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array:23 [ "pii" => "S217357862030158X" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2020.12.006" "estado" => "S300" "fechaPublicacion" => "2021-01-01" "aid" => "1311" "copyright" => "AEU" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Actas Urol Esp. 2021;45:1-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0210480620301972" "issn" => "02104806" "doi" => "10.1016/j.acuro.2020.09.002" "estado" => "S300" "fechaPublicacion" => "2021-01-01" "aid" => "1311" "copyright" => "AEU" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Actas Urol Esp. 2021;45:1-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artículo de revisión</span>" "titulo" => "Actualización y optimización de la vigilancia activa en cáncer de próstata en 2021" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "1" "paginaFinal" => "7" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Update and optimization of active surveillance in prostate cancer in 2021" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Rubio-Briones, B. Pastor Navarro, L.M. Esteban Escaño, A. Borque Fernando" "autores" => array:4 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Rubio-Briones" ] 1 => array:2 [ "nombre" => "B." "apellidos" => "Pastor Navarro" ] 2 => array:2 [ "nombre" => "L.M." "apellidos" => "Esteban Escaño" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Borque Fernando" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S217357862030158X" "doi" => "10.1016/j.acuroe.2020.12.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217357862030158X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480620301972?idApp=UINPBA00004N" "url" => "/02104806/0000004500000001/v1_202101030653/S0210480620301972/v1_202101030653/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173578620301566" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2020.08.010" "estado" => "S300" "fechaPublicacion" => "2021-01-01" "aid" => "1308" "copyright" => "AEU" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Actas Urol Esp. 2021;45:8-20" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Genetic counseling in prostate cancer: How to implement it in daily clinical practice?" 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July 2020).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Borque-Fernando, R. Espílez, D. Miramar, D. Corbatón, A. Rodríguez, E. Castro, J. Mateo, L. Rello, A. Méndez, M.J. Gil Sanz" "autores" => array:10 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Borque-Fernando" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Espílez" ] 2 => array:2 [ "nombre" => "D." "apellidos" => "Miramar" ] 3 => array:2 [ "nombre" => "D." "apellidos" => "Corbatón" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Rodríguez" ] 5 => array:2 [ "nombre" => "E." "apellidos" => "Castro" ] 6 => array:2 [ "nombre" => "J." "apellidos" => "Mateo" ] 7 => array:2 [ "nombre" => "L." "apellidos" => "Rello" ] 8 => array:2 [ "nombre" => "A." "apellidos" => "Méndez" ] 9 => array:2 [ "nombre" => "M.J." "apellidos" => "Gil Sanz" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210480620301947" "doi" => "10.1016/j.acuro.2020.08.009" "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/S0210480620301947?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578620301566?idApp=UINPBA00004N" "url" => "/21735786/0000004500000001/v1_202101060759/S2173578620301566/v1_202101060759/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Update and optimization of active surveillance in prostate cancer in 2021" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "1" "paginaFinal" => "7" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "J. Rubio-Briones, B. Pastor Navarro, L.M. Esteban Escaño, A. Borque Fernando" "autores" => array:4 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Rubio-Briones" "email" => array:1 [ 0 => "jrubio@fivo.org" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "B." "apellidos" => "Pastor Navarro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "L.M." "apellidos" => "Esteban Escaño" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "A." "apellidos" => "Borque Fernando" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Urología, Instituto Valenciano de Oncología, Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Laboratorio de Biología Molecular, Instituto Valenciano de Oncología, Valencia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Estadística, Universidad de Zaragoza, Zaragoza, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio Urología, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Actualización y optimización de la vigilancia activa en cáncer de próstata en 2021" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Context and objective</span><p id="par0005" class="elsevierStylePara elsevierViewall">After the results of the long-term observation of the SPCG-4<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and PIVOT<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> studies, and 10 years after the active monitoring of PROTECT<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and the results of the longest series of active surveillance (AS), it is prescriptive to highlight that a patient with low-risk prostate cancer (PCa) must be thoroughly informed of the possibility of a non-active strategy, which will differ between observation or AS depending on the age and comorbidities of the patient. The opposite, then, suggests malpractice. At 15 years of follow-up, the cumulative risk of death from low-risk PCa without any treatment was 8.9% (95% CI: 7.4–10.5), compared to 49.5% (95% CI: 95%: 46.5–52.4) for other causes, while in patients treated with curative intent in the same group it was 5.1% (95% CI: 2.5–8.9),<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> which leaves little “profit margin” for active treatments and a lot for a good AS program.