Magnetic resonance as imaging diagnostic tool in prostate cancer: New evidences-The EAU section of uro-technology position | Actas Urológicas Españolas (English Edition)

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Álvarez-Maestro, J. Gómez Rivas, J. Quesada Olarte, D.M. Carrión, C. Trelles Guzman, C. Ballesteros, L.M. Quintana, A. Aguilera Bazán, L. Martínez-Piñeiro, E. Liatsikos, E. Barret" "autores" => array:11 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Álvarez-Maestro" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Gómez Rivas" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Quesada Olarte" ] 3 => array:2 [ "nombre" => "D.M." "apellidos" => "Carrión" ] 4 => array:2 [ "nombre" => "C." "apellidos" => "Trelles Guzman" ] 5 => array:2 [ "nombre" => "C." "apellidos" => "Ballesteros" ] 6 => array:2 [ "nombre" => "L.M." "apellidos" => "Quintana" ] 7 => array:2 [ "nombre" => "A." "apellidos" => "Aguilera Bazán" ] 8 => array:2 [ "nombre" => "L." "apellidos" => "Martínez-Piñeiro" ] 9 => array:2 [ "nombre" => "E." "apellidos" => "Liatsikos" ] 10 => array:2 [ "nombre" => "E." 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"apellidos" => "Rodriguez-Antolin" ] 6 => array:1 [ "colaborador" => "On behalf of Grupo Español de Cáncer de Próstata (GESCAP)" ] 7 => array:1 [ "colaborador" => "On behalf of Grupo Español de Cáncer de Próstata (GESCAP)" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210480619301433" "doi" => "10.1016/j.acuro.2019.06.006" "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/S0210480619301433?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578620300214?idApp=UINPBA00004N" "url" => "/21735786/0000004400000003/v1_202004300403/S2173578620300214/v1_202004300403/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173578620300159" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2019.08.009" "estado" => "S300" "fechaPublicacion" => "2020-04-01" "aid" => "1204" "copyright" => "AEU" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Actas Urol Esp. 2020;44:139-47" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Liquid biopsy and prostate cancer. 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Puche-Sanz, A. Rodríguez-Martínez, M.C. Garrido-Navas, I. Robles-Fernández, F. Vázquez-Alonso, M.J. Álvarez Cubero, J.A. Lorente-Acosta, M.J. Serrano-Fernández, J.M. Cózar-Olmo" "autores" => array:9 [ 0 => array:2 [ "nombre" => "I." "apellidos" => "Puche-Sanz" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Rodríguez-Martínez" ] 2 => array:2 [ "nombre" => "M.C." "apellidos" => "Garrido-Navas" ] 3 => array:2 [ "nombre" => "I." "apellidos" => "Robles-Fernández" ] 4 => array:2 [ "nombre" => "F." "apellidos" => "Vázquez-Alonso" ] 5 => array:2 [ "nombre" => "M.J." "apellidos" => "Álvarez Cubero" ] 6 => array:2 [ "nombre" => "J.A." "apellidos" => "Lorente-Acosta" ] 7 => array:2 [ "nombre" => "M.J." "apellidos" => "Serrano-Fernández" ] 8 => array:2 [ "nombre" => "J.M." 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Álvarez-Maestro, J. Gómez Rivas, J. Quesada Olarte, D. Carrión Monsalve, C. Trelles Guzman, C. Ballesteros, L.M. Quintana, A. Aguilera Bazán, L. Martínez-Piñeiro, E. Liatsikos, E. Barret" "autores" => array:11 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Álvarez-Maestro" "email" => array:1 [ 0 => "malvarezmaestro@hotmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Gómez Rivas" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Quesada Olarte" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "D." "apellidos" => "Carrión Monsalve" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "C." "apellidos" => "Trelles Guzman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "C." "apellidos" => "Ballesteros" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "L.M." "apellidos" => "Quintana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "A." "apellidos" => "Aguilera Bazán" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 8 => array:3 [ "nombre" => "L." "apellidos" => "Martínez-Piñeiro" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 9 => array:3 [ "nombre" => "E." "apellidos" => "Liatsikos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 10 => array:3 [ "nombre" => "E." "apellidos" => "Barret" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Departamento de Urología, Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto de Investigación, Hospital Universitario La Paz (IdiPAZ), Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Urología, Universidad de Patras, Patras, Grecia" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Departamento de Urologia, Instituto Mutualista Montsouris, Paris, France" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La resonancia magnética como herramienta para el diagnóstico del cáncer de próstata: nuevas evidencias y posicionamiento de la ESUT (EAU Section of Uro-Technology)" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 675 "Ancho" => 1667 "Tamanyo" => 72805 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "The use of multiparametric MRI (mpMRI) as a triage test enables all men with negative mpMRI to be spared from receiving a biopsy, opting for a surveillance strategy mainly based on the use of PSA and follow- up mpMRI. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article)." ] ] ] "textoCompleto" => "IntroductionIn recent years, evidence has accrued to support the introduction of multiparametric magnetic resonance imaging (mpMRI) in the prostate cancer (PCa) diagnostic pathway. The exact role of mpMRI in different settings is not widely agreed. In this review, we look at the use of MRI in the prostate cancer diagnostic. Prostate cancer is the most commonly diagnosed solid-organ malignancy amongst men in the USA. The current diagnostic pathway for PCa is based on the use of prostatic specific antigen (PSA) and digital rectal examination (DRE) to inform the decision to undertake systematic transrectal ultrasound-guided biopsy (TRUSBx). Despite recommendations to the contrary, men still most commonly present to clinicians for evaluation following an elevated prostate specific antigen (PSA) test. PSA has poor specificity for aggressive cancer. This diagnostic pathway has led, over the years, to an increase in PCa incidence and a slight reduction in cancer-specific mortality.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Overdiagnosis and overtreatment of indolent prostate cancer represent important drawbacks of this approach, that have not been adequately addressed by the use of active surveillance for men with low risk disease.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> In an attempt to curb these latter two issues there have been extensive efforts to improve patient selection. The use of biomarkers such as PHI, 4Kscore, and SelectMDx has demonstrated the potential to aid risk stratification of patients, but these are not yet widely adopted in routine clinical practice and the latter two have not received USA Food and Drug Administration clearance to date.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Similarly, risk calculators have also been used as a risk-stratification tool to improve patient selection.The typical sampling strategy is a 10–12 core TRUS biopsy with cores directed principally at the base, midgland and apex of the peripheral zone of each of the left and right lobes of the prostate. The use of anteriorly directed cores is not recommended at first biopsy, according to the most recent European Association of Urology guidelines 2019.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Ten to twelve core biopsies are recommended in larger prostates, with > twelve cores not being significantly more conclusive. Ultrasound (US)-guided biopsy is now the standard of care. Prostate biopsy is performed by either the transrectal or transperineal approach.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Some evidence suggests reduced infection risk with the transperineal route. Sextant biopsy is no longer considered adequate.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Grey-scale TRUS is not reliable at detecting PCa.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Thus, there is no evidence that US-targeted biopsies can replace systematic biopsies. New sonographic modalities such as sonoelastography and contrast-enhanced US are still under investigation and not ready for routine use. Although this biopsy strategy is superior to the initial “random systematic” 6-core TRUS-Bx, as reported by Stamey and Hodge, a meta-analysis that investigated the comparison between 12-core TRUS-Bx and whole gland radical prostatectomy specimens, found false negative rates for TRUS-Bx of up to 49%.<a class="elsevierStyleCrossRefs" href="#bib0030">6,7</a>In addition to biomarkers and risk calculators, there has been considerable progress in the landscape of prostate imaging. Multiparametric magnetic resonance imaging (mpMRI) has come to the forefront of local tumor imaging over the last decade. This has most commonly been used in the setting of previous negative TRUSB, but the observed utility has prompted clinicians to also adopt it in primary diagnostic pathway.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> In keeping with this, the evidence for the use of mpMRI is primarily for the population of men with a previous negative TRUSB. There is growing interest in the use of mpMRI of the prostate to refine the diagnostic pathway of PCa, improve risk stratification, and diagnose only those men who could benefit from active treatment. Prostate MRI was initially introduced in late 1980s as an imaging technique for local staging of PCa, identifying extracapsular extension and seminal vesicle invasion.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Despite the promising role of mpMRI in the diagnostic pathway of PCa, international panels of experts are cautious in advising the use of MRI and subsequent MRI-TBx in every setting of PCa diagnosis. In particular there is much debate about the need for systematic cores in men having MRI-targeted biopsies, and in those men with a negative MRI.Recommendations international guidelinesThe UK NICE Guidelines 2019 recommends:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-Do not routinely offer multiparametric MRI to people with prostate cancer who are not going to be able to have radical treatment.</li><li class="elsevierStyleListItem" id="lsti0010">-Offer multiparametric MRI as the first-line investigation for people with suspected clinically localized prostate cancer. Report the results using a 5‑point Likert scale.</li><li class="elsevierStyleListItem" id="lsti0015">-Offer multiparametric MRI-influenced prostate biopsy to people whose Likert score is 3 or more.</li><li class="elsevierStyleListItem" id="lsti0020">-Consider omitting a prostate biopsy for people whose multiparametric MRI Likert score is 1 or 2, but only after discussing the risks and benefits with the person and reaching a shared decision. If a person opts to have a biopsy, offer systematic prostate biopsy.</li></ul>The approach of using mpMRI before biopsy in all men fit for active treatment has recently been mandated by NHS England.