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The impact of time from biopsy to radical prostatectomy on Gleason score undergrading and other related factors
Impacto del tiempo desde la biopsia a la prostatectomía radical en la infragradación del grado de Gleason y análisis de factores relacionados
A.J. Virseda Rodrígueza,
Corresponding author
ajvirseda@hotmail.com

Corresponding author.
, S. Marcos Asensioa, M. Herrero Poloa, T. Hernández Sancheza, A. Sanz Ruizb, F. Garcíab, F. Vesgac, E. Gutiérrezc, J.M. Serranoc, J. Callejad, J.R. Cortiñasd, A. Zamorad, V. Rodrígueze, J.H. Amon Sesmeroe, R.J. Szczesniewskif, S. Valverde Martínezg, C. Polo Lópezg, L. Galah, F. Campanarioh, A. Barcinai..., M.A. López Aramburui, I. Moyaj, R. Bermúdezj, F. Gómez VeigaaVer más
a Servicio de Urología, Complejo Hospitalario Universitario de Salamanca, Salamanca, Spain
b Servicio de Urología, Complejo Hospitalario Universitario de León, León, Spain
c Servicio de Urología, Complejo Hospitalario Universitario de Burgos, Burgos, Spain
d Servicio de Urología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
e Servicio de Urología, Hospital Universitario Río Hortega, Valladolid, Spain
f Servicio de Urología, Hospital Santos Reyes, Aranda de Duero (Burgos), Spain
g Servicio de Urología, Hospital Nuestra Señora de Sonsoles, Ávila, Spain
h Servicio de Urología, Complejo Asistencial de Palencia, Palencia, Spain
i Servicio de Urología, Hospital Santiago Apóstol, Miranda de Ebro (Burgos), Spain
j Servicio de Urología, Complejo Asistencial de Segovia, Segovia, Spain
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Bar graph with percentages of GS of the biopsy and prostatectomy specimens&#46; A&#41; The whole sample B&#41; Less than 90 days C&#41; More than 90 days&#46; Percentages provided&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Prostate cancer &#40;PCa&#41; is the most frequent solid tumor diagnosed in adult males&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Its association with aging in a society with increased longevity and its heterogeneous biological behavior are factors that limit our ability to discriminate between tumors of low and high risk &#40;compromising patients&#8217; lives&#41; and&#44; at the same time&#44; make it fundamental&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The &#34;standard&#34; treatments for localized PCa have been radical prostatectomy &#40;RP&#41; and radiotherapy&#44; both with estimable disease control and&#47;or cure rates&#44; but with relevant side effects that may condition the quality of life of patients&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In recent years the arrival of deferred treatment &#40;active surveillance and expectant management&#41; as treatment strategy for PCa has become a reality&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It is estimated that at least 50&#37; of patients with a diagnosis of PCa could be eligible for this approach&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> One of the difficulties and criticisms of deferred strategies is fluctuating Gleason score &#40;GS&#41;&#44; with values increasing from biopsy to surgery&#44; as well as the influence of time on this tendency&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;9</span></a> Awaiting possible responses from basic &#40;biomarkers&#44; genomics&#44; etc&#46;&#44;&#41;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;12</span></a> or technological &#40;imaging&#44; diagnosis &#8230;&#41;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> research&#44; the identification and quantification of the risk of presenting Gleason score biopsy undergrading &#40;GSBU&#41; focuses in the analysis &#40;usually based on retrospective records of patients treated with RP&#41; of clinical or analytical factors of relatively easy access in usual practice that may present discriminatory capacity for this condition&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Accordingly&#44; the purpose of our study is to provide evidence of the possible impact of time from biopsy to radical prostatectomy on GSBU&#44; as well as to analyze other possible clinical and analytical factors with predictive capacity&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design and ethical considerations</span><p id="par0025" class="elsevierStylePara elsevierViewall">The data come from the RP database of the University Hospital of Salamanca and the Prostate Cancer Registry of Castilla-Le&#243;n &#40;CAPCYL&#41;&#44; collected from 2014&#44; multicenter study including public regional hospitals with PCa diagnostic and treatment capacity&#46; The data collection&#44; with more than 4000 patients on May 2019&#44; is ambispective and updated every six months&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">With the aim of complying with the new Law on Data Protection and the Standards of Good Clinical Practice&#44; the data is completed by the researchers in each center and subsequently encrypted and sent to the study coordinator for processing&#44; analysis and dissemination&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Population and criteria</span><p id="par0035" class="elsevierStylePara elsevierViewall">Data from 1955 patients treated with RP between 2005 and 2018 in 10 community healthcare centers are analyzed&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Inclusion criteria</span>&#58; patients with pathological diagnosis of localized prostate adenocarcinoma &#40;according to the DAMICO classification of PCa and the biochemical recurrence risk classification of the European Association of Urology<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#41;&#44; who had been treated with RP as first-line treatment option&#44; with GS data from before and after surgery&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Therefore&#44; patients with PCa and other histology different from adenocarcinoma&#44; and those with preoperative lower stages than locally advanced or metastatic&#44; determined by imaging tests&#44; are <span class="elsevierStyleItalic">excluded</span> from this register&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">first block</span> comprises descriptive statistics of the population characteristics with mean&#44; median and standard deviation of continuous variables and frequencies and percentages of categorical variables&#46; The preoperative and diagnostic variables included for study are year&#44; center&#44; age&#44; total&#47;free PSA&#44; PSAD&#44; neutrophil&#47;lymphocyte ratio and absolute