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Therefore, in this chapter we assume AS to be a mandatory strategy in the management of PCa, and responsibility for the Registro Español en Vigilancia Activa (<span class="elsevierStyleItalic">Spanish Registry of Active Surveillance</span>) PIEM/AEU/2014/0001 (<a href="http://www.piem.aeu.es;">www.piem.aeu.es;</a> NCT02865330). In a narrative review with more than 3200 patients followed in AS,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> we will unfold the aspects that in 2021 may be controversial in their current application.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">How can we optimize selection criteria?</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Good use of conventional criteria</span><p id="par0015" class="elsevierStylePara elsevierViewall">The recommendations that the EAU Clinical Guidelines grant to AS have not changed substantially in their updates during the last years, which is based on standard transrectal biopsy (Bx) of 10–12 cylinders (TRUSx12) where basically patients with an expectation of life greater than 10 years, cT1c-cT2, PSA<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>10/ml, Gleason<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>3, ≤2 affected cylinders with a percentage of affectation of each cylinder<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>50% are considered good candidates for AS with a strong grade of recommendation. A consensus of experts also establishes that in initial diagnoses from a mapping Bx plus Bx directed to PIRADs 3–5 lesions, the affected areas are considered instead of the number of positive cylinders. In addition, only one positive cylinder per zone of targeted Bx is considered, otherwise AS would not be offered to many candidates because of “adding” positive cylinders from the same zone.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The calculation of prostate volume using multiparametric magnetic resonance imaging (mpMRI) confers even more importance to PSA density (PSAD), which has already been pointed out in multiple studies<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> as an independent variable for the prediction of pathologic progression in AS when it was calculated by ultrasound. The opportunity of PSAD was also endorsed by the study of RP specimens in candidates for AS from Johns Hopkins, which, together with GG2, were the predictive variables of unfavorable anatomical pathology specimens.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Take advantage of and collaborate with uropathologists</span><p id="par0025" class="elsevierStylePara elsevierViewall">The pathologist must be tested against expert uropathologists to optimize their ability to grade, adopting the recommendations made by the ISUP.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> All the groups that are included in the Movember GAP3 have done so in order to observe 89% agreement between central pathologists and the reference, where in addition an incidence of 3.6% of cribriform or intraductal pattern was detected in the included Bx, which currently should not be included in AS. A recent review shows that these patterns can appear in 2% of low-risk PCa and up to 23% of intermediate-risk.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Gleason 4 must also be quantified as a percentage, since it is accepted to include among the candidates for AS those in the intermediate favorable group with less than 10% Gleason 4, explaining to the patient that this entails a slightly higher risk of metastasis to follow-up<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>10 years.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,11</span></a> With the recent recommendations of the ISUP to differentiate Gleason 7 in 3<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>4 (GG2) from 4<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>3 (GG3), adapted risk classifications have been proposed (the prognostic groups of the University of Cambridge) which allow for a greater inclusion of patients in AS by determining the progression from GG1–2 to GG3 as the fundamental event for determining active treatment in AS.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Compute genetic and molecular characteristics and the heterogenicity of PCa</span><p id="par0030" class="elsevierStylePara elsevierViewall">We are living through an exciting initial phase of the genetic and molecular characterization of different PCa phenotypes. At present, patients with BRCA1/2 mutations or other genetic alterations of DNA repair genes should already be ruled out for AS due to their worse evolutionary behavior.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Different serum and urinary biomarkers have been proposed for the best selection of patients, but always in retrospective series and adapting their possibilities to the strictly diagnostic setting, so that they are not routinely used in the management of AS.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> However, tissue gene panels have been proposed for optimizing the selection of AS candidates in prostate Bx. The most specifically designed for this has been the Genomic Prostate Score (Oncotype), retro and prospectively related<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> to the presence of unfavorable pathological anatomy (GG<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>3 and/or pT<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>3 and/or pN+) in RP specimen, with the development of metastasis (M+) or CSM (cancer-specific mortality). In AS series it has been related to the risk of pathologic progression in follow-up Bx in AS.