Las caracter&#237;sticas de los pacientes y las razones de las exclusiones se muestran en las <a class="elsevierStyleCrossRef" href="#sec0065">tablas <span class="elsevierStyleSmallCaps">I</span> y <span class="elsevierStyleSmallCaps">II</span> del material suplementario</a>&#46; Al final&#44; 5&#46;199 hombres fueron incluidos en este programa&#44; con una mediana de seguimiento de 29 meses&#46; La mediana de edad fue de 57 a&#241;os&#44; con un PSA medio de 1&#44;53<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;DE<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;49&#41;&#46; Ochocientos treinta y ocho hombres &#40;16&#44;1&#37;&#41; se sometieron a pruebas de PCA3&#59; 646 &#40;77&#44;1&#37;&#41; se inscribieron en la primera ronda&#44; y luego 125&#44; 48 y 19 en la segunda&#44; tercera y cuarta rondas&#44; respectivamente&#46; Las caracter&#237;sticas de los pacientes tambi&#233;n se muestran en el material adicional&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">La mediana de la puntuaci&#243;n PCA3 fue 23 &#40;rango 1-371&#41;&#46; Se detect&#243; PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35 en 301 hombres &#40;35&#44;9&#37;&#41;&#44; mientras que 537 &#40;64&#44;1&#37;&#41; presentaron PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&#46; Los hombres con PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35 eran mayores &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y no se encontraron diferencias en el tama&#241;o de la pr&#243;stata estimado por TR &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; El ERSPC RC-3 mostr&#243; un riesgo medio de 15&#44;6&#37; para una BxI por sextantes positiva en nuestro grupo de estudio&#46; PSA y PCA3 no se correlacionaron y mostraron un coeficiente de correlaci&#243;n d&#233;bil &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;028&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;413&#41; &#40;<a class="elsevierStyleCrossRef" href="#sec0065">figura <span class="elsevierStyleSmallCaps">I</span> del material suplementario</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Detecci&#243;n de c&#225;ncer de pr&#243;stata despu&#233;s de la biopsia inicial</span><p id="par0050" class="elsevierStylePara elsevierViewall">Todos los hombres con PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35&#44; as&#237; como 256 del grupo PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&#44; se sometieron a BxI&#46; Cabe se&#241;alar que 13 hombres con PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35 inicialmente asignados al azar al brazo de biopsia lo rechazaron y se incluyeron en el brazo de observaci&#243;n&#46; Las diferencias en las tasas de detecci&#243;n de CaP fueron estad&#237;sticamente significativas entre BxI realizada en los brazos PCA3&#40;&#43;&#41; &#40;38&#44;2&#37;&#41; y PCA3&#40;&#8211;&#41; &#40;18&#44;0&#37;&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; En la configuraci&#243;n de BxI&#44; 73 &#40;24&#44;3&#37;&#41; y 27 &#40;10&#44;5&#37;&#41; tuvieron CaP cl&#237;nicamente significativo detectado en los brazos PCA3&#40;&#43;&#41; y PCA3&#40;&#8211;&#41;&#44; respectivamente &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Para analizar el rendimiento de PCA3 con este protocolo&#44; debemos considerar el sesgo de verificaci&#243;n en nuestros datos&#46; Los casos de PCA3&#40;&#43;&#41; tienen m&#225;s probabilidades de ser diagnosticados de c&#225;ncer en BxI que los casos de PCA3&#40;&#8211;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Cuando se utiliz&#243; el m&#233;todo PPI para PCA3&#44; el corte establecido de 35 ten&#237;a una sensibilidad y especificidad corregidas del 54&#44;3&#37; &#40;IC 95&#37;&#58; 47&#44;3-61&#44;2&#41; y del 70&#44;3&#37; &#40;IC 95&#37;&#58; 66&#44;6-73&#44;9&#41;&#44; respectivamente&#46; Se muestran diferentes resultados con otro corte de PCA3 y figuras de ERSPC RC-3 en la <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#46; Se utiliz&#243; un valor de corte de 35 para PCA3 en 301 BxI con 97 falsos negativos&#46; Siguiendo las recomendaciones de ERSPC RC-3 para hacer BxI&#44; estimamos 196 BxI con 152 falsos negativos&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> muestra el an&#225;lisis de regresi&#243;n log&#237;stica univariante y multivariante para evaluar la probabilidad de una BxI positiva&#46; Se observ&#243; que PCA3 y las 2 variables contempladas por el ERSPC RC-3 son factores predictivos independientes&#46; Hemos construido un nomograma con estas 3 variables&#44; mostradas en datos complementarios &#40;<a class="elsevierStyleCrossRef" href="#sec0065">figura <span class="elsevierStyleSmallCaps">II</span> del material suplementario</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a> muestra las curvas ROC asociadas con la probabilidad de una BxI positiva de ERSPC RC-3 y PCA3&#46; Las ABC corregidas de PCA3 y ERSPC RC-3 fueron 0&#44;703 &#40;IC 95&#37;&#58; 0&#44;678-0&#44;728&#41; y 0&#44;580 &#40;IC 95&#37;&#58; 0&#44;547-0&#44;612&#41;&#44; respectivamente&#46; El ABC del modelo completo de 0&#44;719 &#40;IC 95&#37;&#58; 0&#44;695-0&#44;744&#41; es similar al ABC de PCA3 &#250;nico&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Beneficio neto</span><p