values&#44; presence of previous prostate biopsy&#44; rectal examination and clinical stage&#44; GS&#44; ISUP<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and risk group&#46; The variables regarding outcomes or postoperative period are pathological stage&#44; GS and surgical margins&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The relationship between the biopsy GS and the RP specimen GS is categorized as agreement&#47;discrepancy&#59; the latter according to upgrading &#40;GSBUp&#41; or undergrading &#40;GSBUn&#41;&#46; The number of consecutive changes that the GS has shown is also analyzed &#40;for example&#44; a 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3 GS turning into 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4 would have a &#43;1 change and turning into 4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3 would mean a &#43;2&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The impact of time between diagnosis on biopsy and surgical procedure&#44; as well as its relationship with the GSBUn is analyzed&#46; This variable is dichotomized&#44; with a cut-off point in 90 days to facilitate its subsequent analysis&#46; Subanalysis data with time sequences of 120&#44; 150 and 180 days are also provided&#46; The Cohen&#39;s Kappa statistic is applied to test the level of agreement for each time interval&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In a <span class="elsevierStyleItalic">second block</span>&#44; inferential statistics and hypothesis testing are performed to analyze possible predictive factors of GSBUp&#46; Univariate analysis includes the Student&#39;s t and ANOVA tests for comparison of continuous variables and &#967;<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>tests for categorical variables&#46; Finally&#44; the variables considered as more clinically relevant or statistically tested as significant in the univariate analysis are selected for a multivariate analysis with binomial and multinomial logistic regression&#46; The analysis was carried out with the SPSS v&#46;25 statistical package &#40;IBM Co&#41;&#46; P values &#8804; 0&#46;05 are considered significant&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Population characteristics</span><p id="par0070" class="elsevierStylePara elsevierViewall">Out of 1955 patients&#44; 1740 89&#37;&#41; met the inclusion criteria and were eligible for the analysis&#46; The mean age was 63&#46;69 years &#40;44&#8211;80&#41; and the median PSA was 8&#46;70<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;1&#46;23&#8211;99&#41;&#46; The biochemical recurrence risk groups were distributed as follows&#58; low risk &#40;603 patients&#44; 34&#46;7&#37;&#41;&#44; intermediate &#40;856 patients&#44; 49&#46;2&#37;&#41; and high risk &#40;281 patients &#40;16&#46;1&#37;&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The biopsies were ultrasound-guided in 98&#46;7&#37; of patients&#44; transrectal and transperineal in &#40;89&#46;2&#37;&#41; and &#40;10&#46;8&#37;&#41;&#44; respectively&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The surgical access of choice was laparoscopic RP in 1388 patients 79&#46;7&#37;&#41; followed by open approach &#40;303 patients&#44; 17&#46;4&#37;&#41;&#44; and robot-assisted laparoscopic &#40;49 patients&#44; 2&#46;8&#37;&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">These data are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Agreement between pathological anatomy and grading</span><p id="par0090" class="elsevierStylePara elsevierViewall">There was agreement between the GS biopsy- specimen in 54&#46;9&#37; &#40;954 patients&#41; and discrepancy in 45&#46;1&#37; &#40;786 patients&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Data for the whole population&#46; GSBUp occurred in 180 patients &#40;10&#46;4&#37;&#41; and GSBUn in 606 patients &#40;34&#46;7&#37;&#41;&#46; Of these&#44; the most frequent &#40;442 patients&#44; 72&#46;8&#37;&#41; was downgrading of one consecutive GS degree&#46; Overall&#44; the most common GSBUp was turning from GS 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3 to GS 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4 &#40;289 patients&#44; 47&#46;6&#37;&#41; followed by GS 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4 to 4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3 &#40;117 patients&#44; 19&#46;2&#37;&#41;&#46; Data influenced by being the most frequent GS groups&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">The GSBUp is distributed disparately among the different GS of the biopsy&#44; but it has been shown that these patterns are not affected by having performed the RP before or after 90 days &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#58; it is present in 46&#37; of GS 6 patients&#44; in 31&#46;3&#37; of GS 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4&#44; in 17&#46;2&#37; of GS 4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3 patients and in 14&#46;7&#37; of GS 4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Time between biopsy and surgery</span><p id="par0100" class="elsevierStylePara elsevierViewall">The mean period of time between biopsy and surgery was 112&#46;7 days &#40;SD 69&#46;1&#41; with a minimum and maximum of 19 and 203 days&#46; The 50&#44; 75 and 90 percentiles are located in 99&#44; 141 and 182 days&#44; respectively&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">A percentage of 42&#46;9 of the patients were operated before 90 days from the biopsy&#44; and the others after three months&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">By placing the temporary cut-off point at 120&#44; 150 and 180 days&#44; there is a tendency towards greater discrepancy and GSBUp with longer periods of time between the dates of surgery and biopsy&#46; However&#44; these changes are less than 5&#37; in all cases and do not reach statistical significance &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The kappa statistic is located between 0&#46;20 and 0&#46;40 in all intervals&#44; which shows little agreement&#44; without modifications when applied to the different time intervals proposed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Relationship between downgrading and time to surgery</span><p id="par0115" class="elsevierStylePara elsevierViewall">The distribution of GSBUp among patients operated before and after 90 days did not show differences in any of the analyzed groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#44; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; and