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Its use is recommended for borderline cases, such as high-burden GG1 or with PSAD<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.15 or low-burden GG2, with the contrast that there are molecular studies that question the reproducibility of a single Bx cylinder due to the multiclonality of PCa.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">mpMRI in the confirmation period</span><p id="par0040" class="elsevierStylePara elsevierViewall">mpMRI is not used in a routine or reproducible way in many centers.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Thus, extrapolating the results that are given in the literature, coming from selected academic centers and with highly trained radiologists, is certainly dangerous without a prior training program and auditing the results of the mpMRI and the Bx in each center.</p><p id="par0045" class="elsevierStylePara elsevierViewall">If the patient was diagnosed by a TRUSx12, it is mandatory to perform a confirmatory Bx. Clinical Guidelines recommend that mpMRI be carried out prior to this if it has not been done before diagnostic Bx (level of evidence IA). When a lesion<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>PIRADs-3 is seen, guided Bx with mapping Bx must be added to the confirmatory Bx aiming to maximize the information derived from the confirmatory Bx and include the patient in the AS program definitely with the best of the collaterals, bypassing the mapping Bx that 10–15% of significant PCa that the mpMRI does not detect, such as the cribriform pattern. The presence of a PIRADs 4–5 in the initial mpMRI is recognized as a predictive factor of progression, and in any case the technical characteristics and the machine of the initial one will allow a comparative study that can optimize follow-up.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Initial Bx optimization</span><p id="par0050" class="elsevierStylePara elsevierViewall">The debate between the transrectal (TR) or transperineal (TP) route extends beyond this chapter. It is advisable to have both and decide which may be the most appropriate based on the size of the prostate, the location of the suspicious lesion and the characteristics of the patient. It seems plausible that a zonal mapping of the entire prostate<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2–4<span class="elsevierStyleHsp" style=""></span>Bx targeting the most suspicious lesion through the TP route would be the strategy of choice in the confirmation period. This is due to the possibility of making a very reliable mapping adapted to the prostate volume and with better tolerability by the patient.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Controversial indications for active surveillance</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Active surveillance in <60 years</span><p id="par0055" class="elsevierStylePara elsevierViewall">There is reluctance on the part of Urology to include a young patient with a 10–15-year life expectancy in AS. In part this is logical as the data from the AS series do not exceed that time. The data at 23 years of the SPCG-41 favorable to RP are also not comparable to those of the current low-risk group classified after the ISUP 2005 modifications, since the low-risk data of that study are comparable to those of the intermediate group with up-to-date clinical and anatomopathological criteria.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> However, in the Movember GAP-3 group, we observed that the percentage of AS dropouts at 5 years in <60 years was 38%, compared to 43% in patients between 60 and 70 years, and that RP according to these age ranges offered rates of unfavorable pathological anatomy in 21% and 29%, respectively.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> For decades, young patients have had a 13–17% lower risk of increased grade in AS and 12–20% of pathologic progression.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> It is about gaining years of quality of life in AS and rescuing according to risk when progression is detected.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Active surveillance in GG2 (Gleason 3<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>4)</span><p id="par0060" class="elsevierStylePara elsevierViewall">In the Movember GAP-3 we have observed that only 13% of the patients were included with GG2 (2.6% in AEU/PIEM/2014/0001), and that their abandonment rate was greater at 5 and 10 years of follow-up, compared to those included as GG1. However, of those who underwent RP, it was observed that the rates of adverse PA were similar in both groups. It is obvious that including a patient with GG2 in AS carries a risk of biochemical progression (BP) after active treatment. For example, within the Swedish ERPCS group, it was observed that said rate in those included in AS of the intermediate group had a HR of BP of 3.5 compared to those included with very low risk.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Additionally, within the Klotz series, with a mean follow-up of 6.3 years and an incidence of metastasis (M+) of 3.1% in 980 patients, it is established that inclusion with Gleason 7 is an independent variable of progression M + in the regression analysis.