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"apellidos" => "Hernández Fernández" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210480624000263" "doi" => "10.1016/j.acuro.2024.02.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480624000263?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578624000647?idApp=UINPBA00004N" "url" => "/21735786/0000004800000008/v1_202410021458/S2173578624000647/v1_202410021458/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "The journey of determining PD-L1 expression in muscle-invasive urothelial carcinoma" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "553" "paginaFinal" => "554" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "F. Algaba" "autores" => array:1 [ 0 => array:3 [ "nombre" => "F." "apellidos" => "Algaba" "email" => array:1 [ 0 => "falgaba@fundacio-puigvert.es" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Sección de Anatomía Patológica, Fundació Puigvert, Barcelona, Spain" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "El periplo de la determinación de la expresión de PD-L1 en el carcinoma urotelial infiltrante" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The introduction of the present-day immunotherapy in cancer has been a turning point in multiple tumors, including urothelial carcinoma. However, associated side effects and costs have prompted a continuous search for markers that can predict, as accurately as possible, a response to such therapy.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Within the complex mechanism of antigen presentation to immune cells in order to destroy neoplastic cells, the latter are protected by PD-L1 molecules and are therefore targets for immunotherapy. Hence the determination of PD-L1 expression in tumor cells and immune cells is considered a viable marker for predicting treatment response, making detection possible with anti-PD-L1 antibodies. The apparent simplicity of immunohistochemical PD-L1 testing comes up against several pitfalls when applied to invasive urothelial carcinoma. To begin with, there are several antibodies, each of which are tested using different methodologies. In addition, the threshold cutoff established to consider a positive expression is different for each antibody. Another difficulty lies in the percentage of PD-L1 expression required for each antibody to be considered positive since it varies according to drug. As the results have been updated, these percentages have changed for the same therapy as well.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Furthermore, we must add that certain immunotherapies have recently been shown to be beneficial in cases with low PD-L1 expression.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">This scenario requires recommendations regarding the response to all possible situations that may arise, both now and in the future. For this purpose, the Spanish Society of Anatomic Pathology (SEAP) gathered a group of pathologists, together with a uro-oncologist specialized in bladder tumors, to draw up a guide of recommendations based on currently available evidence.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This guide is intended to help pathologists, urologists, and oncologists by addressing certain questions that may arise when determining of PD-L1 expression, as follows:</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Which patients should be evaluated?</span><p id="par0025" class="elsevierStylePara elsevierViewall">At present, all patients with high-risk or advanced urothelial carcinoma may be susceptible to immunotherapy. However, given the rapid incorporation of indications and the overload of testing all ≥T2 category patients, it may be more appropriate to test patients at the request of the oncologist.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Which sample is best for PD-L1 determination?</span><p id="par0030" class="elsevierStylePara elsevierViewall">It must certainly be well-treated tissue from the beginning, quickly fixed in the correct amount of 10% buffered formalin, and as recent as possible from the immunohistochemical study.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The tumor must include invasive urothelial carcinoma, with the lowest number of artifacts or necrotic areas, and at least 100 tumor cells.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Membrane expression (regardless of its intensity) must be assessed in both tumor and immune cells. In cases with mixed histological subtypes, it is recommended to quantify the proportion and PD-L1 status of each of them. Tissue can come from diagnostic TUR (Transurethral Resection) or cystectomy; samples of metastases can be used (avoiding bone), but a bladder tumor not having undergone recent additional therapies is preferred.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Which antibody is best for invasive urothelial carcinoma?</span><p id="par0035" class="elsevierStylePara elsevierViewall">Multiple studies have shown interchangeable performance of almost all antibodies with the least equivalent being SP142.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Depending on the antibody, the staining platform will be DAKO or Ventana.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">What to do if a first determination is negative?</span><p id="par0040" class="elsevierStylePara elsevierViewall">If the methodology has been carried out correctly, no further search for PD-L1 in another sample is indicated.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">How should results be reported?</span><p id="par0045" class="elsevierStylePara elsevierViewall">This is one of the most important aspects. The information must not only be clear and complete, but should also be applicable to different immunotherapy treatments, which may require different percentages of PD-L1 expression.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Thus, reports should include data on the sample and the methodology followed (antibody and platform used and the positive and negative controls performed). Regarding the reporting of PD-L1 expression, it is most practical to indicate the percentage of positive neoplastic and immune cells so that the oncologist can consider positive or negative PD-L1 expression according to the type of immunotherapy to be used. If considered appropriate, the CPS (Combined Positive Score: positive neoplastic cells plus positive immune cells divided by the number of viable tumor cells, multiplied by 100, so that the result is a number, not a percentage) can also be indicated.</p><p id="par0055" class="elsevierStylePara elsevierViewall">With these indications, we have tried to homogenize the results between different pathology departments and ensure that the information provided can be applied to all types of immunotherapy.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Which patients should be evaluated?" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Which sample is best for PD-L1 determination?" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Which antibody is best for invasive urothelial carcinoma?" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "What to do if a first determination is negative?" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "How should results be reported?" ] 5 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. 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Journal Information
Vol. 48. Issue 8.
Pages 553-554 (October 2024)
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Vol. 48. Issue 8.
Pages 553-554 (October 2024)
Editorial
The journey of determining PD-L1 expression in muscle-invasive urothelial carcinoma
El periplo de la determinación de la expresión de PD-L1 en el carcinoma urotelial infiltrante
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F. Algaba
Sección de Anatomía Patológica, Fundació Puigvert, Barcelona, Spain
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