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Papel de PCA3 y SelectMDx en la optimización de la vigilancia activa en el cáncer de próstata
Role of PCA3 and SelectMDx in the optimization of active surveillance in prostate cancer
D. Fiorellaa,◊, J.L. Marencoa, J.M. Mascarósa, A. Borque-Fernandob, L.M. Estebanc, A. Calatravad, B. Pastore, J.A. López-Guerreroe,f,g, J. Rubio-Brionesa,◊,
Autor para correspondencia
jrubio@fivo.org

Autor para correspondencia.
a Departamento de Urología, Instituto Valenciano de Oncología, Valencia, España
b Departamento de Urología, IIS-Aragón, Hospital Universitario Miguel Servet, Zaragoza, España
c Departamento de Matemáticas Aplicadas, Escuela Universitaria Politécnica de La Almunia, Universidad de Zaragoza, La Almunia de Doña Godina, Zaragoza, España
d Departamento de Patología, Instituto Valenciano de Oncología, Valencia, España
e Laboratorio de Biología Molecular, Instituto Valenciano de Oncología, Valencia, España
f IVO-CIPF Joint Research Unit of Cancer, Centro de Investigación Príncipe Felipe (CIPF), Valencia, España
g Departamento de Patología, Facultad de Medicina, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain
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            "entidad" => "IVO-CIPF Joint Research Unit of Cancer&#44; Centro de Investigaci&#243;n Pr&#237;ncipe Felipe &#40;CIPF&#41;&#44; Valencia&#44; Espa&#241;a"
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            "entidad" => "Departamento de Patolog&#237;a&#44; Facultad de Medicina&#44; Universidad Cat&#243;lica de Valencia San Vicente M&#225;rtir&#44; Valencia&#44; Spain"
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        "titulo" => "Role of PCA3 and SelectMDx in the optimization of active surveillance in prostate cancer"
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          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">a&#41;<span class="elsevierStyleHsp" style=""></span>Curvas de Kaplan-Meyer para la supervivencia libre de progresi&#243;n patol&#243;gica basadas en un punto de corte de SelectMDx de 5&#46; b&#41;<span class="elsevierStyleHsp" style=""></span>Punto de corte de 65 para PCA3&#46; c&#41;<span class="elsevierStyleHsp" style=""></span>Curvas de Kaplan-Meyer para la supervivencia libre de progresi&#243;n patol&#243;gica con base a un riesgo bajo y alto&#46;</p>"
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    "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">El cribado del c&#225;ncer de pr&#243;stata &#40;CaP&#41; demostr&#243; una disminuci&#243;n de la mortalidad en los resultados de 16<span class="elsevierStyleHsp" style=""></span>a&#241;os de seguimiento del <span class="elsevierStyleItalic">European Randomized study of Screening for Prostate Cancer</span> &#40;ERSPC&#41;&#59; para salvar una vida se necesitaron 570 varones sometidos a cribado y 18 diagnosticados<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a>&#46; Para mejorar la detecci&#243;n del CaP cl&#237;nicamente significativo se ha investigado y validado el uso de biomarcadores en suero y orina<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2-4</span></a>&#46; Sin embargo&#44; el papel de los biomarcadores en el diagn&#243;stico del CaP se ha visto superado en gran medida por la resonancia magn&#233;tica multiparam&#233;trica &#40;RMmp&#41;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a>&#46; Con el objetivo de evitar el sobretratamiento del CaP indolente&#44; la vigilancia activa &#40;VA&#41; es una opci&#243;n de tratamiento recomendada en todas las directrices<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a>&#44; y est&#225; especialmente respaldada por la baja mortalidad espec&#237;fica por c&#225;ncer en el seguimiento a largo plazo de los CaP de bajo riesgo<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Del mismo modo que la RMmp se evalu&#243; inicialmente para el diagn&#243;stico del CaP y luego se aplic&#243; para el seguimiento del CaP de bajo grado<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a>&#44; tambi&#233;n se ha investigado el papel de los biomarcadores para predecir la reclasificaci&#243;n durante la VA&#46; Es el caso de las pruebas s&#233;ricas 4KScore&#174; y <span class="elsevierStyleItalic">Prostate Health Index</span> &#40;PHI&#41;&#44; que ayudan a identificar a los varones con mayor riesgo de ser reclasificados en la biopsia confirmatoria<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a>&#46; Adem&#225;s&#44; las pruebas Oncotype Dx Genomic Prostate Score&#174; &#40;GPS&#41;&#44; Prolaris&#174; y Decipher&#174; predijeron caracter&#237;sticas patol&#243;gicas adversas en la muestra de prostatectom&#237;a radical<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a>&#46; Por