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Nevertheless, it is becoming more and more generalized that the important objective to avoid in AS is the progression to unfavorable PA, understanding this as pT3 and/or pN+ and/or GG3. Patients included in AS at UCSF with CAPRA 3–5 with only one Gleason 4 cylinder had the same behavior as those included with Gleason 3<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>3. However, those included with more than one Gleason 4 cylinder did have higher BP rates after RP when adjusting for PSAD and age.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24,25</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">As a corollary, it is currently accepted that AS is a good strategy for patients in the intermediate group for whom there is no other second variable that could confer an independent and therefore summative risk, namely: patients defined as an intermediate group for having PSA 10–20/ml (particularly if the PSAD is <0.15), GG2 with 5–10% Gleason 4, especially if the mpMRI does not show a PIRADs 4–5, and if a tissue marker such as GPS signals a low risk of unfavorable PA.</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Can we decrease abandonment rates by optimizing follow-up?</span><p id="par0070" class="elsevierStylePara elsevierViewall">Many authors already advocate differentiated follow-ups according to risk of progression. The presence of a confirmatory Bx without tumor is a favorable prognostic factor for not having further progression.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Considering the number of positive cylinders between both Bx, diagnostic and confirmatory, in groups of 1, 2, 3 or 4 positives they signal progression-free survival rate curves in Bx of clearly differentiated follow-up.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Regarding parameters derived from PSA kinetics, none clearly predicts progression in Bx or RP. In a study of a large cohort of patients in AS, a PSADT <33 years or a PSAV of >2<span class="elsevierStyleHsp" style=""></span>ng/ml/year was detected in 50% of patients who did not progress or require treatment, highlighting the lack of sensitivity of these parameters.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Nevertheless, they are usually used to induce an additional Bx in the face of aggressive kinetics. Currently there are several online calculators that include PSA kinetic variables proposing personalized follow-ups (<a href="https://sunnybrook.ca/content/?page=asure-aboutapp">https://sunnybrook.ca/content/?page=asure-aboutapp</a>, <a href="https://emcbiostatistics.shinyapps.io/prias_biopsy_recommender">https://emcbiostatistics.shinyapps.io/prias_biopsy_recommender</a>). These are potentially attractive, but our advice is to find out know how they have been built and to demand external validation of them. Even so, it would be mandatory for all these tools, which are so easy to use on the web, to be individually validated in each center before their routine application.</p><p id="par0080" class="elsevierStylePara elsevierViewall">In addition, prognosis worsens if the patient does not comply with the follow-up protocols, including the Bx when these are protocolized or induced by some cause. In centers of excellence, it is proposed that mpMRI should replace Bx in follow-up.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> The different interpretation of the mpMRI NPV due to its dependence on the prevalence of the disease, its lack of standardization and interpretation, and the fact that 15% of clinically significant tumors are not seen by mpMRI mean that, for the moment, the Guidelines do not consider ignoring the follow-up Bx. Similarly, no other serum, urinary or tissue biomarker has consistently and reproducibly demonstrated that individually it is a useful tool for predicting tumor progression at the initial time of inclusion in AS or in the confirmation period. Furthermore, the use of biomarkers should demonstrate an improvement in the patient's oncological prognosis, and as of now neither this nor its cost effectiveness in AS has been demonstrated.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Another controversial issue is to recognize that exclusive progression in volume while maintaining the GG1 is relevant to moving on to active treatment. The indication of RP by exclusive progression in volume of affected cylinders in the PRIAS group was not related to an unfavorable PA in specimen, unlike when it was done by progression in Bx to Gleason 7 or by progression to cT3.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> In the Spanish AS registry—AEU/PIEM/2014/0001 (NCT02865330) – the indication for this progression criterion did not differ in the rates of unfavorable PA from those RP that were indicated by anxiety of the patient/urologist.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Although the significance of the exclusive progression in volume in follow-up Bx will have to be defined by the post-RP BP rate differentiated by each of the progression criteria. It is evident that exclusive progression in AS to a high tumor volume of GG1, which we know leads to 30% overstaging and overgradading in RP specimens in classic series, is a field where the investigation of new biomarkers and the technical refinement of mpMRI and other imaging techniques have opened doors to research, given that those series did not have such an optimized diagnosis as the patients currently included in AS.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Another point to protocolize in an AS program is when to move from AS to observation. Although most protocols contemplate it at 80 years of age, it is evident that the occurrence of clinical events and comorbidities should rationalize follow-up and consider this possibility if they shorten life expectancy.