faithfully reproduces the GSBUp frequencies with respect to their mean values throughout the series&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Analysis of related factors</span><p id="par0120" class="elsevierStylePara elsevierViewall">This analysis is shown in <a class="elsevierStyleCrossRefs" href="#tbl0020">Tables 4 and 5</a>&#46; Rectal examination&#44; PSAD&#44; percentage of affected cylinders&#44; presence of bilateral tumor and GS behave as statistically significant predictors of GSBUp in the entire sample and in patients operated 90 days after the biopsy&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">Our results achieve the objective of the present work&#44; as it provides evidence on the low impact of time until surgery and GSBUp observed in our series&#46; Additionally&#44; a more detailed analysis shows that commonly accessed clinical and analytical factors are distributed differently among groups with and without GSBUp&#46;</p><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Sample characteristics and downgrading</span><p id="par0130" class="elsevierStylePara elsevierViewall">There is abundant scientific evidence about GSBUp&#46; Dinh et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> reported 44&#37; of GSBUp in their series of low-risk patients&#59; a 31&#46;3&#37; was informed by Evans et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and 30&#37; by Yang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46; However&#44; the latter only included patients with favorable intermediate risk PCa according to the NCCN guidelines &#40;PSA lower than 10&#44; less than 50&#37; positive cylinders and cT1c-cT2a digital rectal examination&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The first 2<span class="elsevierStyleHsp" style=""></span> series mentioned analyze the associated factors and perform data transformation aiming to select populations at special risk of presenting GSBUp&#46; In the first case&#44; there is a higher GSBUp related to older age&#44; percentage of affected cylinders and pathological rectal examination vs&#46; normal&#46; In the second series&#44; the time elapsed between biopsy and RP&#44; the performance of the biopsy in an urban hospital and through a transrectal approach vs&#46; transperineal&#44; showed a higher risk of presenting GSBUp&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In the efforts to identify &#171;GSBUp risk populations&#187;&#44; Porcaro et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> with only low-risk patients included&#44; reported a high GSBUp of 65&#46;3&#37;&#44; stratified patients into different populations according to PSA levels &#40;greater than or less than 5&#41; and to the rate &#40;higher or lower than 20&#37;&#41; of positive cylinders&#44; and their different possible combinations&#46; The authors conclude that the highest risk group reaches an GSBUp of 53&#46;8&#37; and the lowest group&#44; a 5&#46;1&#37;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Likewise&#44; Yang et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> once more&#44; find 2<span class="elsevierStyleHsp" style=""></span> populations differentiated by risk of GSBUp&#46; Patients with PSA 15&#8211;20 or tumor load 37&#46;5-49&#37; and PSA 15&#8211;20 present 30&#37; GSBUp&#44; as opposed to patients in cT2b-c stage and less than 12&#46;5&#37; of affected cylinders&#44; whose GSBUp risk is 10&#37; or lower&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In our series&#44; when dividing the population according to 2<span class="elsevierStyleHsp" style=""></span>of the aforementioned factors &#40;laterality and percentage of affected cylinders&#41;&#44; the group with unilateral tumor and less than 50&#37; affected cylinders presents GSBUp of 17&#46;3&#37;&#46; Regarding the group with bilateral tumor and more than 50&#37; affected cylinders&#44; the rate increases to 37&#44;1&#37;&#44; which again&#44; reproduces the behavior of other analyzed series&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">It is also interesting to identify patients and predictive factors of &#34;extreme upgrading&#34;&#44; as mentioned by Winters et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> &#40;defined as a Gleason prognostic group score increase of &#8805;2 between biopsy and specimen&#41;&#46; In their series&#44; with more than 12&#44;000 patients with GS 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3 and 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4&#44; they found 34&#37; of overall GSBUp and extreme upgrading in 6&#37; of GS 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3 patients and 4&#37; of GS 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4 &#40;11&#46;3&#37; and 9&#46;3&#37; in our series&#44; respectively&#41;&#46; Once more&#44; PSA and tumor burden were predictive factors for these results&#46; These data may be especially relevant for 2<span class="elsevierStyleHsp" style=""></span>reasons&#46; The first one&#44; in relation to the detractors of deferred strategies based on GSBUp&#46; Even though one of every 3 patients will have their GS &#8220;updated&#8221;&#44; 3 of every 4 of these updates will imply only one more score&#46; Secondly&#44; it is crucial to make particular emphasis&#44; as the authors have warned&#44; on</p><p id="par0160" class="elsevierStylePara elsevierViewall">&#8220;identifying men at greatest risk of extreme upgrading&#8221; as it &#8220;could improve patient counseling and surgical planning&#46;&#8221;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Analysis of time and other related factors</span><p id="par0165" class="elsevierStylePara elsevierViewall">In our series&#44; the time factor does not show an apparent influence on GSBUp&#46; In this regard&#44; there are heterogenous studies in the literature&#46; Although it has no impact under several authors&#8217; opinions&#44;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;7&#44;9</span></a> for Eroglu et al&#46; in their short series &#40;290 patients&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> it does&#46; In any case&#44; the work with the greatest number of patients included<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> finds a higher proportion of adverse pathological anatomy and need for rescue radiotherapy when the RP is delayed for more than 2 years&#46; However&#44; these results do not affect cancer-specific mortality&#46; These findings are reproduced by Gupta et al&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> in