id="par0070" class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#fig0015">figura 3</a> muestra las curvas de beneficios netos a trav&#233;s de diferentes probabilidades de umbral para cada uno de los 3 modelos&#46; Estas curvas se han calculado sobre la base de hombres biopsiados&#44; aunque despu&#233;s de la correcci&#243;n para el sesgo de verificaci&#243;n&#44; ninguno de los ABC obtenidos se ajustaron en m&#225;s de 0&#44;010&#46; Por lo tanto&#44; no esperamos que el sesgo de verificaci&#243;n tenga un efecto importante en el an&#225;lisis de la curva de decisi&#243;n&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Detecci&#243;n del c&#225;ncer de pr&#243;stata durante el seguimiento</span><p id="par0075" class="elsevierStylePara elsevierViewall">Teniendo en cuenta que 161 pacientes con detecci&#243;n de CaP en BxI fueron excluidos&#44; los 677 hombres restantes fueron seguidos durante una mediana de tiempo de 21&#44;7 meses &#40;rango 1-60&#41;&#46; Un total de 184 BxS se realizaron en 167 hombres &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Nuestra serie se estableci&#243; en 3 brazos&#58; PCA3&#40;&#43;&#41;&#59; PCA3&#40;&#8211;&#41;&#47;aleatorizado a BxI&#44; y PCA3&#40;&#8211;&#41;&#47;asignado al azar a observaci&#243;n&#46; El n&#250;mero de BxS realizadas fue de 37&#44; 34 y 113 en los 3 grupos&#44; encontrando 8 &#40;21&#44;6&#37;&#41;&#44; 5 &#40;14&#44;7&#37;&#41; y 28 &#40;24&#44;8&#37;&#41; casos de CaP&#44; respectivamente&#46; A los 12 y 24 meses&#44; el 84&#44;2&#37; &#40;IC 95&#37;&#58; 81&#44;1-87&#44;3&#37;&#41; y el 70&#44;1&#37; &#40;IC 95&#37;&#58; 65&#44;8-74&#44;4&#37;&#41; de los hombres se libraron de BxS&#44; respectivamente&#46; Para los 281 hombres PCA3&#40;&#8211;&#41; asignados al azar a observaci&#243;n&#44; la mediana de tiempo libre de BxI fue de 32&#44;2 meses &#40;IC 95&#37;&#58; 28&#44;9-35&#44;5&#41;&#46; A los 12 meses despu&#233;s de ingresar al protocolo&#44; el 75&#44;1&#37; &#40;IC 95&#37;&#58; 69&#44;4-80&#44;8&#37;&#41; de estos hombres se liberaron de BxI&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Entre las 184 BxS&#44; se detectaron 41 casos de CaP&#58; 8 en BxS entre hombres PCA3&#40;&#43;&#41; &#40;4&#44;3&#37;&#41;&#44; con un menor porcentaje de c&#225;ncer en los n&#250;cleos y solo 2 Gleason 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4 CaP&#59; y 33 entre hombres PCA3&#40;&#8211;&#41; &#40;6&#44;7&#37;&#41;&#44; 5 en la configuraci&#243;n de BxI&#44; y con una cantidad similar de cilindros afectados y porcentaje de tumor en los cilindros en comparaci&#243;n con el resto del CaP detectado&#46; Sin embargo&#44; entre estos 33 CaP&#44; 15 &#40;45&#44;5&#37;&#41; fueron Gleason &#8805;<span class="elsevierStyleHsp" style=""></span>7&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Detecci&#243;n global de c&#225;ncer de pr&#243;stata</span><p id="par0085" class="elsevierStylePara elsevierViewall">Las tasas globales de detecci&#243;n de CaP &#40;BxI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BxS&#41; fueron del 40&#44;9&#37; &#40;123&#47;301&#41; en el brazo PCA3&#40;&#43;&#41; y del 14&#44;7&#37; &#40;79&#47;537&#41; en el PCA3&#40;&#8211;&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46; Cuando solo se tuvo en cuenta CaP cl&#237;nicamente significativo&#44; 77 y 49 casos fueron detectados entre pacientes PCA3&#40;&#43;&#41; y PCA3&#40;&#8211;&#41;&#44; respectivamente&#46; Si referimos estas cifras a las poblaciones PCA3&#40;&#43;&#41; y PCA3&#40;&#8211;&#41; totales&#44; las tasas de detecci&#243;n de CaP cl&#237;nicamente significativo fueron del 25&#44;6 y 9&#44;1&#37;&#44; respectivamente &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discusi&#243;n</span><p id="par0090" class="elsevierStylePara elsevierViewall">Es un hecho bien sabido que la revisi&#243;n implica sobrediagn&#243;stico<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">14</span></a>&#46; En un estudio epidemiol&#243;gico espa&#241;ol&#44; el 40&#37; del CaP detectado fue CaP de bajo riesgo y mayormente detectado por revisi&#243;n oportunista<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">15</span></a>&#44; reflejando un problema sociodemogr&#225;fico real para las autoridades sanitarias&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Actualmente&#44; las gu&#237;as cl&#237;nicas de la EAU ofrecen el PCA3 como una herramienta potencial para ofrecer una evaluaci&#243;n de riesgo adicional en hombres asintom&#225;ticos con PSA entre 2-10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml para decidir BxI con una recomendaci&#243;n de grado C y un nivel de evidencia de 3&#44; pero no recomendado por la NCCN como una prueba refleja para ganar especificidad para las decisiones de BxI&#46; El corte &#243;ptimo de PCA3 no se ha evaluado prospectivamente en un escenario oportunista aleatorizado<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">16&#44;17</span></a>&#46; PCA3 se ha probado con un corte de 10 en un estudio piloto en la secci&#243;n holandesa del ERSPC como biomarcador de primera l&#237;nea comparado con PSA&#44; pero&#44; con un corte tan bajo&#44; el ABC para la detecci&#243;n de CaP fue de 0&#44;64 para PCA3 vs&#46; 0&#44;58 para PSA &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;143&#41; y casi el 75&#37; de los hombres fueron finalmente biopsiados<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Con una mediana de seguimiento de 21&#44;7 meses&#44; las tasas de detecci&#243;n de CaP mostraron mayores diferencias entre los brazos PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35 y PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35 &#40;40&#44;9 vs&#46; 14&#44;7&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Centr&#225;ndonos en la BxI&#44; la inclusi&#243;n de PCA3 en el corte de 35 como un biomarcador de segunda l&#237;nea podr&#237;a ahorrar potencialmente el 64&#44;1&#37; de BxI &#40;similar al 65&#44;7&#37; en nuestro informe anterior<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">8</span></a>&#41;&#44; pero a un costo de perder 97 CaP estimados &#40;97&#47;537&#44; 18&#44;1&#37; de los hombres con PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&#41; y 56 CaP estimados cl&#237;nicamente significativos &#40;56&#47;537&#44; 10&#44;4&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#sec0065">tabla <span class="elsevierStyleSmallCaps">IV</span> del material suplementario</a>&#41;&#46; As&#237; que en hombres PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&#44; un seguimiento cercano ser&#237;a obligatorio y criterios de BxS estrictos como los nuestros deben ser tenidos en cuenta en un escenario de cribado oportunista&#44; como lo observamos en los hombres con PCA &#60;<span class="elsevierStyleHsp" style=""></span>35 asignados al azar a observaci&#243;n&#44; en quienes CaP cl&#237;nicamente significativo se detecta en el 6&#44;4&#37; durante el seguimiento &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#44; con el seguimiento dado&#46; Creemos que todos estos datos deben darse a todos los hombres sanos con TR normal y PSA &#8805;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; junto con los da&#241;os reconocidos de Bx<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">2-5</span></a> para ayudarles en su decisi&#243;n de someterse a BxI o a un seguimiento cerrado en el caso de PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Hay varias limitaciones en nuestro estudio&#46; En primer lugar&#44; el per&#237;odo de inscripci&#243;n y la mediana de seguimiento son todav&#237;a demasiado cortos&#46; En segundo lugar&#44; si hubi&#233;ramos utilizado ERSPC RC-3 con nuestro grupo de estudio<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">19</span></a>&#44; la BxI podr&#237;a haber sido evitada en 642 hombres &#40;76&#44;6&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#44; reduciendo claramente los costos&#44; pero estimamos 152 casos de falsos negativos&#46; Sin embargo&#44; entre estos&#44; 78 ten&#237;an PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35&#44; 48 de ellos CaP cl&#237;nicamente significativo&#46; Los 74 restantes habr&#237;an tenido PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&#44; 41 de ellos CaP cl&#237;nicamente significativo &#40;<a class="elsevierStyleCrossRef" href="#sec0065">tablas <span class="elsevierStyleSmallCaps">III</span> y <span class="elsevierStyleSmallCaps">IV</span> del material suplementario</a>&#41;&#46; Por &#250;ltimo&#44; entre los PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&#44; se realiz&#243; en un tiempo medio de 11 meses debido a razones log&#237;sticas&#44; pero esto podr&#237;a estar claramente acortado&#44; siendo un marco de tiempo aceptable para detectar la mayor parte de CaP cl&#237;nicamente significativos que no se habr&#237;an detectado si no se hubieran realizado biopsias en pacientes con PCA3&#60;<span class="elsevierStyleHsp" style=""></span>35&#46; Tambi&#233;n nos damos cuenta de que repetir PSA en un plazo razonable antes de la prueba de PCA3 podr&#237;a ser una manera de disminuir su uso<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">20</span></a>&#44; pero los hombres con antecedentes recientes de infecciones del tracto urinario no fueron aceptados con el fin de minimizar este sesgo potencial&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Con el seguimiento real&#44; ninguna evidencia ha confirmado el valor pron&#243;stico de PCA3 b&#225;sicamente por 3 razones&#46; En primer lugar&#44; se observ&#243; una tendencia hacia una mayor puntuaci&#243;n de Gleason &#8805;<span class="elsevierStyleHsp" style=""></span>7 para los tumores en BxI en el brazo PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35&#44; aunque estas diferencias no fueron estad&#237;sticamente significativas &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; En segundo lugar&#44; no se encontraron diferencias entre el n&#250;mero de cilindros afectados para el porcentaje de CaP dentro de los n&#250;cleos entre pacientes PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35 y PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&#46; Por &#250;ltimo&#44; el valor de PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35 no excluy&#243; el riesgo de albergar tumores Gleason &#8805;<span class="elsevierStyleHsp" style=""></span>7 durante el seguimiento&#46; Nuestros resultados son ligeramente peores que el 1&#37; descrito de CaP de alto grado &#40;CaPAG&#41; no detectado