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> This fact has been found to occur 10 years after the onset of AS in 10% of those who started it healthy at 55 years and in 50% of those who started it at 70. For this reason, these are indicative figures that should be reported to all patients at the beginning of the AS program.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Results of active surveillance</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Quality of life</span><p id="par0095" class="elsevierStylePara elsevierViewall">The reason for putting quality of life (QoL) before cancer outcomes is that this is itself the raison d’être of AS. It must not be forgotten that, in addition, the QoL that the patient experiences in AS depends mainly on the trust that the patient has in his doctor. This has been shown in a survey of patients in which they view trust in their doctors in the AS strategy is the most important factor in their decision to accept inclusion in AS.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> In the PROTECT study, QoL was clearly better in the active monitoring arm.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Obviously, a cancerphobic, anxious, or noncompliant patient is not a good candidate for AS. The variables that independently predict a poor quality of life for a patient in AS are the absence of a partner, an altered mental state at the beginning, the absence of opinion from more than one doctor, especially when the patient receives contradictory opinions, an initial Bx of less than 18 cylinders and a time between the diagnosis of PCa and entry into AS of less than 5 months.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">That said, it is important to note that in the largest international series of patients in AS, the Movember GAP-3, 12.8% of patients leave AS at 5 years without having demonstrated pathologic progression.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Therefore, it is obvious that, as Marañón used to say, “the best cure is the word”. That principle should accompany us as therapists throughout the time that the patient remains on AS.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Oncological results</span><p id="par0110" class="elsevierStylePara elsevierViewall">As always, we must first review the results obtained from prospective studies due to their greater robustness, and only the PROTECT study does not offer differences at 10 years in overall and cancer-specific survival, although it does have a higher rate of M+ in the branch of active monitoring (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>33; 6.3 events/1000 person-years; 95% CI: 4.5–8.8) vs in the RP branch (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>13; 2.4 events/1000 person-years; 95% CI: 1.4–4.2) or in radiotherapy (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>16; 3 events/1000 person-years; 95% CI 1.9–4.9) (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.004). However, it should be noted that the active monitoring branch does not offer mpMRI or Bx during the initial characterization or during follow-up, nor does it specify the number of positive cylinders at the beginning. It included 20% of Gleason 7 and the 2% Gleason 8 and proposed active treatment by PSA kinetics. Hence it is obvious that all these characteristics invalidate it as a comparator to a modern AS program.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Therefore, we must take into account the fact that AS results are published based on those of the reference series. They are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, adding our own experience as a national comparator.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">In the IVO series, of 540 patients with a median follow-up of 52 months, 32 died from other causes, none from PCa, and 5 developed metastases (the 5 included without strictly meeting the inclusion criteria). The pathological progression-free survival at 5 and 10 years was 56 and 47% of the cases.</p><p id="par0125" class="elsevierStylePara elsevierViewall">The series by Dr. L. Klotz is a reference point in terms of the number of patients in the single-center series (993) and the longest follow-up time.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> The actuarial CSS at 10, 15, and 20 years was 97.9, 93.5, and 86.3%, respectively. The overall rate of metastasis was 2.8%, diagnosed at a median of 9.6 years. Active treatment-free survival at 15 years was 52.3% and remained the same at 20 years. Of the 208 patients treated, 44 (21%) or 5% of the overall cohort suffered BP, 11% in those treated with RP and 22% in those treated with radiotherapy. The cumulative rate of death from other causes and from PCa gave a ratio of 9.7: 1 during the follow-up of their series.</p><p id="par0130" class="elsevierStylePara elsevierViewall">One final consideration of the results must be that they are all based on Gleason score scales prior to the recommendation of the ISUP in 2005,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> which, as is known, tended to consider a significant percentage of old Gleason 3<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>3 as Gleason 3<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>4, including all cribriform patterns that are currently a contraindication for AS. Currently, Gleason 3<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>3 has a better prognosis due to the optimization of its determination,<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> also knowing that in patients with cT1c and PSA 4–10 the proportion of GG1 falls from 82% in 1998 to 40% in 2012 after applying ISUP 2005.