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>The National Comprehensive Cancer Network (NCCN)<a class="elsevierStyleCrossRef" href="#bib0055">11</a> guidelines stated it is too early to make recommendations on routinely using mpMRI for biopsy naive patients. The UK is the only national guideline to mandate the use of MRI at the start of active surveillance, while the EAU has suggested its use in active surveillance with a grade B recommendation<a class="elsevierStyleCrossRef" href="#bib0015">3</a> and the NCCN considers the inclusion of mpMRI in active surveillance protocol still debatable. For men with an initial negative TRUS biopsy, both the EAU and the NCCN Guidelines recommend MRI in men with a clinical suspicion of prostate cancer.<a class="elsevierStyleCrossRefs" href="#bib0015">3,11</a>The EAU guidelines panel recently published a meta-analysis examining the Negative Predictive Value (NPV) of mpMRI prior to initial biopsy and concluded that although there is potential for the test to be used as a triage for biopsy, it is still not sufficiently accurate at the present.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>The AUA Early Detection Guidelines describe mpMRI as a “secondary test with potential utility for determining the need for a prostate biopsy, but with unproven benefit” and devoid of evidence that it will increase the ratio of benefits to harm.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> It should be noted that this guideline was first published in 2013 and revised in 2015 when the use of mpMRI and its evidence was still in its infancy.The role of imaging in clinical diagnosis (mpMRI)EAU Guidelines<a class="elsevierStyleCrossRef" href="#bib0015">3</a> recommendations are perform mpMRI before repeat biopsy when clinical suspicion of PCa persists in spite of negative biopsies (level of evidence 1a) and when mpMRI is positive (PIRADS ≥ 3) perform targeted biopsy only (level of evidence 2a) and when mpMRI is negative (PIRADS ≤ 2 and clinical suspicion of prostate cancer is high perform systematic biopsy based on shared decision making with the patient.In biopsy naive patients, this year the recommendation of EAU guidelines is perform mpMRI before prostate biopsy (level of evidence 1a) and when mpMRI is positive (PIRADS ≥ 3) combine targeted and systematic biopsy (level of evidence 2a); when mpMRI is negative and clinical suspicion of prostate cancer is high, perform systematic biopsy is based on shared decision making with the patient.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>In the last decade, recent advances in imaging have enabled more accurate detection and characterization of suspicious lesions within the prostate. In addition to conventional T2-weighted anatomical sequences, mpMRI combines functional techniques such as diffusion-weighted MRI (DWI), dynamic contrast enhanced MRI (DCE) and MR spectroscopy (MRSI). The combination of these sequences in detecting PCa has been extensively studied in recent years.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Correlation with radical prostatectomy shows that mpMRI, associating T2-weighted imaging with at least one functional imaging technique (DWI, DCE, H1-spectroscopy) has good sensitivity for the detection and localization of Gleason Score (GS) ≥7 cancers.<a class="elsevierStyleCrossRefs" href="#bib0075">15,16</a>As a result, mpMRI is increasingly performed before prostate biopsy. Theoretically, pre-biopsy mpMRI could be used in two different ways: <ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025">1)the most challenging situation: using mpMRI as a triage test before biopsy. In this diagnostic pathway, only MRI-TBx would be performed in case of a positive mpMRI. Patients with a negative mpMRI would not undergo prostate biopsy at all.</li><li class="elsevierStyleListItem" id="lsti0030">2)mpMRI to improve the detection of clinically significant PCa(csPCa). In this diagnostic pathway, magnetic resonance imaging-targeted biopsies (MRI-TBx) would be added to systematic biopsies in case of a positive mpMRI, and systematic biopsies would be performed in all patients with a negative mpMRI.</li></ul>With respect to point number 1<a class="elsevierStyleCrossRef" href="#bib0085">17</a> whether systematic biopsies can be omitted in patients (or prostate lobes) with negative mpMRI depends on the NPV of mpMRI. A single-center RCT recently randomized 212 biopsy-naive men in two arms. Patients in arm A underwent pre-biopsy mpMRI and TBx only when mpMRI was positive (arm A+) and systematic biopsy when mpMRI was negative (arm A-). Patients in arm B underwent systematic biopsy without any mpMRI. The detection rates for csPCa (GS ≥ 3 + 4 or CCL ≥ 5 mm) were 56.8%, 3.8%, and 18.1% in arms A+, A- and B, respectively (p < 0. A multicenter, paired-cohort, confirmatory study performed in the United Kingdom and published in the Lancet (PROMIS) is one of the highest quality studies for using MRI to assist in the diagnosis of prostate cancer.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> This study enrolled men who had not undergone previous prostate biopsy but had an elevated PSA and underwent an MRI followed by both transperineal mapping biopsy (cores obtained at 5 mm intervals) and TRUSB. Using a definition of Gleason score ≥4 + 3 or cancer core length ≥6 mm for clinically significant disease, the reported sensitivity of mpMRI in this cohort was 93% (95% confidence interval [CI], 88%–96%). This was significantly greater than the sensitivity for TRUSB (48%; 95% CI, 42%–55%). However, there is ongoing debate regarding the amount of pattern 4 disease required for cancer to be considered clinically significant.<a class="elsevierStyleCrossRefs" href="#bib0095">19,20</a> Hence, when the definition includes the presence of any pattern 4 disease, the sensitivity of mpMRI decreases to 88% (95% CI, 84%–91%) which still significantly outperforms TRUSB. Importantly, this study demonstrates that mpMRI has a high negative predictive value (NPV) of 89% (95% CI, 83%–94%) if using the former definition for significant disease or 76% [95%CI, 69%–82%] if any Gleason score ≥3 + 4 cancer is considered significant. Although this data is somewhat reassuring that a negative mpMRI can rule out the presence of significant cancer, relying on it solely as a triage test would lead to aggressive cancer being missed in a quarter of the cases. There are further concerns regarding the generalizability of these results to routine clinical practice. This study was performed in a center of clinical excellence where radiologists and biopsy operators were highly trained and experienced and thus this level of expertise may not be present across all institutions which would impact the diagnostic performance of the test. The results of PROMIS are supported by a study of 388 Australian<a class="elsevierStyleCrossRef" href="#bib0105">21</a> men who underwent mpMRI and transperineal template-guided mapping biopsy in addition to targeted biopsy if any suspicious lesions were identified. A Prostate Imaging Reporting and Data System (PIRADS) 3–5 lesion was identified in 77% cases and mpMRI demonstrated a sensitivity of 95.8% in the detection of clinically significant disease. Two thirds of the missed cancers were either Gleason score 6 or had no more than 10% of pattern 4 disease. Additionally, an anatomic concordance analysis performed between mpMRI and mapping biopsy demonstrated 97% agreement.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>The recent PRECISION study<a class="elsevierStyleCrossRef" href="#bib0110">22</a> has assessed in a randomized controlled trial where men either had a standard biopsy or an MRI-targeted biopsy. Men in the standard biopsy arm had 26% clinically significant cancer and 22% clinically insignificant cancer (with significance deemed as any Gleason 7 or above), while in the MRI arm 28% of men avoided biopsy, 38% had clinically significant disease and 9% had clinically insignificant disease. PRECISION was an analysis of 2 different pathway approaches, showing clear advantages to the MRI-targeted pathway. However, questions have been raised about the potential advantage of adding standard cores to MRI targeted cores, and in using standard sampling in men with a negative MRI. This provides level one evidence that MRI and targeted biopsy should be included in the work-up of patients being considered for primary biopsy. However, it is not clear whether these results can be replicated in non-specialist settings because all radiologists involved in this trial were highly experienced, reporting on a median 300 mpMRIs per year. However, two other randomized studies found no additional benefit of performing mpMRI and targeted biopsy if the MRI was positive compared to systematic biopsy in all patients.<a class="elsevierStyleCrossRefs" href="#bib0115">23,24</a> In light of these conflicting results, further studies are required to characterize whether mpMRI and subsequent targeted biopsy provides additional benefit in this population. The results from non-randomized studies have demonstrated that 89% fewer low-risk cancers were diagnosed with Magnetic Resonance Guided Biopsy (MRGB) compared to TRUSB.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Considering that most institutions are yet to overcome the learning curve of mpMRI and subsequent MRGB, there is a considerable risk of missing significant cancer by omitting systematic biopsy and this is not recommended, nor is it widely practiced.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>In MRI-FIRST<a class="elsevierStyleCrossRef" href="#bib0135">27</a> (a prospective multicenter study in biopsy-naive patients that compared, in the same patients, the detection of ISUP grade group 2 or higher cancers, obtained by 12–14 core systematic biopsy and 3–6 core targeted biopsy) authors use three clinically significant prostate cancer (csPCa) definitions, based on the 2014 ISUP classification: grade group 2 or higher tumors (csPCa-A); grade group 1 tumor with maximum cancer core length (MCCL) of 6 mm or longer or grade group 2 or higher tumors (csPCa-B), and grade group 3 or higher tumors (csPCa-C). The detection of clinically significant prostate cancer (csPCa) did not differ between targeted biopsy and systematic biopsy. Detection of csPCa-B also did not differ between the two biopsy methods. For detection of csPCa-A and csPCa-B, detection improved when both systematic and targeted biopsy were combined. Detection of csPCa-C was significantly lower with systematic biopsy than with targeted biopsy, and targeted biopsy detected significantly fewer non-Clinically significant prostate cancer tumors than did systematic biopsy. Authors observed a difference of 2·4 percentage points between the detection of ISUP grade group 2 or higher tumors obtained by systematic biopsy and targeted biopsy, which is notably smaller than that reported in the PRECISION study.