otro lado&#44; los niveles de PCA3 en orina no se correlacionaron con el riesgo de reclasificaci&#243;n a corto plazo<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a>&#46; Existen otros kits con resultados potencialmente prometedores&#59; aunque no est&#225;n disponibles comercialmente&#44; est&#225;n siendo estudiados en una fase de investigaci&#243;n temprana<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#44;13</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Nuestro objetivo es evaluar el papel de PCA3 y SelectMDx&#44; obtenidos antes del diagn&#243;stico de CaP o de la biopsia confirmatoria una vez que se ha sugerido la VA&#44; para predecir la supervivencia libre de progresi&#243;n patol&#243;gica &#40;SLPP&#41; en biopsias de seguimiento posteriores en una cohorte de VA de un solo centro&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material y m&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">Se inscribieron 542 pacientes en un protocolo de VA de un solo centro entre 2009 y 2019&#46; Ochenta y seis de ellos ten&#237;an muestras de orina obtenidas antes del diagn&#243;stico de CaP o durante su periodo de confirmaci&#243;n &#40;antes de la biopsia confirmatoria en los 12<span class="elsevierStyleHsp" style=""></span>meses siguientes&#41; y ten&#237;an los resultados tanto de PCA3 como de SelectMDx&#46; Las muestras de orina se almacenaron a &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C en el Biobanco de nuestro centro&#46; El reclutamiento de pacientes y los procedimientos de toma de muestras se llevaron a cabo siguiendo todos los requisitos normativos y leyes locales&#44; de acuerdo con la Declaraci&#243;n de Helsinki&#44; y tras la aprobaci&#243;n de nuestro Comit&#233; de &#201;tica &#40;CAPROSIVO&#44; PROMETEO&#47;2016&#47;103&#41; en mayo de 2015&#46; Todos los pacientes firmaron un consentimiento informado por escrito antes de entrar en el estudio&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Los criterios de selecci&#243;n para la inclusi&#243;n en VA fueron una esperanza de vida superior a 10<span class="elsevierStyleHsp" style=""></span>a&#241;os&#44; estadio<span class="elsevierStyleHsp" style=""></span>cT1&#44; grupo de grado &#91;GG&#93;<span class="elsevierStyleHsp" style=""></span>I &#40;Gleason 3&#43;3&#41;&#44; PSA &#8804;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; densidad del PSA &#40;PSAd&#41; &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; &#8804;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>n&#250;cleos positivos con menos del 50&#37; de afectaci&#243;n del c&#225;ncer o &#60;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>mm de longitud&#46; Tambi&#233;n se acept&#243; para VA a los varones mayores de 70<span class="elsevierStyleHsp" style=""></span>a&#241;os con GG<span class="elsevierStyleHsp" style=""></span>II &#40;3&#43;4&#41; con menos del 10&#37; de Gleason<span class="elsevierStyleHsp" style=""></span>4 y sin ninguna variable adicional de las anteriormente mencionadas para los pacientes con GG<span class="elsevierStyleHsp" style=""></span>I&#46; Se excluyeron para el an&#225;lisis los varones que recibieron una biopsia confirmatoria despu&#233;s de 12<span class="elsevierStyleHsp" style=""></span>meses desde el inicio en VA&#46; Ning&#250;n paciente tomaba inhibidores de la 5-&#945;-reductasa&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Las muestras de orina &#40;20-30<span class="elsevierStyleHsp" style=""></span>ml&#41; se recogieron despu&#233;s de un examen rectal digital &#40;ERD&#41; estandarizado siguiendo las recomendaciones para el test PCA3 <span class="elsevierStyleItalic">&#40;Physician Brochure for the PRoGensa</span>&#174; <span class="elsevierStyleItalic">PCA3&#41;</span>&#46; Se procesaron 2&#44;5<span class="elsevierStyleHsp" style=""></span>ml utilizando el kit de transporte de muestras de orina Progensa PCA3 &#40;Hologic Inc&#44; San Diego&#41; y posteriormente se almacenaron a &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C en nuestro Biobanco&#46; Para el an&#225;lisis de SelectMDx se envi&#243; un conjunto piloto de 30 muestras en hielo seco al laboratorio de pruebas &#40;MDxHealth&#44; SA&#44; Nijmegen&#44; NL&#41; para verificar la estabilidad del ARN mensajero &#40;ARNm&#41; y asegurar la validez de los resultados del ensayo&#46; MDxHealth proporcion&#243; puntuaciones de riesgo basadas en el an&#225;lisis del ARNm en la orina&#44; sin tener en cuenta los resultados de la biopsia&#46; La prueba midi&#243; los niveles de ARNm de los genes DLX1 y HOXC6 en una muestra de orina posterior al ERD y los combin&#243; con el PSA s&#233;rico&#44; el PSAd&#44; el estado del ERD&#44; la edad y los antecedentes familiares de