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Thus, logically enough it is to be expected that the results of the patients that we put into AS today will be, if possible, even better than those published at the moment,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> especially if we add to this irrefutable fact the current characterization by MRI and better techniques for initial and follow-up Bx.</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Do we rescue in time when we detect progression?</span><p id="par0135" class="elsevierStylePara elsevierViewall">The median time to rescue depends a lot on the follow-up schemes. For example, in our center, the RPs derived from the AS program have a median time of completion of 11 months after the diagnosis of PCa. In the case of very low, low or intermediate risk PCa, it seems a reasonable time and therefore not important. At 6 years of mean follow-up of the patients included in AS from the Swedish arm of the ERSPC after different rescue treatments applied to progression in AS, BP rates were observed at 5, 10 and 14 years of 6.7, 13, 6 and 30.2%, respectively.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In IVO, the biochemical progression-free survival (bPFS) at 5 years of the 209 cases in AS that switched to any active treatment is 89.6% (95% CI: 85.02–94.55%), which does not differ substantially from the percentages of bPFS of patients with inclusion criteria in AS who were treated with RP (85.04%) or initial brachytherapy in our center (85.87%).</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0140" class="elsevierStylePara elsevierViewall">The involvement of urologists in charge of AS, pathologists and radiologists in implementing all the improvements that the last decade has provided, undoubtedly allows for better selection and individualized follow-up. We hope that this will result in better quality of life and oncological outcomes of the patients we currently include in AS.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1445105" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1318527" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1445106" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1318526" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Context and objective" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "How can we optimize selection criteria?" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Good use of conventional criteria" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Take advantage of and collaborate with uropathologists" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Compute genetic and molecular characteristics and the heterogenicity of PCa" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "mpMRI in the confirmation period" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Initial Bx optimization" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Controversial indications for active surveillance" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Active surveillance in <60 years" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Active surveillance in GG2 (Gleason 3 + 4)" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Can we decrease abandonment rates by optimizing follow-up?" ] 8 => array:3 [ "identificador" => "sec0060" "titulo" => "Results of active surveillance" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Quality of life" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Oncological results" ] ] ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Do we rescue in time when we detect progression?" ] 10 => array:2 [ "identificador" => "sec0080" "titulo" => "Conclusions" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-08-20" "fechaAceptado" => "2020-09-06" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1318527" "palabras" => array:5 [ 0 => "Active surveillance" 1 => "Prostate cancer" 2 => "Low risk" 3 => "Multiparametric magnetic resonance" 4 => "PSAd" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1318526" "palabras" => array:5 [ 0 => "Vigilancia activa" 1 => "Cáncer de próstata" 2 => "Bajo riesgo" 3 => "Resonancia magnética multiparamétrica" 4 => "PSAd" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Within the paradigm shift of the last decade in the management of prostate cancer (PCa), perhaps the most relevant event has been the emergence of active surveillance (AS) as a mandatory strategy in low-risk disease. We carry out a critical review of the clinical, pathological and radiological improvements that allow optimizing AS in 2021.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Critical narrative review of the literature on improvement issues and controversial aspects of AS.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Adequate use of traditional criteria, optimized by enhanced biopsy and calculation of the prostate volume technique thanks to multiparametric magnetic resonance imaging (mpMRI) allow a better selection of patients for AS. This management should not be limited to patients under 60 years of age, and patients with intermediate-risk PCa should be carefully selected to be included. Biopsies are still required in the follow-up, which can be personalized according to risk patterns. The pathologist must identify the cribriform or intraductal histology on biopsies in order to exclude these patients from AS, in the same way as with patients with alterations in DNA repair genes.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Controversial indications such as the inclusion of patients from intermediate-risk groups, or the transition to active treatment due to exclusive progression in tumor volume, should be further optimized. It is possible that the future competition of tissue biomarkers, the refinement of objective parameters of mpMRI and the validation of PSA kinetics calculators may sub-stratify risk groups.