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Taken together, these results and those of the PRECISION trial strongly suggest that targeted biopsy has added value in biopsy-naive patients and improves the detection of clinically significant prostate cancer. However, the results of MRI-FIRST do nuance the results of the PRECISION trial. First, the added value of targeted biopsy seems to depend on the definition of clinically significant prostate cancer, which needs to be standardized. Second, the added value of systematic biopsy might still be substantial in patients having targeted biopsy, at least for the diagnosis of ISUP group grade 2 or higher cancers, and therefore the conditions remain to be defined under which systematic biopsy could be safely avoided in patients who had a pre-biopsy multiparametric.Recently, van der Leest<a class="elsevierStyleCrossRef" href="#bib0140">28</a> conducted a prospective, multicenter (4 M), clinical effectiveness study that compared head-to-head mpMRI + MR-guided biopsy (MRGB) with the transrectal ultrasound-guided biopsy (TRUSGB) pathway in biopsy-naïve men at risk of prostate cancer. The major strength of this study is its quality-controlled, multicenter, head-to-head design. It confirms the larger body of research and clinical experience on combined mpMRI and MRGB for the detection and localization of csPCa in biopsy-naïve patients. This paper makes multiple contributions to existing literature where there is controversy regarding its use for biopsy-naïve men. The study provides level 1a evidence that the mpMRI pathway is noninferior to the TRUSGB pathway in biopsy- naïve men with regard to significant disease detection but is superior for detecting fewer insignificant cancers and supports the “no immediate biopsy approach” after non- suspicious mpMRI scans. Similar to other studies, they show that TRUSGB yields of csPCa in nonsuspicious mpMRI patients are low (4%) Furthermore, not performing TRUSGB in these patients results in avoidance of complicated UTI/sepsis in 2.9%. The proportion of men avoiding biopsy is almost twice that reported by the PROMIS and PRECISION trials—27% and 28%, respectively.<a class="elsevierStyleCrossRefs" href="#bib0090">18,22</a> In the PROMIS study, this was at the cost of underdetection of csPCa of 24% (38/158) found on template mapping biopsy using the csPCa definition of GG ≥ 2 (GS ≥ 3 + 4). However, for TRUSGB the csPCa yield in nonsuspicious mpMRI cases was only 5.1% (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>)<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>According to the different papers published there are some limitations to take in consideration: <ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0035">-First, not all studies reported explicit adoption of the STAndards of Reporting for MRI-Targeted biopsy studies (START) recommendations<a class="elsevierStyleCrossRef" href="#bib0135">27</a> and of the PRECISE recommendations for reporting mpMRI in men in active surveillance.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> Consequently, for some studies, data regarding PCa detection rate are the results of an interpretation and extraction from the text of the study itself.</li><li class="elsevierStyleListItem" id="lsti0040">-Second, the definition of csPCa varied among the studies. Consequently, the comparison between the results are affected by a bias of definition. The greatest variability in the definition of csPCa was in the prior positive biopsy group, where some centers only include men with Gleason 3 + 3 disease, and others also include men with lower volume Gleason 3 + 4.</li><li class="elsevierStyleListItem" id="lsti0045">-Third, there is a lack of randomized data to answer the question (the utility of adding standard biopsies to MRI-TBx) except by the recent PRECISION publication<a class="elsevierStyleCrossRef" href="#bib0110">22</a> gives a clear answer to the greater utility of MRI-TBx compared to TRUS-Bx, the utility of adding standard biopsy to MRI-TBx was not addressed.</li><li class="elsevierStyleListItem" id="lsti0050">-Fourth, there was a wide heterogeneity among the included studies, regarding the mpMRI cut-off used to trigger a targeted biopsy. The reason for this diversity is the lack of evidence regarding the management of the so called “indeterminate lesions” (i.e., PI-RADS score 3 or Likert score 3). A recently published systematic review regarding this topic reported a rate of csPCa ranging from 4.4 to 11.3% among men with a PI-RADS 3 lesion detected by mpMRI.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> In order to decrease the number of biopsies and the risk of overdiagnosis, a strategy based on close surveillance using PSA monitoring and mpMRI for a rising PSA might be considered in the management of patients with indeterminate mpMRI lesions.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> The yield of clinically significant cancers amongst PIRADS 3 lesions have varied across the literature. Employing additional tests, including biomarkers, may assist with differentiating ‘high-risk’ PIRADS 3 lesions from ‘low risk’. Nonetheless, with the aim to more accurately inform the patient discussion, larger studies with longer follow-up would be helpful.</li><li class="elsevierStyleListItem" id="lsti0055">-Fiftht-test.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> In this cohort, mpMRI missed 26% of clinically significant cancers. The study did report that mpMRI was liable to missing lesions located in the dorsolateral segments (58%) and the apex (37%). On the other hand, it did demonstrate improved diagnosis of anterior lesions.<a class="elsevierStyleCrossRef" href="#bib0150">30</a></li></ul>Clinical implicationsTo summarize our findings in all men due to undergo biopsy, irrespective of previous biopsy status, MRI-TBx is of value in increasing the diagnosis of csPCa, with greatest benefit in men with prior negative biopsies. The addition of MRI-TBx did not increase the detection of insignificant PCa. Second, in the presence of a positive mpMRI, MRI-TBx was superior to standard TRUS-Bx in csPCa detection in all men. Finally, mpMRI is characterized by a high NPV and few csPCa are missed by this approach, although this does vary across studies (range 0–21%). Guidelines panels are still cautious in advising the introduction of mpMRI in every setting of PCa diagnosis. The advent of PI-RADS score v.2<a class="elsevierStyleCrossRef" href="#bib0155">31</a> is expected to significantly improve the standardization and decrease the variability in interpretation and reporting, and further confirmation of this is awaited. PI-RADS version 2 has been widely adopted and tested in clinical practice, with experience highlighting areas of ambiguity, poor performance, and reduced inter-reader variability. Version 2.1 makes several minor modifications aimed at addressing these issues and simplifying the scoring system without changing the overall framework for acquisition or interpretation using the principles of the dominant sequence paradigm. Although biparametric MRI is now acknowledged, concerns are noted, and mpMRI remains advised in a range of scenarios. PI-RADS remains an assessment based on image features alone; however, other clinical factors may also, appropriately influence decisions to biopsy or not. As with prior versions, further research is encouraged to assess the accuracy, reproducibility, and interobserver agreement of v2.1 and to identify any improvements that may aid in the evolution of version 3.<a class="elsevierStyleCrossRef" href="#bib0160">32</a>Active surveillance (AS) has been increasingly adopted as a conservative management approach for patients with low- risk prostate cancer and selected men with intermediate- risk prostate cancer to avoid or delay unnecessary treatment until higher- risk disease is evident. Several AS programs are available, with different selection criteria. Growing evidence suggests that mpMRI is being increasingly used in the setting of AS. A systematic review showed that mpMRI is useful for detecting clinically significant prostate cancer in men eligible for AS, reporting that 70% of these men have a positive mpMRI.<a class="elsevierStyleCrossRef" href="#bib0165">33</a>The limitations related to the use of mpMRI in clinical practice are its limited availability, relatively high cost in some healthcare settings, and the presence of interobserver variability amongst differently experienced radiologists. A recent analysis demonstrated that the total cost of the mpMRI strategy across the care pathway is similar to the cost of standard of care, due to a reduction in overdiagnosis and overtreatment offsetting the initial costs of MRI.<a class="elsevierStyleCrossRefs" href="#bib0170">34,35</a>FutureNot atypical for new technologies, the adoption of mpMRI prior to initial biopsy has outpaced the evidence to support this practice. Despite the majority of evidence being of low-quality, the results of PROMIS provides high-quality data to justify the use of mpMRI to triage patients for biopsy. However, this study is a standalone and there are concerns surrounding the generalizability of its results to the wider community. The FUTURE trial<a class="elsevierStyleCrossRef" href="#bib0180">36</a> compared overall PCa and csPCa detection rates of the three Targeted Biopsy (TB) techniques and aimed to identify whether there was a superior technique regarding diagnostic efficacy in a repeat biopsy setting (MRI-transrectal ultrasound (TRUS) fusion TB (FUS-TB), cognitive registration TRUS TB (COG-TB), or in-bore MRI TB (MRI-TB). In men with prior negative prostate biopsies and a persistent suspicion of prostate cancer, the rate of CSRs (PIRADS ≥ 3) on mpMRI was 35%. If TB of these regions is performed, the detection rate would be 49% for PCa and 33% for csPCa. Based on this multicenter RCT, there were no significant differences in the detection rates of (cs)PCa among the three techniques of mpMRI-based TB. Consequently, other factors (such as local experience, availability, and costs) should be evaluated when determining which technique(s) to implement. Inter-reader variability remains an unsolved problem, particularly when mpMRI is used in centers with little experience. To overcome this issue, during the past 5 years, efforts have been made to implement computer- aided diagnosis (CAD). The aim of CAD is to bypass interobserver variability through the use of machine learning algorithms based on quantitative analyses that are able to discriminate areas within the prostate gland in which clinically significant prostate cancer is suspected. Results regarding the use of CAD in mpMRI of the prostate are still preliminary, but the first comparison between CAD and PI- RADS v2 showed promising results.Current clinical practice uses mpMRI scanners with magnetic field strengths of either 1.5 T or 3 T. An increased signal: noise ratio is provided by 3 T scanning, which enables increased spatial and temporal resolution. However, increased field strengths might cause more artefacts. Initial studies comparing 1.5 T with 3 T mpMRI reported comparable accuracy in cancer localization and local staging. Moreover, 1.5 T, performed using both endorectal and surface coils, seemed to show superior image quality and tumor delineation compared with 3 T. Direct comparisons in homogeneous cohorts without the use of endorectal coil showed that the use of 1.5 T did not compromise the diagnostic accuracy of mpMRI in terms of PI- RADS scoring, achieving excellent NPV and moderate PPV (94% and 52%, respectively). Furthermore, no significant differences between the two field strengths were observed in a meta- analysis.