CaP<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">El volumen total de la pr&#243;stata derivado de la ecograf&#237;a transrectal se calcul&#243; mediante la f&#243;rmula del elipsoide &#40;0&#44;52 &#215;<span class="elsevierStyleHsp" style=""></span>longitud &#215;<span class="elsevierStyleHsp" style=""></span>anchura &#215;<span class="elsevierStyleHsp" style=""></span>altura&#41;&#46; En la biopsia transrectal ecodirigida inicial se tomaron de 10 a 12 n&#250;cleos de manera sistem&#225;tica&#46; La biopsia confirmatoria consisti&#243; en la obtenci&#243;n transperineal de 30 n&#250;cleos m&#225;s n&#250;cleos dirigidos en caso de haber identificado zonas sospechosas en la RMmp&#46; Todas las muestras de biopsia fueron evaluadas por un &#250;nico uropat&#243;logo experimentado &#40;AC&#41;&#46; En esta cohorte no se realiz&#243; RMmp de manera rutinaria debido al periodo de inclusi&#243;n&#59; se incluy&#243; la puntuaci&#243;n PIRADS-v2 cuando estaba disponible&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lisis estad&#237;stico</span><p id="par0040" class="elsevierStylePara elsevierViewall">El objetivo principal del estudio fue evaluar el impacto de PCA3 y SelectMDx&#44; de forma individual y combinada&#44; en la predicci&#243;n de la progresi&#243;n patol&#243;gica&#44; definida como un aumento del Grupo de Grado o por el aumento del volumen del CaP &#40;&#62;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>n&#250;cleos positivos y &#62;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>zonas prost&#225;ticas afectadas en la biopsia transperineal&#41; o cualquier n&#250;cleo con &#62;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>mm o &#62;<span class="elsevierStyleHsp" style=""></span>50&#37; de afectaci&#243;n&#44; independientemente del GG&#46; Se realizaron an&#225;lisis univariantes y multivariantes para correlacionar las puntuaciones de PCA3 y SelectMDx&#44; as&#237; como variables cl&#237;nicas y patol&#243;gicas como la edad&#44; el PSAd&#44; el ERD&#44; la puntuaci&#243;n de Gleason en el momento del diagn&#243;stico y la puntuaci&#243;n PIRADS&#44; cuando estaba disponible&#44; con la progresi&#243;n patol&#243;gica &#40;PP&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Se utiliz&#243; la prueba de chi cuadrado para comparar las variables categ&#243;ricas&#46; Para la comparaci&#243;n de las variables continuas se utiliz&#243; la prueba t de Student cuando se pudo aceptar la normalidad y la prueba U de Mann-Whitney en el caso contrario&#46; Se utilizaron curvas de Kaplan-Meier para el an&#225;lisis de la supervivencia y la prueba de Log-Rank para comparar grupos&#46; Cuando fue posible&#44; se aplicaron modelos de regresi&#243;n de riesgos proporcionales de Cox para predecir la PP&#46; Se utiliz&#243; la funci&#243;n step para seleccionar el mejor modelo seg&#250;n el criterio de informaci&#243;n de Akaike &#40;AIC&#41;&#46; La capacidad de discriminaci&#243;n se estim&#243; mediante el &#237;ndice<span class="elsevierStyleHsp" style=""></span>C&#46; Se estimaron las sensibilidades&#44; las especificidades y los valores predictivos positivos y negativos a los 5<span class="elsevierStyleHsp" style=""></span>a&#241;os de seguimiento&#46; Para establecer el punto de corte &#171;&#243;ptimo&#187; para los biomarcadores se utiliz&#243; el &#237;ndice de Youden<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a>&#46; Se utilizaron pruebas bilaterales con un nivel de significaci&#243;n del 5&#37;&#46; El an&#225;lisis de los datos se realiz&#243; con el lenguaje de programaci&#243;n R v&#46;<span class="elsevierStyleHsp" style=""></span>3&#46;6&#46;3 &#40;The R Foundation for Statistical Computing&#44; Viena&#44; Austria&#41;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a>&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><p id="par0050" class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> muestra las caracter&#237;sticas cl&#237;nicas de nuestros 86 pacientes seleccionados&#46; El seguimiento medio de estos pacientes desde su diagn&#243;stico de CaP fue de 69&#44;2<span class="elsevierStyleHsp" style=""></span>meses &#40;desviaci&#243;n est&#225;ndar&#58; 25&#44;7<span class="elsevierStyleHsp" style=""></span>meses&#41;&#44; con una mediana de 69&#44;92 &#40;rango&#58; 48-91&#41; meses&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Durante el primer a&#241;o de seguimiento solo 7 pacientes no recibieron una biopsia confirmatoria por diversos motivos &#40;biopsia inicial transperineal en un caso y preferencias del paciente o enfermedades intercurrentes que lo desaconsejaban en el resto&#41;&#59; 20 de 79 &#40;25&#44;32&#37;&#41; fueron reclasificados en la biopsia confirmatoria&#46; En el estudio univariante&#44; ninguna