al agregar PCA3 al mejor juicio cl&#237;nico en un escenario de repetici&#243;n de Bx y rango de PSA de 2&#44;5-10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">21</span></a>&#46; Tampoco fue encontrado ning&#250;n enlace entre PCA3 y CaPAG por otros investigadores<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">22</span></a>&#46; Nuevos biomarcadores s&#233;ricos como el 4Kscore<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">23</span></a> o el PHI<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">24</span></a>&#44; la detecci&#243;n combinada de PCA3 y TMPRSS2-ERG en la orina<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">25&#44;26</span></a> y otros paneles de biomarcadores m&#250;ltiples necesitan pruebas prospectivas en ensayos aleatorizados<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">27-29</span></a>&#46; Tal vez todos ellos deben ser confrontados o analizados en conjunto a RMmp&#46; Los nomogramas de BxI basados en PCA3 superaron significativamente los modelos cl&#237;nicos sin PCA3 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a>&#44; no detectando solo el 2&#37; de CaPAG y este nomograma ha sido validado externamente por nosotros<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">30</span></a> y otros<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">31</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Para concluir&#44; se muestran los resultados prospectivos y de la vida real de la utilizaci&#243;n de PCA3 como una sola variable a&#241;adida en un escenario de detecci&#243;n oportunista&#46; Si se utiliza PCA3 en un corte 35 como biomarcador de segunda l&#237;nea despu&#233;s de PSA &#8805;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml y un TR normal&#44; puede potencialmente evitarse el 64&#37; de BxI&#44; solo el 12&#44;5&#37; menos que con ERSPC RC-3&#44; sin embargo&#44; se reduce la tasa de falsos negativos en un 36&#44;2&#37;&#46; En un seguimiento de 21&#44;7 meses&#44; este doble protocolo muestra claramente que si PCA3 es menor de 35 y no se realiza BxI con un TR normal y un PSA &#8805;<span class="elsevierStyleHsp" style=""></span>3&#44; un seguimiento cercano es obligatorio y una BxS temprana recomendable dependiendo de los criterios de cin&#233;tica de PSA&#44; debido al 10&#44;4&#37; de los resultados falsos negativos del PCA3 para la detecci&#243;n cl&#237;nica significativa del CaP en el escenario BxI y al 9&#44;1&#37; con el seguimiento dado&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Financiaci&#243;n</span><p id="par0120" class="elsevierStylePara elsevierViewall">Este trabajo ha sido apoyado por las becas PI061619&#44; PI101206 del Instituto Carlos <span class="elsevierStyleSmallCaps">III</span> &#40;Madrid&#44; Espa&#241;a&#41; y por la ACOMP&#47;2009&#47;176 de la Generalitat Valenciana&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicto de intereses</span><p id="par0125" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objetivos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Determinar el comportamiento del PCA3 como un marcador de segunda l&#237;nea en un programa de cribado oportunista de c&#225;ncer de pr&#243;stata &#40;CaP&#41; y su comparaci&#243;n con la calculadora de riesgo 3 del cribado aleatorizado europeo en c&#225;ncer de pr&#243;stata &#40;ERSPC RC-3&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Un total de 5&#46;199 hombres de 40-75 a&#241;os se hicieron la prueba del ant&#237;geno prost&#225;tico espec&#237;fico &#40;PSA&#41; y un tacto rectal &#40;TR&#41;&#46; Aquellos con TR normal y PSA &#8805;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml se realizaron un PCA3&#46; Todos los hombres con PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35 se hicieron biopsia inicial &#40;BxI&#41; &#8212;12 cilindros&#8212;&#46; Aquellos con PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35 se aleatorizaron 1&#58;1 a BxI u observaci&#243;n&#46; Los resultados se comparan con los obtenidos con la aplicaci&#243;n de la calculadora ERSPC RC-3&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">PCA3 se test&#243; en 838 hombres &#40;16&#44;1&#37;&#41;&#46; En los grupos PCA3&#40;&#43;&#41; y PCA3&#40;&#8211;&#41;&#44; las tasas de detecci&#243;n global de CaP fueron del 40&#44;9 y del 14&#44;7&#37; a una mediana de seguimiento de 21&#44;7 meses &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#46; En el grupo PCA3&#40;&#43;&#41; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>301&#44; 35&#44;9&#37;&#41;&#44; se identific&#243; CaP en 115 hombres en BxI &#40;38&#44;2&#37;&#41;&#46; En el brazo aleatorizado&#44; 256 se hicieron BxI y se objetiv&#243; CaP en 46 &#40;18&#44;0&#37;&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; La potencial tasa de ahorro de biopsias siguiendo el corte PCA3<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>35 hubiera sido de 64&#44;1&#37; frente a la de 76&#44;6&#37; si hubi&#233;ramos usado ERSPC RC-3&#46; Sin embargo&#44; la tasa estimada de falsos negativos de CaP de alto grado &#40;CaPAG<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Gleason &#8805;<span class="elsevierStyleHsp" style=""></span>7&#41; se hubiera reducido un 37&#44;1&#37; &#40;de 89 a 56 