<a class="elsevierStyleCrossRefs" href="#bib0185">37–39</a>State-of-the-art full diagnostic mp-MRI of the prostate performed according to the Prostate Imaging Reporting and Data System (PI-RADS) v2 guidelines, consists of T2- weighted imaging (T2WI) in three orthogonal planes, and diffusion-weighted imaging (DWI) and dynamic contrast- enhanced (DCE) imaging after administration of intravenous contrast material. According to the PI-RADS v2 system, the role of DCE imaging is being reserved for the clarification of equivocal abnormalities in the peripheral zone. The full PI-RADS-compliant protocol is, however, time-consuming and costly, and has implementation challenges where MRI accessibility is limited. This may restrict the routine use of MRI as a triage test in men with elevated PSA. Van der Leest et al. recently<a class="elsevierStyleCrossRef" href="#bib0200">40</a> have compared the diagnostic performance of monoplanar (“fast” biparametric MRI [bp-MRI]) and triplanar noncontrast bp-MRI with that of the current contrast-enhanced multiparametric MRI (mp-MRI) in the detection of high-grade PCa in biopsy-naïve men. A prospective, multireader, head-to-head study included 626 biopsy-naïve men, between February 2015 and February 2018.They concluded Short MRI protocols can improve prostate MRI accessibility at a lower direct cost. For fast bp-MRI, this is at the cost of +/- 2% more biopsies and +/- 1% more overdetection of low-grade PCa.Although mpMRI has been demonstrated to be a potentially cost-effective strategy pre-biopsy, benefits would be amplified by improving patient selection. This could be achieved by developing nomograms or by attempting to correlate biomarker results to mpMRI findings.<a class="elsevierStyleCrossRefs" href="#bib0210">42,43</a>The introduction of mpMRI as a triage test might change the traditional diagnostic pathway of prostate cancer (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Cost-effectivenessThe introduction of mpMRI within the prostate cancer diagnostic pathway has advantages from a diagnostic perspective, but assessing its cost- effectiveness is important. One of the earliest studies addressing this topic was conducted by de Rooij et al.,<a class="elsevierStyleCrossRef" href="#bib0205">41</a> who developed a model based on two diagnostic strategies: standard of care based on performing TRUS- guided biopsy in patients with suspected prostate cancer and an experimental mpMRI strategy based on offering mpMRI to men referred for suspected prostate cancer, with subsequent mpMRI- targeted biopsy if the mpMRI is positive, or routine follow- up monitoring if mpMRI is negative. In both arms, patients underwent active treatment (radical prostatectomy or radiotherapy) when clinically significant prostate cancer was diagnosed. The outcomes were costs, quality- adjusted life years (QALYs) and incremental cost- effectiveness ratios (ICERs). The authors concluded that, although the experimental mpMRI strategy is initially more expensive (expected costs of the mpMRI strategy were €31 higher than those for the TRUS- guided biopsy strategy), these extra costs are compensated for by the reduction in treatment costs resulting from fewer false positives and an improved Estimation of tumor aggressiveness compared with the standard of care TRUS- guided biopsy pathway.<a class="elsevierStyleCrossRefs" href="#bib0215">43,44</a>ConclusionsOver the past decade, prostate mpMRI has been an exciting development that seems likely to change the standard prostate cancer diagnostic pathway. This test is useful in a number of different patient populations and has the potential to serve as a triage test. Results of studies comparing mpMRI- targeted biopsy with systematic biopsy suggest the addition of mpMRI-targeted biopsy to systematic biopsy and strategies such as mpMRI-targeted biopsy alone are feasible. Use of biomarkers combined with mpMRI information can improve the performance of the mpMRI in identifying clinically significant cancer. Despite the abovementioned limitations, an image-based mpMRI- strategy seems to improve patient quality-of-life by reducing overdiagnosis and overtreatment at comparable to the current standard TRUSbx approach." "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:3 [ "identificador" => "xres1330671" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1226037" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1330672" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1226036" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Recommendations international guidelines" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "The role of imaging in clinical diagnosis (mpMRI)" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Clinical implications" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Future" ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "Cost-effectiveness" ] ] ] 5 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusions" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-08-08" "fechaAceptado" => "2019-08-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1226037" "palabras" => array:4 [ 0 => "Prostate cancer detection" 1 => "Multiparametric magnetic resonance imaging" 2 => "Diagnosis" 3 => "Prostate biopsy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1226036" "palabras" => array:4 [ 0 => "Detección de cáncer de próstata" 1 => "Resonancia magnética multiparamétrica" 2 => "Diagnóstico" 3 => "Biopsia de próstata" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Prostate cancer (PCa) is the second leading cause of cancer-related mortality and the most frequently diagnosed male malignant disease among men. The manifestation of PCa ranges from indolent to highly aggressive disease and due to this high variation in PCa progression, the diagnosis and subsequent treatment planning can be challenging. The current diagnostic approach with PSA testing and digital rectal examination followed by transrectal ultrasound biopsies (TRUS-bx) lack in both sensitivity and specificity in PCa detection and offers limited information about the aggressiveness and stage of the cancer. Scientific work supports the rapidly growing use of multiparametric magnetic resonance imaging (mp-MRI) as the most sensitive and specific imaging tool for detection, lesion characterization and staging of Pca. Therefore, we carried out an updated review of Magnetic Resonance Imaging in the diagnostic prostate cancer reviewing the latest papers published in Pub Med." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El cáncer de próstata (CP) es la segunda causa principal de mortalidad por cáncer y la enfermedad diagnosticada con mayor frecuencia en la población masculina. El CP se manifiesta de diversas maneras; desde enfermedad indolente a altamente agresiva. A esto se debe la complejidad de su diagnóstico y de la elección del tratamiento adecuado. El enfoque utilizado actualmente, con pruebas de PSA y examen rectal digital seguido de biopsia transrectal ecodirigida (BTE) carece de sensibilidad y especificidad en la detección de CP y ofrece información limitada sobre la agresividad y el estadio del cáncer. La evidencia científica respalda el creciente uso de la resonancia magnética multiparamétrica (RMmp) como la herramienta de imagen más sensible y específica para la detección, caracterización de lesiones y estadificación del CP. El presente estudio hace una revisión actualizada del rol de la resonancia magnética en el diagnóstico de cáncer de próstata, revisando los últimos artículos publicados en PubMed." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Álvarez-Maestro M. La resonancia magnética como herramienta para el diagnóstico del cáncer de próstata: nuevas evidencias y posicionamiento de la ESUT (EAU Section of Uro-Technology). Actas Urol Esp. 2020;44:148–155." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 675 "Ancho" => 1667 "Tamanyo" => 72805 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "The use of multiparametric MRI (mpMRI) as a triage test enables all men with negative mpMRI to be spared from receiving a biopsy, opting for a surveillance strategy mainly based on the use of PSA and follow- up mpMRI. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article)." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "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 \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">Study \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">Precision \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">MRI-1st \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">4 M \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">Year \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2019 \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">2019 \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">Country \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">UK \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">France \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">Netherlands \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">N \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">500 \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">251 \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">626 \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">PSA \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">Up to 20 ng/mL \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">Up to 20 ng/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥ 3 ng/mL \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">Biopsy \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">Systematic vs Target \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">Systematic vs Target + Systematic \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">Systematic vs Target + Systematic \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">Targeting \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">Cognitive - fusion \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">Cognitive - fusion \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">In bore \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">Systematic (%)ISUP 1 csPCaISUP 2 insPCa \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">2622 \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">3020 \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">2325 \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">Target (%)ISUP 1 csPCaISUP 2 insPCa \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">389 \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2514 \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">Patients avoiding biopsy (%) \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">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18-21 \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">49 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2280556.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Summary of precision, mri-first and 4 m clinical studies (csPCa: significant prostate cancer; insPCa: insignificant prostate cancer)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:44 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Critical role of prostate biopsy mortality in the number of years of life gained and lost within a prostate cancer screening programme" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. 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Magnetic resonance as imaging diagnostic tool in prostate cancer: New evidences-The EAU section of uro-technology position

La resonancia magnética como herramienta para el diagnóstico del cáncer de próstata: nuevas evidencias y posicionamiento de la ESUT (EAU Section of Uro-Technology)

M. Álvarez-Maestroa,b,

Corresponding author

malvarezmaestro@hotmail.com

Corresponding author.