de las siguientes mostr&#243; diferencias estad&#237;sticamente significativas en cuanto a la reclasificaci&#243;n en la biopsia confirmatoria&#58; la edad&#44; el PSAd&#44; el ERD&#44; el PCA3&#44; el SelectMDx&#44; la puntuaci&#243;n de Gleason ni la clasificaci&#243;n PIRADS&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Independientemente del tiempo hasta la realizaci&#243;n de la biopsia&#44; los 86 pacientes recibieron al menos una biopsia despu&#233;s del inicio en VA&#59; 41 pacientes &#40;47&#44;67&#37;&#41; recibieron una biopsia&#44; 30 pacientes &#40;34&#44;88&#37;&#41; recibieron dos y 15 pacientes &#40;17&#44;44&#37;&#41; tres o m&#225;s biopsias&#46; A los 5<span class="elsevierStyleHsp" style=""></span>a&#241;os&#44; la SLPP fue del 46&#44;48&#37; &#40;intervalo de confianza &#91;IC&#93; del 95&#37;&#58; 36&#44;42-59&#44;32&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">De los 86 pacientes&#44; 45 &#40;52&#44;33&#37;&#41; sufrieron PP&#59; en 43 de ellos la progresi&#243;n ocurri&#243; antes de 5<span class="elsevierStyleHsp" style=""></span>a&#241;os&#46; El an&#225;lisis univariante con las variables mencionadas &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41; mostr&#243; que el SelectMDx se correlacionaba con la PP durante el seguimiento con una hazard ratio &#40;HR&#41; de 1&#44;035 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 1&#44;012-1&#44;057&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;&#46; Como puede observarse en el diagrama de caja &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#44; el valor mediano del SelectMDx fue el doble para el grupo que present&#243; PP &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#44; obteniendo un valor en el &#237;ndice<span class="elsevierStyleHsp" style=""></span>C de Harrel de 0&#44;670 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 0&#44;529-0&#44;810&#41;&#46; Utilizando la funci&#243;n STEP&#44; SelectMDx y PCA3 obtuvieron las mejores cifras en comparaci&#243;n con las diferentes combinaciones del resto de las variables&#44; pero PCA3 se mantiene sin significaci&#243;n estad&#237;stica en el modelo&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Utilizando el &#237;ndice de Youden&#44; el punto de corte &#171;&#243;ptimo&#187; de SelectMDx para la PP fue 5&#46; La <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a> muestra la asociaci&#243;n de SelectMDx en este punto de corte con la tasa de PP a los 5<span class="elsevierStyleHsp" style=""></span>a&#241;os&#44; dando como resultado una sensibilidad &#40;S&#41;&#44; una especificidad &#40;E&#41;&#44; un valor predictivo negativo &#40;VPN&#41; y un valor predictivo positivo &#40;VPP&#41; de 69&#44;77 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 53&#44;87-82&#44;82&#41;&#44; 67&#44;44 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 51&#44;46-80&#44;02&#41;&#44; 69&#44;05 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 52&#44;91-82&#44;38&#41; y 68&#44;18 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 52&#44;42-81&#44;39&#41;&#44; respectivamente&#46; Para el PCA3&#44; el punto de corte &#171;&#243;ptimo&#187; se fij&#243; en 65&#44; con una S del 51&#44;16&#37; &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 35&#44;46-66&#44;69&#41;&#44; una E del 74&#44;42&#37; &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 58&#44;83-86&#44;48&#41;&#44; un VPN de 60&#44;38 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 46&#44;00-73&#44;55&#41; y un VPP de 66&#44;67 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 48&#44;17-82&#44;04&#41;&#46; La <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a>a&#44;b muestra las diferencias de la SLPP con base en los puntos de corte de SelectMDx &#62;<span class="elsevierStyleHsp" style=""></span>5 y PCA3 &#62;<span class="elsevierStyleHsp" style=""></span>65&#44; respectivamente&#46; En ambos casos se encontraron diferencias utilizando el test log-rank &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001 y p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#44; respectivamente&#41;&#46; La SLPP estimada a 5<span class="elsevierStyleHsp" style=""></span>a&#241;os para un paciente con un SelectMDx &#62;<span class="elsevierStyleHsp" style=""></span>5 ser&#237;a del 27&#44;57&#37; &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 16&#44;33-46&#44;54&#41;&#44; obteniendo un HR de 3&#44;30 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 1&#44;75-6&#44;24&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Con un punto de corte de la puntuaci&#243;n 10 en SelectMDx&#44; la SLPP estimada a 5<span class="elsevierStyleHsp" style=""></span>a&#241;os habr&#237;a sido del 