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción y objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Dentro del cambio de paradigma de la última década en el manejo del cáncer de próstata (CaP), quizás el hecho más relevante haya sido la irrupción de la vigilancia activa (VA) como estrategia obligada en el de bajo riesgo. Realizamos una revisión crítica de las mejoras clínicas, anatomopatológicas y radiológicas que permiten optimizar la VA en 2021.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Revisión crítica narrativa de la literatura en los temas de mejora y en los aspectos controvertidos de la VA.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">El buen uso de los criterios clásicos, optimizados por una mejor técnica de biopsia y cálculo del volumen prostático gracias a la resonancia magnética multiparamétrica (RMmp), permite una mejor selección de pacientes para VA. No se debe restringir la VA en menores de 60 años y se debe seleccionar qué pacientes con CaP de riesgo intermedio pueden incluirse en VA. Las biopsias siguen siendo necesarias en el seguimiento, pero este se puede individualizar según patrones de riesgo. El patólogo ha de reseñar el patrón cribiforme o intraductal en las biopsias para no ser incluidos en VA, al igual que los pacientes con alteraciones en los genes de reparación del ADN.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Se debe seguir optimizando las indicaciones controvertidas, como la inclusión de pacientes de grupo intermedio o el paso a tratamiento activo por progresión exclusiva en volumen tumoral. Es posible que el concurso futuro de biomarcadores tisulares, el refinamiento de parámetros objetivos de la RMmp y la validación de calculadoras cinéticas del PSA puedan subestratificar grupos de riesgo.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "⋆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Rubio-Briones J, Pastor Navarro B, Esteban Escaño LM, Borque Fernando A. Actualización y optimización de la vigilancia activa en cáncer de próstata en 2021. Actas Urol Esp. 2021;45:1–7.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">IVO: Instituto Valenciano de Oncología; M+: metastasis; OCM: other-cause mortality; RP: radical prostatectomy; CSS: cancer-specific survival; OS: overall survival.</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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author, center/study and year \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 \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span> \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 \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Median follow-up (m) \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 \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">pT3 in derived RP \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 \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OS at 10 years \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 \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CSS at 10 years \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Van AS, 2008 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">326 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8/18 (44%) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">98% \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \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">Carter, 2007 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">407 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10/49 (20%) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">98% \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \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">Adamy, 2011 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1000 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4/24 (17%) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90% \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99% \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">Rubio-Briones (IVO), 2018 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">540 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21.1% \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89% \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \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">Roemeling, 2008 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">278 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89% \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \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">Khatami, 2007 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">270 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \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">Klotz (U. Toronto), 2015 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">993 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85% \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">97.9% \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">Tosoian (Cl. Mayo), 2015 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.298 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93% \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99.9% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2485375.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Oncological results of active surveillance.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:37 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Radical prostatectomy or watchful waiting in prostate cancer — 29-year follow-up" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. 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