, J. Gómez Rivasa,b, J. Quesada Olartea, D. Carrión Monsalvea, C. Trelles Guzmana, C. Ballesterosa, L.M. Quintanaa, A. Aguilera Bazána,b, L. Martínez-Piñeiroa,b, E. Liatsikosc, E. Barretd

a Departamento de Urología, Hospital Universitario La Paz, Madrid, Spain

b Instituto de Investigación, Hospital Universitario La Paz (IdiPAZ), Madrid, Spain

c Departamento de Urología, Universidad de Patras, Patras, Grecia

d Departamento de Urologia, Instituto Mutualista Montsouris, Paris, France

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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The use of multiparametric MRI &#40;mpMRI&#41; as a triage test enables all men with negative mpMRI to be spared from receiving a biopsy&#44; opting for a surveillance strategy mainly based on the use of PSA and follow- up mpMRI&#46; &#40;For interpretation of the references to colour in this figure legend&#44; the reader is referred to the web version of this article&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In recent years&#44; evidence has accrued to support the introduction of multiparametric magnetic resonance imaging &#40;mpMRI&#41; in the prostate cancer &#40;PCa&#41; diagnostic pathway&#46; The exact role of mpMRI in different settings is not widely agreed&#46; In this review&#44; we look at the use of MRI in the prostate cancer diagnostic&#46; Prostate cancer is the most commonly diagnosed solid-organ malignancy amongst men in the USA&#46; The current diagnostic pathway for PCa is based on the use of prostatic specific antigen &#40;PSA&#41; and digital rectal examination &#40;DRE&#41; to inform the decision to undertake systematic transrectal ultrasound-guided biopsy &#40;TRUSBx&#41;&#46; Despite recommendations to the contrary&#44; men still most commonly present to clinicians for evaluation following an elevated prostate specific antigen &#40;PSA&#41; test&#46; PSA has poor specificity for aggressive cancer&#46; This diagnostic pathway has led&#44; over the years&#44; to an increase in PCa incidence and a slight reduction in cancer-specific mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Overdiagnosis and overtreatment of indolent prostate cancer represent important drawbacks of this approach&#44; that have not been adequately addressed by the use of active surveillance for men with low risk disease&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In an attempt to curb these latter two issues there have been extensive efforts to improve patient selection&#46; The use of biomarkers such as PHI&#44; 4Kscore&#44; and SelectMDx has demonstrated the potential to aid risk stratification of patients&#44; but these are not yet widely adopted in routine clinical practice and the latter two have not received USA Food and Drug Administration clearance to date&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Similarly&#44; risk calculators have also been used as a risk-stratification tool to improve patient selection&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The typical sampling strategy is a 10&#8211;12 core TRUS biopsy with cores directed principally at the base&#44; midgland and apex of the peripheral zone of each of the left and right lobes of the prostate&#46; The use of anteriorly directed cores is not recommended at first biopsy&#44; according to the most recent European Association of Urology guidelines 2019&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Ten to twelve core biopsies are recommended in larger prostates&#44; with&#8239;&#62;&#8239;twelve cores not being significantly more conclusive&#46; <span class="elsevierStyleItalic">Ultrasound &#40;US&#41;-guided biopsy is now the standard of care&#46;</span> Prostate biopsy is performed by either the transrectal or transperineal approach&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Some evidence suggests reduced infection risk with the transperineal route&#46; Sextant biopsy is no longer considered adequate&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Grey-scale TRUS is not reliable at detecting PCa&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Thus&#44; there is no evidence that US-targeted biopsies can replace systematic biopsies&#46; New sonographic modalities such as sonoelastography and contrast-enhanced US are still under investigation and not ready for routine use&#46; Although this biopsy strategy is superior to the initial &#8220;random systematic&#8221; 6-core TRUS-Bx&#44; as reported by Stamey and Hodge&#44; a meta-analysis that investigated the comparison between 12-core TRUS-Bx and whole gland radical prostatectomy specimens&#44; found false negative rates for TRUS-Bx of up to 49&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In addition to biomarkers and risk calculators&#44; there has been considerable progress in the landscape of prostate imaging&#46; Multiparametric magnetic resonance imaging &#40;mpMRI&#41; has come to the forefront of local tumor imaging over the last decade&#46; This has most commonly been used in the setting of previous negative TRUSB&#44; but the observed utility has prompted clinicians to also adopt it in primary diagnostic pathway&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In keeping with this&#44; the evidence for the use of mpMRI is primarily for the population of men with a previous negative TRUSB&#46; There is growing interest in the use of mpMRI of the prostate to refine the diagnostic pathway of PCa&#44; improve risk stratification&#44; and diagnose only those men who could benefit from active treatment&#46; Prostate MRI was initially introduced in late 1980s as an imaging technique for local staging of PCa&#44; identifying extracapsular extension and seminal vesicle invasion&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Despite the promising role of mpMRI in the diagnostic pathway of PCa&#44; international panels of experts are cautious in advising the use of MRI and subsequent MRI-TBx in every setting of PCa diagnosis&#46; In particular there is much debate about the need for systematic cores in men having MRI-targeted biopsies&#44; and in those men with a negative MRI&#46;</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Recommendations international guidelines</span><p id="par0020" class="elsevierStylePara elsevierViewall">The UK NICE Guidelines 2019 recommends&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0025" class="elsevierStylePara elsevierViewall">Do not routinely offer multiparametric MRI to people with prostate cancer who are not going to be able to have radical treatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0030" class="elsevierStylePara elsevierViewall">Offer multiparametric MRI as the first-line investigation for people with suspected clinically localized prostate cancer&#46; Report the results using a 5&#8209;point Likert scale&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall">Offer multiparametric MRI-influenced prostate biopsy to people whose Likert score is 3 or more&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">Consider omitting a prostate biopsy for people whose multiparametric MRI Likert score is 1 or 2&#44; but only after discussing the risks and benefits with the person and reaching a shared decision&#46; If a person opts to have a biopsy&#44; offer systematic prostate biopsy&#46;</p></li></ul></p><p id="par0045" class="elsevierStylePara elsevierViewall">The approach of using mpMRI before biopsy in all men fit for active treatment has recently been mandated by NHS England&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The National Comprehensive Cancer Network &#40;NCCN&#41;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> guidelines stated it is too early to make recommendations on routinely using mpMRI for biopsy naive patients&#46; The UK is the only national guideline to mandate the use of MRI at the start of active surveillance&#44; while the EAU has suggested its use in active surveillance with a grade B recommendation<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and the NCCN considers the inclusion of mpMRI in active surveillance protocol still debatable&#46; For men with an initial negative TRUS biopsy&#44; both the EAU and the NCCN Guidelines recommend MRI in men with a clinical suspicion of prostate cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;11</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The EAU guidelines panel recently published a meta-analysis examining the Negative Predictive Value &#40;NPV&#41; of mpMRI prior to initial biopsy and concluded that although there is potential for the test to be used as a triage for biopsy&#44; it is still not sufficiently accurate at the present&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The AUA Early Detection Guidelines describe mpMRI as a &#8220;secondary test with potential utility for determining the need for a prostate biopsy&#44; but with unproven benefit&#8221; and devoid of evidence that it will increase the ratio of benefits to harm&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> It should be noted that this guideline was first published in 2013 and revised in 2015 when the use of mpMRI and its evidence was still in its infancy&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">The role of imaging in clinical diagnosis &#40;mpMRI&#41;</span><p id="par0065" class="elsevierStylePara elsevierViewall">EAU Guidelines<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> recommendations are perform mpMRI before repeat biopsy when clinical suspicion of PCa persists in spite of negative biopsies &#40;level of evidence 1a&#41; and when mpMRI is positive &#40;PIRADS&#8239;&#8805;&#8239;3&#41; perform targeted biopsy only &#40;level of evidence 2a&#41; and when mpMRI is negative &#40;PIRADS&#8239;&#8804;&#8239;2 and clinical suspicion of prostate cancer is high perform systematic biopsy based on shared decision making with the patient&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In biopsy naive patients&#44; this year the recommendation of EAU guidelines is perform mpMRI before prostate biopsy &#40;level of evidence 1a&#41; and when mpMRI is positive &#40;PIRADS&#8239;&#8805;&#8239;3&#41; combine targeted and systematic biopsy &#40;level of evidence 2a&#41;&#59; when mpMRI is negative and clinical suspicion of prostate cancer is high&#44; perform systematic biopsy is based on shared decision making with the patient&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In the last decade&#44; recent advances in imaging have enabled more accurate detection and characterization of suspicious lesions within the prostate&#46; In addition to conventional T2-weighted anatomical sequences&#44; mpMRI combines functional techniques such as diffusion-weighted MRI &#40;DWI&#41;&#44; dynamic contrast enhanced MRI &#40;DCE&#41; and MR spectroscopy &#40;MRSI&#41;&#46; The combination of these sequences in detecting PCa has been extensively studied in recent years&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Correlation with radical prostatectomy shows that mpMRI&#44; associating T2-weighted imaging with at least one functional imaging technique &#40;DWI&#44; DCE&#44; H1-spectroscopy&#41; has good sensitivity for the detection and localization of Gleason Score &#40;GS&#41; &#8805;7 cancers&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">As a result&#44; mpMRI is increasingly performed before prostate biopsy&#46; Theoretically&#44; pre-biopsy mpMRI could be used in two different ways&#58; <ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">1&#41;</span><p id="par0085" class="elsevierStylePara elsevierViewall">the most challenging situation&#58; using mpMRI as a triage test before biopsy&#46; In this diagnostic pathway&#44; only MRI-TBx would be performed in case of a positive mpMRI&#46; Patients with a negative mpMRI would not undergo prostate biopsy at all&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">2&#41;</span><p id="par0090" class="elsevierStylePara elsevierViewall">mpMRI to improve the detection of clinically significant PCa&#40;csPCa&#41;&#46; In this diagnostic pathway&#44; magnetic resonance imaging-targeted biopsies &#40;MRI-TBx&#41; would be added to systematic biopsies in case of a positive mpMRI&#44; and systematic biopsies would be performed in all patients with a negative