16&#44;30&#37; &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 5&#44;95-44&#44;71&#41;&#44; con un HR de 3&#44;10 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 1&#44;32-4&#44;36&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Al considerar ambos biomarcadores como una variable combinada&#44; propusimos un modelo de regresi&#243;n de Cox y utilizamos el &#237;ndice de Youden para estudiar la PP en funci&#243;n de las estimaciones de supervivencia obtenidas&#59; as&#237;&#44; se crearon dos grupos&#44; uno de bajo riesgo y otro de alto riesgo&#46; La <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a>c muestra las diferencias en la SLPP con base en los dos grupos&#46; La <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a> muestra las diferencias en la PP con base en los dos grupos&#46; La SLPP estimada a 5<span class="elsevierStyleHsp" style=""></span>a&#241;os para el grupo de alto riesgo fue del 34&#44;82&#37; &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 23&#44;71-51&#44;15&#41;&#44; similar a la obtenida solo con SelectMDx&#44; con un HR de 2&#44;93 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 1&#44;31-6&#44;59&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; Por otro lado&#44; la comparaci&#243;n del AUC para PCA3&#44; SelectMDx&#44; PSA&#44; PSAd y dos calculadoras de riesgo conocidas &#40;ERSPC y PBCG&#41;&#44; creadas para detectar el CaP de alto grado en el entorno del diagn&#243;stico de CaP<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#44;18</span></a>&#44; muestra que SelectMDx report&#243; el mejor AUC&#44; bastante similar al ERSPC-RC &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>a&#41; para predecir la PP a 5<span class="elsevierStyleHsp" style=""></span>a&#241;os&#46; Por &#250;ltimo&#44; la <a class="elsevierStyleCrossRef" href="#fig0015">figura 3</a>b muestra la comparaci&#243;n del &#237;ndice<span class="elsevierStyleHsp" style=""></span>C de Harrel para PCA3&#44; SelectMDx&#44; PSA&#44; PSAd&#44; ERSPC&#44; PBCG y el modelo con SelectMDx y PCA3&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discusi&#243;n</span><p id="par0080" class="elsevierStylePara elsevierViewall">La VA es el enfoque preferido para el tratamiento cl&#237;nico del CaP de bajo y muy bajo riesgo&#44; tal como se indica en las directrices actuales<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a>&#46; A pesar de los rigurosos criterios de selecci&#243;n&#44; se han notificado tasas de aumento en la puntuaci&#243;n de Gleason del 29-34&#37; en las muestras de prostatectom&#237;a radical<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a>&#46; En nuestra propia instituci&#243;n&#44; en toda la cohorte de VA &#40;542 hombres&#41; y con los criterios mencionados&#44; observamos una tasa de PP del 44&#44;42&#37; a 5<span class="elsevierStyleHsp" style=""></span>a&#241;os &#40;datos no publicados&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Por lo tanto&#44; todav&#237;a hay margen de mejora y reducci&#243;n de la reclasificaci&#243;n&#44; especialmente durante el per&#237;odo crucial de selecci&#243;n y confirmaci&#243;n de los pacientes&#44; con el fin de reducir la incertidumbre de los pacientes&#44; el riesgo oncol&#243;gico y optimizar el n&#250;mero de rebiopsias de seguimiento&#44; que&#44; adem&#225;s de ser molestas<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a>&#44; no est&#225;n exentas de complicaciones<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a>&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Los biomarcadores urinarios y s&#233;ricos se han centrado en el diagn&#243;stico del CaP&#44; y &#250;ltimamente en la identificaci&#243;n del CaP de alto grado<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>&#46; Sin embargo&#44; hasta donde sabemos&#44; ninguno de ellos ha sido validado en el contexto de la VA&#46; El test 4KScore&#174; ha sido evaluado como variable predictiva de la PP en la biopsia confirmatoria&#44; demostrando que podr&#237;a evitar el 27&#37; de las biopsias estableciendo un punto de corte del 7&#44;5&#37;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a>&#46; Los biomarcadores tisulares eval&#250;an paneles g&#233;nicos en el n&#250;cleo m&#225;s representativo de la biopsia&#44; prediciendo factores desfavorables en la muestra de prostatectom&#237;a radical<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> y la mortalidad espec&#237;fica por c&#225;ncer a 10<span class="elsevierStyleHsp" style=""></span>a&#241;os<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">10&#44;24</span></a>&#46; Sin embargo&#44; dada la heterogeneidad y la naturaleza multifocal del CaP&#44; algunos autores sostienen que la evaluaci&#243;n de un &#250;nico n&#250;cleo de biopsia podr&#237;a