pacientes&#41; al usar el PCA3&#46; Si hubi&#233;ramos usado el corte 35 de PCA3 para no realizar BxI&#44; hubi&#233;semos dejado de diagnosticar un 14&#44;7&#37; de CaP y un 9&#44;1&#37; de CaP cl&#237;nicamente significativo&#44; a un seguimiento medio aproximado de 2 a&#241;os&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Cuando se usa PCA3-35 como biomarcador de segunda l&#237;nea en hombres con PSA &#8805;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml y TR normal&#44; se puede obviar la BxI un 12&#44;5&#37; menos que usando la ERSPC RC-3&#44; pero reduciendo los falsos negativos un 36&#44;2&#37;&#46; A un seguimiento de 21&#44;7 meses&#44; este protocolo dual no hubiera detectado un 9&#44;1&#37; de CaP cl&#237;nicamente significativo&#44; por lo que el seguimiento con estrictos criterios de biopsia basados en PSA y TR es obligatorio en casos con PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objectives</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">PCA3 performance as a single second line biomarker is compared to the European Randomised Study of Screening for Prostate Cancer risk calculator model 3 &#40;ERSPC RC-3&#41; in an opportunistic screening in prostate cancer &#40;PCa&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">5&#44;199 men&#44; aged 40-75y&#44; underwent prostate-specific antigen &#40;PSA&#41; screening and digital rectal examination &#40;DRE&#41;&#46; Men with a normal DRE and PSA &#8805;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml had a PCA3 test done&#46; All men with PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35 underwent an initial biopsy &#40;IBx&#41; &#8212;12 cores&#8212;&#46; Men with PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35 were randomized 1&#58;1 to either IBx or observation&#46; We compared them to those obtained with ERSPC RC-3&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">PCA3 test was performed on 838 men &#40;16&#46;1&#37;&#41;&#46; In PCA3&#40;&#43;&#41; and PCA3&#40;&#8211;&#41; groups&#44; global PCa detection rates were 40&#46;9&#37; and 14&#46;7&#37; with a median follow-up &#40;FU&#41; of 21&#46;7 months &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; In the PCA3&#40;&#43;&#41; arm &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>301&#44; 35&#46;9&#37;&#41;&#44; PCa was identified in 115 men at IBx &#40;38&#46;2&#37;&#41;&#46; In the randomized arm&#44; 256 underwent IBx and PCa was found in 46 &#40;18&#46;0&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; The biopsy-sparing potential would have been 64&#46;1&#37; as opposed to 76&#46;6&#37; if we had used ERSPC RC-3&#46; However&#44; the estimated false negative cases for HGPCa would have been reduced by 37&#46;1&#37; &#40;89 to 56 patients&#41;&#46; Moreover&#44; if we had applied PCA3-35 to avoid IBx&#44; 14&#46;7&#37; PCa and 9&#46;1&#37; of clinical significant PCa patients would not have been diagnosed during this FU&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">When PCA3-35 is used as a second-line biomarker when PSA &#8805;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml and DRE is normal&#44; IBx could be avoided in 12&#46;5&#37; less than if ERSPC RC-3 is used and would reduce the false negative cases by 36&#46;2&#37;&#46; At a FU of 21&#46;7 months&#44; this dual protocol would miss 9&#46;1&#37; of clinically significant PCa&#44; so strict FU is mandatory with established biopsy criteria based on PSA and DRE in cases with PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objectives"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Material and methods"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusions"
          ]
        ]
      ]
    ]
    "apendice" => array:1 [
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        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0140" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Anexo A"
            "titulo" => "Material suplementario"
            "identificador" => "sec0065"
          ]
        ]
      ]
    ]
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        "etiqueta" => "Figura 1"
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Algoritmo del protocolo y resultados&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#42; Pacientes sometidos a aleatorizaci&#243;n&#44; donde 13 hombres con PCA3 &#60; 35 inicialmente asignados al azar al brazo de biopsia lo rechazaron y se incluyeron en el brazo de observaci&#243;n&#46;</p>"
        ]
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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            "imagen" => "gr2.jpeg"
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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">&#193;reas bajo la curva obtenidas para el PCA3&#44; la calculadora de riesgo 3 del ERSPC y la del modelo obtenido en nuestra serie PSE&#44; PCA3 y tacto rectar&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figura 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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        "descripcion" => array:1 [
          "es" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Curvas de beneficio neto obtenidas para el PCA3&#44; la calculadora de riesgo 3 del ERSPC y la del modelo obtenido en nuestra serie con PSA&#44; PCA3 y tacto rectal&#46;</p>"