mpMRI&#46;</p></li></ul></p><p id="par0095" class="elsevierStylePara elsevierViewall">With respect to point number 1<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> whether systematic biopsies can be omitted in patients &#40;or prostate lobes&#41; with negative mpMRI depends on the NPV of mpMRI&#46; A single-center RCT recently randomized 212 biopsy-naive men in two arms&#46; Patients in arm A underwent pre-biopsy mpMRI and TBx only when mpMRI was positive &#40;arm A&#43;&#41; and systematic biopsy when mpMRI was negative &#40;arm A-&#41;&#46; Patients in arm B underwent systematic biopsy without any mpMRI&#46; The detection rates for csPCa &#40;GS &#8805; 3&#8239;&#43;&#8239;4 or CCL&#8239;&#8805;&#8239;5&#8239;mm&#41; were 56&#46;8&#37;&#44; 3&#46;8&#37;&#44; and 18&#46;1&#37; in arms A&#43;&#44; A- and B&#44; respectively &#40;p&#8239;&#60;&#8239;0&#46; A multicenter&#44; paired-cohort&#44; confirmatory study performed in the United Kingdom and published in the Lancet &#40;PROMIS&#41; is one of the highest quality studies for using MRI to assist in the diagnosis of prostate cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> This study enrolled men who had not undergone previous prostate biopsy but had an elevated PSA and underwent an MRI followed by both transperineal mapping biopsy &#40;cores obtained at 5&#8239;mm intervals&#41; and TRUSB&#46; Using a definition of Gleason score &#8805;4&#8239;&#43;&#8239;3 or cancer core length &#8805;6&#8239;mm for clinically significant disease&#44; the reported sensitivity of mpMRI in this cohort was 93&#37; &#40;95&#37; confidence interval &#91;CI&#93;&#44; 88&#37;&#8211;96&#37;&#41;&#46; This was significantly greater than the sensitivity for TRUSB &#40;48&#37;&#59; 95&#37; CI&#44; 42&#37;&#8211;55&#37;&#41;&#46; However&#44; there is ongoing debate regarding the amount of pattern 4 disease required for cancer to be considered clinically significant&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a> Hence&#44; when the definition includes the presence of any pattern 4 disease&#44; the sensitivity of mpMRI decreases to 88&#37; &#40;95&#37; CI&#44; 84&#37;&#8211;91&#37;&#41; which still significantly outperforms TRUSB&#46; Importantly&#44; this study demonstrates that mpMRI has a high negative predictive value &#40;NPV&#41; of 89&#37; &#40;95&#37; CI&#44; 83&#37;&#8211;94&#37;&#41; if using the former definition for significant disease or 76&#37; &#91;95&#37;CI&#44; 69&#37;&#8211;82&#37;&#93; if any Gleason score &#8805;3&#8239;&#43;&#8239;4 cancer is considered significant&#46; Although this data is somewhat reassuring that a negative mpMRI can rule out the presence of significant cancer&#44; relying on it solely as a triage test would lead to aggressive cancer being missed in a quarter of the cases&#46; There are further concerns regarding the generalizability of these results to routine clinical practice&#46; This study was performed in a center of clinical excellence where radiologists and biopsy operators were highly trained and experienced and thus this level of expertise may not be present across all institutions which would impact the diagnostic performance of the test&#46; The results of PROMIS are supported by a study of 388 Australian<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> men who underwent mpMRI and transperineal template-guided mapping biopsy in addition to targeted biopsy if any suspicious lesions were identified&#46; A Prostate Imaging Reporting and Data System &#40;PIRADS&#41; 3&#8211;5 lesion was identified in 77&#37; cases and mpMRI demonstrated a sensitivity of 95&#46;8&#37; in the detection of clinically significant disease&#46; Two thirds of the missed cancers were either Gleason score 6 or had no more than 10&#37; of pattern 4 disease&#46; Additionally&#44; an anatomic concordance analysis performed between mpMRI and mapping biopsy demonstrated 97&#37; agreement&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The recent PRECISION study<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> has assessed in a randomized controlled trial where men either had a standard biopsy or an MRI-targeted biopsy&#46; Men in the standard biopsy arm had 26&#37; clinically significant cancer and 22&#37; clinically insignificant cancer &#40;with significance deemed as any Gleason 7 or above&#41;&#44; while in the MRI arm 28&#37; of men avoided biopsy&#44; 38&#37; had clinically significant disease and 9&#37; had clinically insignificant disease&#46; PRECISION was an analysis of 2 different pathway approaches&#44; showing clear advantages to the MRI-targeted pathway&#46; However&#44; questions have been raised about the potential advantage of adding standard cores to MRI targeted cores&#44; and in using standard sampling in men with a negative MRI&#46; This provides level one evidence that MRI and targeted biopsy should be included in the work-up of patients being considered for primary biopsy&#46; However&#44; it is not clear whether these results can be replicated in non-specialist settings because all radiologists involved in this trial were highly experienced&#44; reporting on a median 300 mpMRIs per year&#46; However&#44; two other randomized studies found no additional benefit of performing mpMRI and targeted biopsy if the MRI was positive compared to systematic biopsy in all patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;24</span></a> In light of these conflicting results&#44; further studies are required to characterize whether mpMRI and subsequent targeted biopsy provides additional benefit in this population&#46; The results from non-randomized studies have demonstrated that 89&#37; fewer low-risk cancers were diagnosed with Magnetic Resonance Guided Biopsy &#40;MRGB&#41; compared to TRUSB&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Considering that most institutions are yet to overcome the learning curve of mpMRI and subsequent MRGB&#44; there is a considerable risk of missing significant cancer by omitting systematic biopsy and this is not recommended&#44; nor is it widely practiced&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In MRI-FIRST<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> &#40;a prospective multicenter study in biopsy-naive patients that compared&#44; in the same patients&#44; the detection of ISUP grade group 2 or higher cancers&#44; obtained by 12&#8211;14 core systematic biopsy and 3&#8211;6 core targeted biopsy&#41; authors use three clinically significant prostate cancer &#40;csPCa&#41; definitions&#44; based on the 2014 ISUP classification&#58; grade group 2 or higher tumors &#40;csPCa-A&#41;&#59; grade group 1 tumor with maximum cancer core length &#40;MCCL&#41; of 6&#8239;mm or longer or grade group 2 or higher tumors &#40;csPCa-B&#41;&#44; and grade group 3 or higher tumors &#40;csPCa-C&#41;&#46; The detection of clinically significant prostate cancer &#40;csPCa&#41; did not differ between targeted biopsy and systematic biopsy&#46; Detection of csPCa-B also did not differ between the two biopsy methods&#46; For detection of csPCa-A and csPCa-B&#44; detection improved when both systematic and targeted biopsy were combined&#46; Detection of csPCa-C was significantly lower with systematic biopsy than with targeted biopsy&#44; and targeted biopsy detected significantly fewer non-Clinically significant prostate cancer tumors than did systematic biopsy&#46; Authors observed a difference of 2&#183;4 percentage points between the detection of ISUP grade group 2 or higher tumors obtained by systematic biopsy and targeted biopsy&#44; which is notably smaller than that reported in the PRECISION study&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Taken together&#44; these results and those of the PRECISION trial strongly suggest that targeted biopsy has added value in biopsy-naive patients and improves the detection of clinically significant prostate cancer&#46; However&#44; the results of MRI-FIRST do nuance the results of the PRECISION trial&#46; First&#44; the added value of targeted biopsy seems to depend on the definition of clinically significant prostate cancer&#44; which needs to be standardized&#46; Second&#44; the added value of systematic biopsy might still be substantial in patients having targeted biopsy&#44; at least for the diagnosis of ISUP group grade 2 or higher cancers&#44; and therefore the conditions remain to be defined under which systematic biopsy could be safely avoided in patients who had a pre-biopsy multiparametric&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Recently&#44; van der Leest<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> conducted a prospective&#44; multicenter &#40;4&#8239;M&#41;&#44; clinical effectiveness study that compared head-to-head mpMRI&#8239;&#43;&#8239;MR-guided biopsy &#40;MRGB&#41; with the transrectal ultrasound-guided biopsy &#40;TRUSGB&#41; pathway in biopsy-na&#239;ve men at risk of prostate cancer&#46; The major strength of this study is its quality-controlled&#44; multicenter&#44; head-to-head design&#46; It confirms the larger body of research and clinical experience on combined mpMRI and MRGB for the detection and localization of csPCa in biopsy-nai&#776;ve patients&#46; This paper makes multiple contributions to existing literature where there is controversy regarding its use for biopsy-nai&#776;ve men&#46; The study provides level 1a evidence that the mpMRI pathway is noninferior to the TRUSGB pathway in biopsy- nai&#776;ve men with regard to significant disease detection but is superior for detecting fewer insignificant cancers and supports the &#8220;no immediate biopsy approach&#8221; after non- suspicious mpMRI scans&#46; Similar to other studies&#44; they show that TRUSGB yields of csPCa in nonsuspicious mpMRI patients are low &#40;4&#37;&#41; Furthermore&#44; not performing TRUSGB in these patients results in avoidance of complicated UTI&#47;sepsis in 2&#46;9&#37;&#46; The proportion of men avoiding biopsy is almost twice that reported by the PROMIS and PRECISION trials&#8212;27&#37; and 28&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;22</span></a> In the PROMIS study&#44; this was at the cost of underdetection of csPCa of 24&#37; &#40;38&#47;158&#41; found on template mapping biopsy using the csPCa definition of GG&#8239;&#8805;&#8239;2 &#40;GS&#8239;&#8805;&#8239;3&#8239;&#43;&#8239;4&#41;&#46; However&#44; for TRUSGB the csPCa yield in nonsuspicious mpMRI cases was only 5&#46;1&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">According to the different papers published there are some limitations to take in consideration&#58; <ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">First</span>&#44; not all studies reported explicit adoption of the STAndards of Reporting for MRI-Targeted biopsy studies &#40;START&#41; recommendations<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and of the PRECISE recommendations for reporting mpMRI in men in active surveillance&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Consequently&#44; for some studies&#44; data regarding PCa detection rate are the results of an interpretation and extraction from the text of the study itself&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Second</span>&#44; the definition of csPCa varied among the studies&#46; Consequently&#44; the comparison between the results are affected by a bias of definition&#46; The greatest variability in the definition of csPCa was in the prior positive biopsy group&#44; where some centers only include men with Gleason 3&#8239;&#43;&#8239;3 disease&#44; and others also include men with lower volume Gleason 3&#8239;&#43;&#8239;4&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Third</span>&#44; there is a lack of randomized data to answer the question &#40;the utility of adding standard biopsies to MRI-TBx&#41; except by the recent PRECISION publication<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> gives a clear answer to the greater utility of MRI-TBx compared to TRUS-Bx&#44; the utility of adding standard biopsy to MRI-TBx was not addressed&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Fourth</span>&#44; there was a wide heterogeneity among the included studies&#44; regarding the mpMRI cut-off used to trigger a targeted biopsy&#46; The reason for this diversity