no representar adecuadamente toda la carga tumoral<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">25&#44;26</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Recientemente hemos realizado una validaci&#243;n externa del SelectMDx para el diagn&#243;stico del CaP de alto grado &#40;CaPAG&#41;&#44; mostrando resultados m&#225;s modestos en comparaci&#243;n con las publicaciones originales &#40;AUC para el CaP &#8805;<span class="elsevierStyleHsp" style=""></span>Grupo de Grado<span class="elsevierStyleHsp" style=""></span>2 de 0&#44;749 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 0&#44;690-0&#44;807&#41;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;14</span></a>&#46; Tambi&#233;n hab&#237;amos evaluado el PCA3 integrado en un nomograma cl&#237;nico para detectar el CaPAG&#44; mostrando una capacidad de discriminaci&#243;n adecuada &#40;AUC&#58; 0&#44;786&#59; IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 0&#44;71-0&#44;87&#41;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a>&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Estos 86 pacientes son representativos de la poblaci&#243;n de VA en nuestro pa&#237;s&#44; ya que en un registro espa&#241;ol publicado sobre VA&#44; el 98&#37; de los hombres no recibieron una RMmp previa a la biopsia<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#46; El creciente n&#250;mero de varones candidatos a VA junto con un acceso limitado a la RMmp hace que muchos de ellos sean incluidos en la VA tras una biopsia transrectal ecodirigida de 12 n&#250;cleos&#46; Nuestros resultados muestran que la puntuaci&#243;n del SelectMDx fue casi el doble en los pacientes que experimentan PP &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#44; lo que coincide con los datos publicados anteriormente<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a>&#44; aunque con un &#237;ndice<span class="elsevierStyleHsp" style=""></span>C de Harrel modesto de 0&#44;670 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 0&#44;529-0&#44;810&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>b&#41;&#46; En nuestra opini&#243;n&#44; el SelectMDx no debe considerarse una herramienta independiente para decidir el paso a tratamiento activo&#44; aunque puede ayudar a individualizar el seguimiento seg&#250;n el riesgo de progresi&#243;n&#46; A diferencia de la RMmp&#44; el SelectMDx no requiere formaci&#243;n previa&#44; curva de aprendizaje o errores de interpretaci&#243;n&#44; lo que representa una clara ventaja&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Estos resultados destacan la importancia de obtener una puntuaci&#243;n precisa del SelectMDx en lugar de la categorizaci&#243;n del grupo de riesgo&#46; Adem&#225;s&#44; se aconseja la validaci&#243;n interna de los biomarcadores&#44; dado que el rendimiento y los valores de corte &#243;ptimos pueden diferir de las recomendaciones originales<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;30</span></a>&#46; Por ejemplo&#44; el mejor valor para la discriminaci&#243;n de PCA3 fue de 65&#44; lejos del propuesto originalmente con fines diagn&#243;sticos &#40;35&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Como era de esperar&#44; la combinaci&#243;n de un panel de dos genes con 5 variables cl&#237;nicas en un modelo como SelectMDx tiene una capacidad discriminatoria claramente superior a la de un &#250;nico biomarcador de orina como el PCA3&#44; a pesar de que la SLPP a 5<span class="elsevierStyleHsp" style=""></span>a&#241;os es similar&#58; 27&#44;97&#37; &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 14&#44;84-52&#44;74&#41; y 27&#44;57&#37; &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 16&#44;33-46&#44;54&#41;&#44; respectivamente&#46; As&#237; pues&#44; la combinaci&#243;n de biomarcadores no mejor&#243; la discriminaci&#243;n&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Nuestra investigaci&#243;n tiene algunas limitaciones&#46; A saber&#44; se trata de una cohorte retrospectiva&#44; y una minor&#237;a de pacientes se someti&#243; a una RMmp previa a la biopsia dado el periodo de inclusi&#243;n&#44; lo que podr&#237;a subestimar el valor a&#241;adido de los estudios por imagen&#46; Esto&#44; a su vez&#44; no representa el escenario actual de la VA&#44; en el que todos los pacientes reciben no solo una RMmp prebiopsia&#44; sino tambi&#233;n una RMmp de seguimiento&#44; adem&#225;s de biopsias sistem&#225;ticas y dirigidas&#46; Sin embargo&#44; pensamos que estos resultados pueden ser &#250;tiles para los centros en los que no siempre se dispone de la RMmp o cuyo rendimiento no es comparable al de los centros de gran volumen&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusiones</span><p id="par0120" class="elsevierStylePara