        ]
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">PSA&#58; ant&#237;geno prost&#225;tico espec&#237;fico&#59; CaP&#58; c&#225;ncer de pr&#243;stata&#59; DE&#58; desviaci&#243;n est&#225;ndar&#59; ERSPC RC-3&#58; modelo de calculadora de riesgo 3 del cribado aleatorizado europeo en c&#225;ncer de pr&#243;stata&#59; RIC&#58; rango intercuartil&#59; TR&#58; tacto rectal&#46;</p>"
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                  <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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">N&#250;mero de pacientes</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">838 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">537 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">301 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Edad</span></td><td class="td" title="table-entry  " align="char" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&#44;7 &#40;6&#44;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#44;8 &#40;6&#44;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&#44;4 &#40;5&#44;78&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;RIC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62 &#40;57-66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61 &#40;56-66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64 &#40;60-68&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Familiares con CaP</span></td><td class="td" title="table-entry  " align="char" valign="top">0&#44;070&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">693 &#40;82&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">454 &#40;84&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">239 &#40;79&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">145 &#40;17&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83 &#40;15&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62 &#40;20&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">PSA</span></td><td class="td" title="table-entry  " align="char" valign="top">0&#44;156&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#44;49 &#40;1&#44;99&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#44;42 &#40;1&#44;79&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;62 &#40;2&#44;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;RIC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#44;9 &#40;3&#44;3-4&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#44;9 &#40;3&#44;3-4&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#44;0 &#40;3&#44;3-4&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">TR</span></td><td class="td" title="table-entry  " align="char" valign="top">0&#44;651&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adenoma <span class="elsevierStyleSmallCaps">I</span>-<span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">673 &#40;80&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">434 &#40;80&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">239 &#40;79&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adenoma <span class="elsevierStyleSmallCaps">III</span>-<span class="elsevierStyleSmallCaps">IV</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">165 &#40;19&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">103 &#40;19&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62 &#40;20&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">ERSPC RC-3</span></td><td class="td" title="table-entry  " align="char" valign="top">0&#44;313&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#44;6 &#40;8&#44;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#44;4 &#40;7&#44;94&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#44;0 &#40;8&#44;97&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;RIC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#44;6 &#40;11&#44;1-18&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#44;5 &#40;11&#44;1-18&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#44;8 &#40;11&#44;2-18&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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          "es" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas del grupo de estudio &#40;hombres que entraron en el protocolo dual con prueba de PCA3&#41; CaP&#47;147</p>"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">BxI&#58; biopsia inicial&#59; CaP&#58; c&#225;ncer de pr&#243;stata&#59; DE&#58; desviaci&#243;n est&#225;ndar&#59; RIC&#58; rango intercuartil&#46;</p>"