is the lack of evidence regarding the management of the so called &#8220;indeterminate lesions&#8221; &#40;i&#46;e&#46;&#44; PI-RADS score 3 or Likert score 3&#41;&#46; A recently published systematic review regarding this topic reported a rate of csPCa ranging from 4&#46;4 to 11&#46;3&#37; among men with a PI-RADS 3 lesion detected by mpMRI&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> In order to decrease the number of biopsies and the risk of overdiagnosis&#44; a strategy based on close surveillance using PSA monitoring and mpMRI for a rising PSA might be considered in the management of patients with indeterminate mpMRI lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> The yield of clinically significant cancers amongst PIRADS 3 lesions have varied across the literature&#46; Employing additional tests&#44; including biomarkers&#44; may assist with differentiating &#8216;high-risk&#8217; PIRADS 3 lesions from &#8216;low risk&#8217;&#46; Nonetheless&#44; with the aim to more accurately inform the patient discussion&#44; larger studies with longer follow-up would be helpful&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Fifth</span>t-test&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> In this cohort&#44; mpMRI missed 26&#37; of clinically significant cancers&#46; The study did report that mpMRI was liable to missing lesions located in the dorsolateral segments &#40;58&#37;&#41; and the apex &#40;37&#37;&#41;&#46; On the other hand&#44; it did demonstrate improved diagnosis of anterior lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Clinical implications</span><p id="par0145" class="elsevierStylePara elsevierViewall">To summarize our findings in all men due to undergo biopsy&#44; irrespective of previous biopsy status&#44; MRI-TBx is of value in increasing the diagnosis of csPCa&#44; with greatest benefit in men with prior negative biopsies&#46; The addition of MRI-TBx did not increase the detection of insignificant PCa&#46; Second&#44; in the presence of a positive mpMRI&#44; MRI-TBx was superior to standard TRUS-Bx in csPCa detection in all men&#46; Finally&#44; mpMRI is characterized by a high NPV and few csPCa are missed by this approach&#44; although this does vary across studies &#40;range 0&#8211;21&#37;&#41;&#46; Guidelines panels are still cautious in advising the introduction of mpMRI in every setting of PCa diagnosis&#46; The advent of PI-RADS score v&#46;2<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> is expected to significantly improve the standardization and decrease the variability in interpretation and reporting&#44; and further confirmation of this is awaited&#46; PI-RADS version 2 has been widely adopted and tested in clinical practice&#44; with experience highlighting areas of ambiguity&#44; poor performance&#44; and reduced inter-reader variability&#46; Version 2&#46;1 makes several minor modifications aimed at addressing these issues and simplifying the scoring system without changing the overall framework for acquisition or interpretation using the principles of the dominant sequence paradigm&#46; Although biparametric MRI is now acknowledged&#44; concerns are noted&#44; and mpMRI remains advised in a range of scenarios&#46; PI-RADS remains an assessment based on image features alone&#59; however&#44; other clinical factors may also&#44; appropriately influence decisions to biopsy or not&#46; As with prior versions&#44; further research is encouraged to assess the accuracy&#44; reproducibility&#44; and interobserver agreement of v2&#46;1 and to identify any improvements that may aid in the evolution of version 3&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Active surveillance &#40;AS&#41; has been increasingly adopted as a conservative management approach for patients with low- risk prostate cancer and selected men with intermediate- risk prostate cancer to avoid or delay unnecessary treatment until higher- risk disease is evident&#46; Several AS programs are available&#44; with different selection criteria&#46; Growing evidence suggests that mpMRI is being increasingly used in the setting of AS&#46; A systematic review showed that mpMRI is useful for detecting clinically significant prostate cancer in men eligible for AS&#44; reporting that 70&#37; of these men have a positive mpMRI&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The limitations related to the use of mpMRI in clinical practice are its limited availability&#44; relatively high cost in some healthcare settings&#44; and the presence of interobserver variability amongst differently experienced radiologists&#46; A recent analysis demonstrated that the total cost of the mpMRI strategy across the care pathway is similar to the cost of standard of care&#44; due to a reduction in overdiagnosis and overtreatment offsetting the initial costs of MRI&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Future</span><p id="par0160" class="elsevierStylePara elsevierViewall">Not atypical for new technologies&#44; the adoption of mpMRI prior to initial biopsy has outpaced the evidence to support this practice&#46; Despite the majority of evidence being of low-quality&#44; the results of PROMIS provides high-quality data to justify the use of mpMRI to triage patients for biopsy&#46; However&#44; this study is a standalone and there are concerns surrounding the generalizability of its results to the wider community&#46; The FUTURE trial<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> compared overall PCa and csPCa detection rates of the three Targeted Biopsy &#40;TB&#41; techniques and aimed to identify whether there was a superior technique regarding diagnostic efficacy in a repeat biopsy setting &#40;MRI-transrectal ultrasound &#40;TRUS&#41; fusion TB &#40;FUS-TB&#41;&#44; cognitive registration TRUS TB &#40;COG-TB&#41;&#44; or in-bore MRI TB &#40;MRI-TB&#41;&#46; In men with prior negative prostate biopsies and a persistent suspicion of prostate cancer&#44; the rate of CSRs &#40;PIRADS&#8239;&#8805;&#8239;3&#41; on mpMRI was 35&#37;&#46; If TB of these regions is performed&#44; the detection rate would be 49&#37; for PCa and 33&#37; for csPCa&#46; Based on this multicenter RCT&#44; there were no significant differences in the detection rates of &#40;cs&#41;PCa among the three techniques of mpMRI-based TB&#46; Consequently&#44; other factors &#40;such as local experience&#44; availability&#44; and costs&#41; should be evaluated when determining which technique&#40;s&#41; to implement&#46; Inter-reader variability remains an unsolved problem&#44; particularly when mpMRI is used in centers with little experience&#46; To overcome this issue&#44; during the past 5 years&#44; efforts have been made to implement computer- aided diagnosis &#40;CAD&#41;&#46; The aim of CAD is to bypass interobserver variability through the use of machine learning algorithms based on quantitative analyses that are able to discriminate areas within the prostate gland in which clinically significant prostate cancer is suspected&#46; Results regarding the use of CAD in mpMRI of the prostate are still preliminary&#44; but the first comparison between CAD and PI- RADS v2 showed promising results&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Current clinical practice uses mpMRI scanners with magnetic field strengths of either 1&#46;5&#8239;T or 3&#8239;T&#46; An increased signal&#58; noise ratio is provided by 3&#8239;T scanning&#44; which enables increased spatial and temporal resolution&#46; However&#44; increased field strengths might cause more artefacts&#46; Initial studies comparing 1&#46;5&#8239;T with 3&#8239;T mpMRI reported comparable accuracy in cancer localization and local staging&#46; Moreover&#44; 1&#46;5&#8239;T&#44; performed using both endorectal and surface coils&#44; seemed to show superior image quality and tumor delineation compared with 3&#8239;T&#46; Direct comparisons in homogeneous cohorts without the use of endorectal coil showed that the use of 1&#46;5&#8239;T did not compromise the diagnostic accuracy of mpMRI in terms of PI- RADS scoring&#44; achieving excellent NPV and moderate PPV &#40;94&#37; and 52&#37;&#44; respectively&#41;&#46; Furthermore&#44; no significant differences between the two field strengths were observed in a meta- analysis&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#8211;39</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">State-of-the-art full diagnostic mp-MRI of the prostate performed according to the Prostate Imaging Reporting and Data System &#40;PI-RADS&#41; v2 guidelines&#44; consists of T2- weighted imaging &#40;T2WI&#41; in three orthogonal planes&#44; and diffusion-weighted imaging &#40;DWI&#41; and dynamic contrast- enhanced &#40;DCE&#41; imaging after administration of intravenous contrast material&#46; According to the PI-RADS v2 system&#44; the role of DCE imaging is being reserved for the clarification of equivocal abnormalities in the peripheral zone&#46; The full PI-RADS-compliant protocol is&#44; however&#44; time-consuming and costly&#44; and has implementation challenges where MRI accessibility is limited&#46; This may restrict the routine use of MRI as a triage test in men with elevated PSA&#46; Van der Leest et al&#46; recently<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> have compared the diagnostic performance of monoplanar &#40;&#8220;fast&#8221; biparametric MRI &#91;bp-MRI&#93;&#41; and triplanar noncontrast bp-MRI with that of the current contrast-enhanced multiparametric MRI &#40;mp-MRI&#41; in the detection of high-grade PCa in biopsy-na&#239;ve men&#46; A prospective&#44; multireader&#44; head-to-head study included 626 biopsy-na&#239;ve men&#44; between February 2015 and February 2018&#46;They concluded Short MRI protocols can improve prostate MRI accessibility at a lower direct cost&#46; For fast bp-MRI&#44; this is at the cost of &#43;&#47;- 2&#37; more biopsies and &#43;&#47;- 1&#37; more overdetection of low-grade PCa&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Although mpMRI has been demonstrated to be a potentially cost-effective strategy pre-biopsy&#44; benefits would be amplified by improving patient selection&#46; This could be achieved by developing nomograms or by attempting to correlate biomarker results to mpMRI findings&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#44;43</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">The introduction of mpMRI as a triage test might change the traditional diagnostic pathway of prostate cancer &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Cost-effectiveness</span><p id="par0185" class="elsevierStylePara elsevierViewall">The introduction of mpMRI within the prostate cancer diagnostic pathway has advantages from a diagnostic perspective&#44; but assessing its cost- effectiveness is important&#46; One of the earliest studies addressing this topic was conducted by de Rooij et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> who developed a model based on two diagnostic strategies&#58; standard of care based on performing TRUS- guided biopsy in patients with suspected prostate cancer and an experimental mpMRI strategy based on offering mpMRI to men referred for suspected prostate cancer&#44; with subsequent mpMRI- targeted biopsy if the mpMRI is positive&#44; or routine follow- up monitoring if mpMRI is negative&#46; In both arms&#44; patients underwent active treatment &#40;radical prostatectomy or radiotherapy&#41; when clinically significant prostate cancer was diagnosed&#46; The outcomes were costs&#44; quality- adjusted life years &#40;QALYs&#41; and incremental cost- effectiveness ratios &#40;ICERs&#41;&#46; The authors concluded that&#44; although the experimental mpMRI strategy is initially more expensive &#40;expected costs of the mpMRI strategy were &#8364;31 higher than those for the TRUS- guided biopsy strategy&#41;&#44; these extra costs are compensated for by the reduction in treatment costs resulting from fewer false positives and an improved Estimation of tumor aggressiveness compared with the standard of care TRUS- guided biopsy pathway&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">43&#44;44</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions</span><p id="par0190" class="elsevierStylePara elsevierViewall">Over the past decade&#44; prostate mpMRI has been an exciting development that seems likely to change the standard prostate cancer diagnostic pathway&#46; This test is useful in a number of different patient populations and has the potential to serve as a triage test&#46; Results of studies comparing mpMRI- targeted biopsy with systematic biopsy suggest the addition of mpMRI-targeted biopsy to systematic biopsy and strategies such as mpMRI-targeted biopsy alone are feasible&#46; Use of biomarkers combined with mpMRI information can improve the performance of the mpMRI in identifying clinically significant cancer&#46; Despite the abovementioned limitations&#44; an image-based mpMRI- strategy seems to improve patient quality-of-life by reducing overdiagnosis and overtreatment at comparable to the current standard TRUSbx approach&#46;</p></span></span>"