their series with 6000 patients and a long follow-up&#46; They also establish that the impact on the occurrence of metastases and cancer-specific mortality of low-risk groups with GSBUp and without it&#44; is scarce&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Taking these data into consideration&#44; it would be logical to think that the &#34;price&#34; of delaying RP will affect some patients&#39; pathological results or additional treatment requirements&#46; Yet&#44; these risks -especially in patients who are eligible for deferred strategies- must be globally analyzed&#44; together with the data of those patients who will avoid being overtreated&#46; Thus&#44; we must pursue an individualized risk &#40;which will never be zero&#41; and benefit assessment for each patient&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Among the numerous factors that have been investigated to increase our discriminatory capacity of patients at risk of GSBUp&#44; there are the demographic ones&#44; such as age<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and race&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> analytical&#44;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a> biopsy technique&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> pathological<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28</span></a> and those from basic research<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;12</span></a> and imaging&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> From all these&#44; and pending the development of the last 2&#44; the acknowledged factors such as PSA&#44; PSAD and those related to tumor load &#40;as well as different combinations of these&#41; are the ones that have shown better results&#46; In our series&#44; the effect of PSA&#44; PSAD and tumor laterality values &#40;in DRE and affected cylinders&#41; and the number of positive cylinders&#44; have demonstrated predictive utility of GSBUp&#46; As we have seen and mentioned previously&#44; it is expected that the best option is the use of possible combinations of these factors&#46; After all&#44; this approach is already present in the literature in an attempt to create nomograms<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> and algorithms<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> which&#44; however&#44; have not had a generalized use so far&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Applicability</span><p id="par0180" class="elsevierStylePara elsevierViewall">Our results&#44; adhered to those of other authors who have reported similar outcomes&#44; acknowledge the employment of usual clinical-analytical factors for the classification of patients by risk of presenting GSBUp&#46; Likewise&#44; communicating the limited impact of time for this condition provides evidence and tranquility for patients and urologists regarding the management of surgery waitlist times&#44; as this issue is not currently included in the clinical guidelines&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0185" class="elsevierStylePara elsevierViewall">In our series&#44; the time elapsed from biopsy and RP showed no relationship with the GSBUp pattern&#46; There are possible factors that are easily accessible in routine practice &#40;such as tumor burden&#44; laterality and PSAD&#41; that may be useful for estimating the probability of GSBUp&#46; Awaiting new tools from basic or technological research&#44; the use of these factors alone or in combination is the best way to provide individualized care to each patient&#46;</p><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Limitations</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors identify as possible limitations those inherent in the multicenter nature of the study&#44; probably implying demographic and clinical practice differences among centers &#40;which may incur bias and populations of different characteristics&#41; and the inclusion of patients in a large cohort &#40;heterogenous indications and treatment modalities&#41;&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicts of interest</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Funding</span><p id="par0200" class="elsevierStylePara elsevierViewall">The CAPCYL Registry has been supported by the SA&#47;133&#47;2014 Grant &#40;after previous approval by the Ethics Committee of the Reference center&#41;&#46;</p></span></span>"
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          "clase" => "keyword"
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            0 => "Prostate cancer"
            1 => "Undergrading"
            2 => "Gleason score"
            3 => "Delay&#46;"
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          "palabras" => array:4 [
            0 => "C&#225;ncer de pr&#243;stata"
            1 => "Ingrafradaci&#243;n"
            2 => "Grado de gleason"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Gleason score biopsy undergrading &#40;GSBU&#41; can have an impact on the management and prognosis of patients with Prostate Cancer &#40;PC&#41;&#46; We analyze the possible impact of time and other clinical and analytical factors in the appearance of GSBU in our series&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and method</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Ambispective&#44; multicenter study of 1955 patients with localized PC undergoing radical prostatectomy &#40;RP&#41; between 2005 and 2018&#46; Descriptive statistics and hypothesis testing are reported by univariate and multivariate analyses&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Mean age 63&#46;69 &#40;44&#8211;80&#41; years&#44; median PSA 8&#46;70<span class="elsevierStyleHsp" style=""></span>ng &#47; ml &#40;1&#46;23&#8211;99&#41;&#46; GSBU was observed in 34&#46;7&#37; of the entire cohort&#46; In 72&#46;8&#37; of the cases&#44; the GSBU occurred in one consecutive Gleason score&#44; with the progression from 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3 to 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4 being the most frequent &#40;289 patients&#44; 47&#46;6&#37;&#41;&#46; Performing RP 90&#8211;180 days before or after the biopsy does not have an impact on its undergrading in any of the groups&#46; In the univariate and multivariate analysis&#44; the presence of tumor or pathological rectal examination in both lobes&#44; the tumor load &#8805;50&#37; of cylinders and a DPSA<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>0&#46;20&#44; showed independent discriminative capacity to select patients who presented GSBU&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">The time from biopsy to RP did not show impact on GSBU&#46; The number of affected cylinders&#44; bilateral tumor and DPSA are easily accessible parameters that can help us select patients with greater probability of presenting GSBU&#46;</p></span>"