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                  <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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PCA3 &#60;<span class="elsevierStyleHsp" style=""></span>35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PCA3 &#8805;<span class="elsevierStyleHsp" style=""></span>35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">N&#250;mero de BxI</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">256&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">301&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">CaP</span></td><td class="td" title="table-entry  " align="char" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">210 &#40;82&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">186 &#40;61&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46 &#40;18&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">115 &#40;38&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">N&#250;mero de BxI positivas</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">115&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Cilindros positivos</span></td><td class="td" title="table-entry  " align="char" valign="top">0&#44;843&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#44;00 &#40;2&#44;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#44;08 &#40;2&#44;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;RIC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;0 &#40;1&#44;0-4&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;0 &#40;1&#44;0-4&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Puntuaci&#243;n de Gleason</span></td><td class="td" title="table-entry  " align="char" valign="top">0&#44;211&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32 &#40;69&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66 &#40;57&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;30&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49 &#40;42&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">&#37; de CaP en los n&#250;cleos</span></td><td class="td" title="table-entry  " align="char" valign="top">0&#44;772&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&#44;9 &#40;18&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#44;9 &#40;18&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;RIC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#44;7 &#40;10&#44;0-33&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#44;7 &#40;9&#44;1-33&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1750674.png"
              ]
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        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas de BxI</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabla 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">En negrita se resaltan los estad&#237;sticos para el PCA3 mayor o igual a 35 como se testa en nuestro protocolo y los de la calculadora n&#46;&#176;3 del ERSPC&#46;</p><p id="spar9045" class="elsevierStyleSimplePara elsevierViewall">BxI&#58; biopsia inicial&#59; ERSPC RC-3&#58; modelo de calculadora de riesgo 3 del cribado aleatorizado europeo en c&#225;ncer de pr&#243;stata&#59; PPI&#58; ponderaci&#243;n de probabilidad inversa&#46;</p><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Falsos negativos estimados para todos los pacientes &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>838&#41; utilizando el m&#233;todo PPI&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sensibilidad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Especificidad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Valor predictivo positivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Valor predictivo negativo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N&#250;mero de BxI<br>n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimaci&#243;n de falsos negativos<br>n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PCA3 &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">87&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">450 &#40;53&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50 &#40;6&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PCA3 &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">68&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">84&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">393 &#40;46&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67 &#40;8&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PCA3 &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">330 &#40;39&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">86 &#40;10&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">PCA3 &#40;&#8805;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">35&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">54&#44;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">70&#44;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">38&#44;2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">81&#44;9</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">301 &#40;35&#44;9&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">97 &#40;11&#44;6&#41;</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="table-entry ; entry_with_role_rowhead " align="left" valign="top">PCA3 &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">74&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">82&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">270 &#40;32&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">102 &#40;12&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">ERSPC RC-3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">28&#44;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">78&#44;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">30&#44;6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">76&#44;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">196 &#40;23&#44;4&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">152 &#40;18&#44;1&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "es" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Sensibilidad corregida&#44; especificidad&#44; valor predictivo positivo y valor predictivo negativo para diferentes valores de PCA3 y criterio de biopsia ERSPC RC-3</p>"