elsevierViewall">En el contexto del CaP de bajo o muy bajo riesgo&#44; SelectMDx &#62;<span class="elsevierStyleHsp" style=""></span>5 predice la SLPP a 5<span class="elsevierStyleHsp" style=""></span>a&#241;os con una capacidad de discriminaci&#243;n moderada&#44; superando al PCA3&#46; La combinaci&#243;n de ambos no proporcion&#243; mejores resultados&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Financiaci&#243;n</span><p id="par0125" class="elsevierStylePara elsevierViewall">Este trabajo ha sido apoyado por las becas PROMETEO 2016&#47;103 de la Conselleria de Educaci&#243;n&#44; Cultura y Deporte de la Generalitat Valenciana &#40;Espa&#241;a&#41; y por la Asociaci&#243;n Contra el C&#225;ncer de Algemes&#237; &#40;Espa&#241;a&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicto de intereses</span><p id="par0130" class="elsevierStylePara elsevierViewall">MDxHealth proporcion&#243; la puntuaci&#243;n de SelectMDx para el estudio de validaci&#243;n original&#46; No se hizo ninguna contribuci&#243;n significativa al presente estudio&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introducci&#243;n y objetivos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Un porcentaje no despreciable de pacientes incluidos en programas de vigilancia activa &#40;VA&#41; para el c&#225;ncer de pr&#243;stata &#40;CaP&#41; de bajo y muy bajo riesgo son reclasificados en la biopsia confirmatoria o desarrollan progresi&#243;n de la enfermedad durante el seguimiento&#46; Nuestro objetivo es evaluar el papel del PCA3 y el SelectMDx&#44; de manera individual y combinada&#44; para predecir la progresi&#243;n patol&#243;gica &#40;PP&#41; en un programa habitual de VA&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materiales y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo y observacional que incluy&#243; 86 pacientes inscritos en un protocolo de VA desde 2009 hasta 2019&#44; con resultados de PCA3 y SelectMDx previos al diagn&#243;stico de CaP o durante su periodo de confirmaci&#243;n&#46; Se realizaron an&#225;lisis univariantes y multivariantes para la correlaci&#243;n de las puntuaciones de PCA3 y SelectMDx&#44; as&#237; como de las variables clinicopatol&#243;gicas con la supervivencia libre de progresi&#243;n patol&#243;gica &#40;SLPP&#41;&#46; Se definieron los puntos de corte m&#225;s fiables para ambos biomarcadores en el contexto de VA&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">SelectMDx mostr&#243; diferencias estad&#237;sticamente significativas en relaci&#243;n con la SLPP &#40;HR&#58; 1&#44;035&#59; IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 1&#44;012-1&#44;057&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41; con un &#237;ndice<span class="elsevierStyleHsp" style=""></span>C de 0&#44;670 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 0&#44;529-0&#44;810&#41; y un AUC de 0&#44;714 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 0&#44;603-0&#44;825&#41; a 5<span class="elsevierStyleHsp" style=""></span>a&#241;os&#46; En nuestra serie&#44; el punto de corte m&#225;s fiable para el SelectMDx fue 5&#44; con una sensibilidad y una especificidad para la PP del 69&#44;8 y del 67&#44;4&#37;&#44; respectivamente&#46; El punto de corte del test PCA3 fue de 65&#44; con una sensibilidad y una especificidad para la PP del 51&#44;16 y del 74&#44;42&#37;&#44; respectivamente&#46; La combinaci&#243;n de ambos biomarcadores no mejor&#243; la predicci&#243;n de la PP&#44; con un &#237;ndice<span class="elsevierStyleHsp" style=""></span>C de 0&#44;630 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 0&#44;455-0&#44;805&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">En el contexto del CaP de bajo o muy bajo riesgo&#44; SelectMDx &#62;<span class="elsevierStyleHsp" style=""></span>5 predijo una supervivencia libre de PP de 5<span class="elsevierStyleHsp" style=""></span>a&#241;os con una capacidad de discriminaci&#243;n moderada&#44; superando al PCA3&#46; La combinaci&#243;n de ambos no mejor&#243; los resultados&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction and objectives</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A not negligible percentage of patients included in active surveillance &#40;AS&#41; for low and very low risk prostate cancer &#40;PCa&#41; are reclassified in the confirmatory biopsy or have disease progression during follow-up&#46; Our aim is to evaluate the role of PCA3 and SelectMDx&#44; in an individual and combined way&#44; in the prediction of pathological progression &#40;PP&#41; in a standard AS program&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materials and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Prospective and observational study comprised of 86 