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            "titulo" => "Introduction"
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          1 => array:2 [
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            "titulo" => "Patients and method"
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          2 => array:2 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">La infragradaci&#243;n del Grado de Gleason de la biopsia &#40;IGGB&#41; puede impactar en el manejo y pron&#243;stico de los pacientes con C&#225;ncer de Pr&#243;stata &#40;CP&#41;&#46; Se analiza el posible impacto del tiempo y otros factores cl&#237;nico anal&#237;ticos y la aparici&#243;n de IGBB en nuestra serie&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todo</span><p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Estudio multic&#233;ntrico ambispectivo de 1955 pacientes con CP localizado sometidos a prostatectom&#237;a radical entre 2005 y 2018&#46; Se utiliza estad&#237;stica descriptiva y pruebas de contraste de hip&#243;tesis con an&#225;lisis uni y multivariados para comunicar los resultados&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">Edad media 63&#44;69 &#40;44-80&#41; a&#241;os&#44; mediana de PSA 8&#44;70<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;1&#44;23-99&#41;&#46; Se observa IGGB en el 34&#44;7&#37; de toda la muestra&#46; En el 72&#44;8&#37; de los casos la IGGB fue en un &#250;nico punto consecutivo del grado de Gleason&#44; siendo el paso de 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3 a 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4 el m&#225;s frecuente &#40;289 pacientes&#44; 47&#44;6 &#37;&#41;&#46; La realizaci&#243;n de PR antes o despu&#233;s de 90-180 d&#237;as desde la biopsia no impacto en la infragradaci&#243;n de la misma en ninguno de los grupos&#46; En el an&#225;lisis uni y multivariante la presencia de tumor o tacto rectal patol&#243;gico en ambos l&#243;bulos&#44; la carga tumoral &#8805;50&#37; de los cilindros totales y una DPSA<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>0&#46;20 mostraron capacidad discriminativa independiente para seleccionar pacientes que presentaron IGGB&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0130" class="elsevierStyleSimplePara elsevierViewall">El tiempo desde la biopsia a la PR no mostr&#243; impacto en IGGB&#46; El n&#250;mero de cilindros afectados&#44; la DPSA y presentar tumor bilateral fueron par&#225;metros de f&#225;cil acceso que pueden ayudarnos a seleccionar pacientes con mayor probabilidad de presentar IGGB&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Virseda Rodr&#237;guez A&#46;J&#46; et al&#46; Impacto del tiempo desde la biopsia a la prostatectom&#237;a radical en la infragradaci&#243;n del grado de Gleason y an&#225;lisis de factores relacionados&#46; Actas Urol Esp&#46; 2020&#59;44&#58;187&#8211;195&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Graph showing the tendency of time from biopsy to surgery&#46; A&#58; GS agreement&#59; NA&#58; No agreement&#59; GSBUn&#58; Gleason score biopsy undergrading&#59; GSBUp&#58; Gleason score biopsy upgrading&#46; Percentages and time intervals are provided with the sign -&#44; followed by days&#44; as an indicator of less than or equal to&#46;</p>"
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            "Ancho" => 3333
            "Tamanyo" => 230316
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          0 => array:3 [
            "identificador" => "at0035"
            "detalle" => "Fig&#46; "
            "rol" => "short"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Bar graph with percentages of GS of the biopsy and prostatectomy specimens&#46; A&#41; The whole sample B&#41; Less than 90 days C&#41; More than 90 days&#46; Percentages provided&#46;</p>"
        ]
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        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0040"
            "detalle" => "Table "
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">PSA&#58; prostate specific antigen&#59; ISUP&#58; International Society of Urological Pathology&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1740 patients&#46;</p>"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameter&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">Value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93; <span class="elsevierStyleBold">Demographic characteristics</span></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 " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Age &#40;years&#41;</span></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">Mean &#40;standard deviation&#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">63&#44;69 &#40;5&#44;96&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Median &#40;min-max&#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">64 &#40;44&#8211;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Center &#40;covered population&#41;</span></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">Less than 150&#44;000 n &#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">103 &#40;5&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">More than 150&#44;000 n &#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">1&#46;637 &#40;94&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#46;1&#8211;2&#93;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Year n &#40;&#37;&#41;</span></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">2005-2014&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">869 &#40;49&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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">20 15-20 19&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">871 &#40;51&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Previous biopsies n &#40;&#37;&#41;</span></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">No&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">1&#46;380 &#40;79&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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">Yes&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">360 &#40;20&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93;</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 " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93; <span class="elsevierStyleBold">Clinical characteristics</span></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 " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#46;1-2&#93;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">PSA &#40;ng&#47;ml&#41;</span></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">Mean &#40;standard deviation&#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">8&#44;7 &#40;5&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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">Median &#40;min-max&#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">7&#44;25 &#40;1&#44;23-99&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">cT n &#40;&#37;&#41;</span></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">cT1c&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">970 &#40;55&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">cT2a-b&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">614 &#40;35&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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">cT2c&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">87&#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">cT3-4&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">69 &#40;3&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cylinders removed&#44; mean &#40;SD&#41;</span></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">Total&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">10&#44;77 &#40;4&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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">Positive&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">3&#44;58 &#40;2&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Biopsy ISUP</span> n &#40;&#37;&#41;</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">1&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">834 &#40;47&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&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">527 &#40;30&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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">3&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">215 &#40;12&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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">4&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">136 &#40;7&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&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 &#40;1&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93;</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 " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93;<span class="elsevierStyleBold">Pathology results</span></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 " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ISUP &#40;specimen&#41; n &#40;&#37;&#41;</span></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">1&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
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                  \t\t\t\t">531 &#40;30&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">660 &#40;38&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">139 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">84 &#40;4&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#91;0&#44;1&#8211;2&#93;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">pT n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">pT2a-b&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
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                  \t\t\t\t">417 &#40;24&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">723 &#40;41&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">pT3a&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">462 &#40;26&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pT3b&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">121 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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">pT4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">17 &#40;0&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#46;1-2&#93;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Surgical margins n &#40;&#37;&#41;</span></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">Negative&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
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                  \t\t\t\t">1&#46;122 &#40;64&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&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">618 &#40;35&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">786 &#40;45&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Downgraded Biopsy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">606 &#40;34&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Upgraded Biopsy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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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
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                  \t\t\t\t" scope="col">GS biopsy and cohort&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\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">3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3&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">3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4&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<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3&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<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4&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">9 and 10&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 " rowspan="3" align="left" valign="middle">&#91;2&#44;0&#93;3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>834</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">&#8804;90 daysn &#61; 351&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">199 &#40;56&#44;6&#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">112 &#40;32&#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">27 &#40;7&#44;7&#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">6 &#40;1&#44;7&#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">7 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Total&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">450 &#40;54&#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"><span class="elsevierStyleBold">289 &#40;34&#44;7&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67 &#40;8&#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">16 &#40;1&#44;9&#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">12 &#40;1&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">&#62;90 daysn &#61; 483&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">258 &#40;53&#44;4&#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