        ]
      ]
      6 => array:8 [
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        "etiqueta" => "Tabla 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">PSA&#58; ant&#237;geno prost&#225;tico espec&#237;fico&#59; BxI&#58; biopsia inicial&#59; CaP&#58; c&#225;ncer de pr&#243;stata&#59; IC&#58; intervalo de confianza&#59; LN&#58; logaritmo natural&#59; OR&#58; <span class="elsevierStyleItalic">odds ratio</span>&#59; TR&#58; tacto rectal&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                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="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Modelo univariable</th><th class="td" title="table-head  " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Modelo multivariable</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">IC 95&#37;</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">IC 95&#37;</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Familiares con CaP</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;230&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">&#40;l&#237;nea basal&#41;</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;318&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;840&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;070&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Edad</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;975&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;036&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;745&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Volumen de TR</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;040&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>cc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">&#40;l&#237;nea basal&#41;</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>cc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;689&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;789&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;986&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;169&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#44;372&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">LN &#40;PSA&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;076&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;225&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#44;517&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;116&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;210&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#44;702&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">LN &#40;PCA3&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;066&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;675&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;548&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;110&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;705&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;612&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  <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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BxI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BxS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Global<br>n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">CaP</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">PCA3 &#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">35</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">537&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">79 &#40;14&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Aleatorizaci&#243;n a observaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">281&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28 &#40;10&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Aleatorizaci&#243;n a BxI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">256&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51 &#40;19&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">PCA3 &#8805;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">35</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">301&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">115&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">123 &#40;40&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">CaP cl&#237;nicamente significativo</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">PCA3 &#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">35</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">537&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49 &#40;9&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Aleatorizaci&#243;n a observaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">281&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18 &#40;6&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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