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          "titulo" => "Introduction"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0010"
              "titulo" => "Recommendations international guidelines"
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            1 => array:2 [
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              "titulo" => "The role of imaging in clinical diagnosis &#40;mpMRI&#41;"
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            2 => array:2 [
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              "titulo" => "Clinical implications"
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            3 => array:2 [
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              "titulo" => "Future"
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              "titulo" => "Cost-effectiveness"
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          "titulo" => "Conclusions"
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        6 => array:1 [
          "titulo" => "References"
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    "fechaRecibido" => "2019-08-08"
    "fechaAceptado" => "2019-08-27"
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          "clase" => "keyword"
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          "identificador" => "xpalclavsec1226037"
          "palabras" => array:4 [
            0 => "Prostate cancer detection"
            1 => "Multiparametric magnetic resonance imaging"
            2 => "Diagnosis"
            3 => "Prostate biopsy"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1226036"
          "palabras" => array:4 [
            0 => "Detecci&#243;n de c&#225;ncer de pr&#243;stata"
            1 => "Resonancia magn&#233;tica multiparam&#233;trica"
            2 => "Diagn&#243;stico"
            3 => "Biopsia de pr&#243;stata"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Prostate cancer &#40;PCa&#41; is the second leading cause of cancer-related mortality and the most frequently diagnosed male malignant disease among men&#46; The manifestation of PCa ranges from indolent to highly aggressive disease and due to this high variation in PCa progression&#44; the diagnosis and subsequent treatment planning can be challenging&#46; The current diagnostic approach with PSA testing and digital rectal examination followed by transrectal ultrasound biopsies &#40;TRUS-bx&#41; lack in both sensitivity and specificity in PCa detection and offers limited information about the aggressiveness and stage of the cancer&#46; Scientific work supports the rapidly growing use of multiparametric magnetic resonance imaging &#40;mp-MRI&#41; as the most sensitive and specific imaging tool for detection&#44; lesion characterization and staging of Pca&#46; Therefore&#44; we carried out an updated review of Magnetic Resonance Imaging in the diagnostic prostate cancer reviewing the latest papers published in Pub Med&#46;</p></span>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El c&#225;ncer de pr&#243;stata &#40;CP&#41; es la segunda causa principal de mortalidad por c&#225;ncer y la enfermedad diagnosticada con mayor frecuencia en la poblaci&#243;n masculina&#46; El CP se manifiesta de diversas maneras&#59; desde enfermedad indolente a altamente agresiva&#46; A esto se debe la complejidad de su diagn&#243;stico y de la elecci&#243;n del tratamiento adecuado&#46; El enfoque utilizado actualmente&#44; con pruebas de PSA y examen rectal digital seguido de biopsia transrectal ecodirigida &#40;BTE&#41; carece de sensibilidad y especificidad en la detecci&#243;n de CP y ofrece informaci&#243;n limitada sobre la agresividad y el estadio del c&#225;ncer&#46; La evidencia cient&#237;fica respalda el creciente uso de la resonancia magn&#233;tica multiparam&#233;trica &#40;RMmp&#41; como la herramienta de imagen m&#225;s sensible y espec&#237;fica para la detecci&#243;n&#44; caracterizaci&#243;n de lesiones y estadificaci&#243;n del CP&#46; El presente estudio hace una revisi&#243;n actualizada del rol de la resonancia magn&#233;tica en el diagn&#243;stico de c&#225;ncer de pr&#243;stata&#44; revisando los &#250;ltimos art&#237;culos publicados en PubMed&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; &#193;lvarez-Maestro M&#46; La resonancia magn&#233;tica como herramienta para el diagn&#243;stico del c&#225;ncer de pr&#243;stata&#58; nuevas evidencias y posicionamiento de la ESUT &#40;EAU Section of Uro-Technology&#41;&#46; Actas Urol Esp&#46; 2020&#59;44&#58;148&#8211;155&#46;</p>"
      ]
    ]
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      0 => array:8 [
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        "etiqueta" => "Fig&#46; 1"
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        "figura" => array:1 [
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          0 => array:3 [
            "identificador" => "at0005"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The use of multiparametric MRI &#40;mpMRI&#41; as a triage test enables all men with negative mpMRI to be spared from receiving a biopsy&#44; opting for a surveillance strategy mainly based on the use of PSA and follow- up mpMRI&#46; &#40;For interpretation of the references to colour in this figure legend&#44; the reader is referred to the web version of this article&#41;&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\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">Study&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Precision&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">MRI-1<span class="elsevierStyleSup">st</span>&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">4&#8239;M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2019&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">Country&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UK&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">France&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Netherlands&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">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">500&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">251&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">626&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">PSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Up to 20&#8239;ng&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Up to 20&#8239;ng&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805; 3&#8239;ng&#47;mL&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">Biopsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systematic vs Target&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systematic vs Target&#8239;&#43;&#8239;Systematic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systematic vs Target&#8239;&#43;&#8239;Systematic&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">Targeting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cognitive - fusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cognitive - fusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">In bore&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">Systematic &#40;&#37;&#41;</span>ISUP 1 csPCaISUP 2 insPCa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2622&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2325&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">Target &#40;&#37;&#41;</span>ISUP 1 csPCaISUP 2 insPCa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">389&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">326&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2514&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">Patients avoiding biopsy &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18-21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Summary of precision&#44; mri-first and 4&#8239;m clinical studies &#40;csPCa&#58; significant prostate cancer&#59; insPCa&#58; insignificant prostate cancer&#41;&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:44 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Critical role of prostate biopsy mortality in the number of years of life gained and lost within a prostate cancer screening programme"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Boniol"
                            1 => "P&#46; Boyle"
                            2 => "P&#46; Autier"
                            3 => "A&#46; Ruffi"
                            4 => "P&#46; Perrin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1464-410X.2012.11513.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "BJU Int&#46;"
                        "fecha" => "2012"
                        "volumen" => "110"
                        "paginaInicial" => "1648"
                        "paginaFinal" => "1652"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22984785"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Overdiagnosis and overtreatment of prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Loeb"
                            1 => "M&#46;A&#46; Bjurlin"
                            2 => "J&#46; Nicholson"
                            3 => "T&#46;L&#46; Tammela"
                            4 => "D&#46;F&#46; Penson"
                            5 => "H&#46;B&#46; Carter"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.eururo.2013.12.062"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Urol&#46;"
                        "fecha" => "2014"
                        "volumen" => "65"
                        "paginaInicial" => "1046"
                        "paginaFinal" => "1055"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24439788"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "EAU-ESTRO-SIOG guidelines on prostate cancer&#46; Part 1&#58; screening&#44; diagnosis&#44; and local treatment with curative intent"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Mottet"
                            1 => "R&#46;C&#46;N&#46; van den Bergh"
                            2 => "E&#46; Briers"
                            3 => "P&#46; Cornford"
                            4 => "M&#46; De Santis"
                            5 => "S&#46; Fanti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "European Association of Urology Guidelines"
                        "fecha" => "2019"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnostic value of systematic biopsy methods in the investigation of prostate cancer&#58; a systematic review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:1 [
                            0 => "K&#46; Eichler"
                          ]
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0022-5347(05)00957-2"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Urol"
                        "fecha" => "2006"
                        "volumen" => "175"
                        "paginaInicial" => "1605"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16600713"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of transrectal ultrasonography &#40;TRUS&#41; in focal therapy of prostate cancer&#58; report from a Consensus Panel"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:1 [
                            0 => "M&#46; Smeenge"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1464-410X.2012.11072.x"
                      "Revista" => array:5 [
                        "tituloSerie" => "BJU Int"
                        "fecha" => "2012"
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