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                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="middle">&#91;2&#46;0&#93; 9 and 10n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28</td><td class="td" title="\n
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                  """
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        ]
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">PSA&#58; prostate specific antigen&#59; PSAD&#58; PSA density&#59; CYL50&#37;&#58; 50 percent positive cylinders&#44; dichotomized by less&#47;equal and greater than&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Variables&#58;&#37; CYL&#58; 50<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#37; vs&#46; &#62;50&#37; positive&#46;</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">PSAD<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;20 vs&#46;<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>0&#44;20&#46;</p><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Laterality&#58; unilateral vs&#46; bilateral&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">DRE&#58;&#8804; cT2b vs<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>cT2c&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\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">Variable&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">Significance&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">OR&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">Upper limit&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">Lower limit&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 " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;5&#93; <span class="elsevierStyleItalic">Interval between biopsy and surgery &#60;90 days</span></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">Age &#40;years&#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">0&#44;40&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">1&#44;01&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">0&#44;98&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">1&#44;04&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">Continuous PSA &#40;ng&#47;ml&#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">0&#44;02&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">0&#44;22&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">1&#44;00&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">1&#44;07&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">PSAD&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">0&#44;09&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">1&#44;01&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">0&#44;99&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">1&#44;01&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">DRE&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">0&#44;42&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">0&#44;81&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">0&#44;49&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">1&#44;34&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">Laterality&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">0&#44;06&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">0&#44;71&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">0&#44;50&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">1&#44;02&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">CYL50&#37;&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">0&#44;02&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">0&#44;82&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">0&#44;19&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">0&#44;91&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 " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;5&#93;</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 " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;0&#44;1&#8211;5&#93; <span class="elsevierStyleItalic">Time interval from biopsy to surgery &#62;90 days</span></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">Age in years&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">0&#44;70&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">1&#44;00&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">0&#44;98&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">1&#44;02&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 &#40;ng&#47;ml&#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">0&#44;03&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">1&#44;02&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">1&#44;01&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">1&#44;05&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">PSAD&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">0&#44;02&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">1&#44;05&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">1&#44;04&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">1&#44;78&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">DRE&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">0&#44;05&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">0&#44;56&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">0&#44;48&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">1&#44;01&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">Laterality&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">0&#44;05&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">0&#44;76&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">0&#44;58&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">0&#44;93&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">CYL50&#37;&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">0&#44;02&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">0&#44;46&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
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Article information
ISSN: 21735786
Original language: English
DOI:10.1016/j.acuroe.2019.08.008
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