patients enrolled in an AS program from 2009 to 2019&#44; with results for PCA3 and SelectMDx previous to PCa diagnosis or during their confirmatory period&#46; Univariate and multivariate analysis were performed to correlate PCA3 and SelectMDx scores as well as clinical and pathological variables with PP-free survival &#40;PPFS&#41;&#46; The most reliable cut-offs for both biomarkers in the context of AS were defined&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">SelectMDx showed statistically significant differences related to PPFS &#40;HR&#58; 1&#46;035&#59; 95&#37;<span class="elsevierStyleHsp" style=""></span>CI&#58; 1&#46;012-1&#46;057&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;002&#41; with a C-index of 0&#46;670 &#40;95&#37;<span class="elsevierStyleHsp" style=""></span>CI&#58; 0&#46;529-0&#46;810&#41; and AUC of 0&#46;714 &#40;95&#37;<span class="elsevierStyleHsp" style=""></span>CI&#58; 0&#46;603-0&#46;825&#41; at 5<span class="elsevierStyleHsp" style=""></span>years&#46; In our series&#44; the most reliable cut-off point for SelectMDx was 5&#44; with a sensitivity and specificity for PP of 69&#46;8&#37; and 67&#46;4&#37;&#44; respectively&#46; Same figure for PCA3 was 65&#44; with a sensitivity and specificity for PP of 51&#46;16&#37; and 74&#46;42&#37;&#44; respectively&#46; The combination of both biomarkers did not improve the prediction of PP&#44; C-index 0&#46;630 &#40;95&#37;<span class="elsevierStyleHsp" style=""></span>CI&#58; 0&#46;455-0&#46;805&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">In the context of low or very low risk PCa&#44; SelectMDx &#62;<span class="elsevierStyleHsp" style=""></span>5 predicted 5<span class="elsevierStyleHsp" style=""></span>years PP free survival with a moderate discrimination ability outperforming PCA3&#46; The combination of both tests did not improved outcomes&#46;</p></span>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;RIC&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;RIC&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Puntuaci&#243;n Gleason</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805; 3&#43;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4 &#40;4&#44;65&#37;&#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="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1 &#40;1&#44;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">N&#250;mero de n&#250;cleos obtenidos</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12&#44;16 &#40;2&#44;99&#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="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;RIC&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">N&#250;mero de n&#250;cleos positivos</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62; 1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">28 &#40;32&#44;60&#37;&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">RMmp</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No realizada&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">26 &#40;30&#44;20&#37;&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">RMmp realizada</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">18 &#40;30&#44;00&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">0&#44;823-40&#44;763&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;16 &#40;0&#44;14&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;RIC&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">PSA densidad</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&#40;basal&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#40;base line&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8&#44;052&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#44;025-32&#44;01&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2723464.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">An&#225;lisis univariante de la progresi&#243;n patol&#243;gica</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:1 [
          "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="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Progresi&#243;n patol&#243;gica antes de 5 a&#241;os</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">S&#237;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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          "es" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Progresi&#243;n patol&#243;gica a los 5 a&#241;os de seguimiento con base en nuestros puntos de corte &#243;ptimos para SelectMDx y PCA3</p>"
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Información del artículo
ISSN: 02104806
Idioma original: Español
DOI:10.1016/j.acuro.2020.10.010
Datos actualizados diariamente
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