Combination of phenotype and polygenic risk score in breast cancer risk evaluation in the Spanish population: a case -control study.

BACKGROUND: In recent years, the identification of genetic and phenotypic biomarkers of cancer for prevention, early diagnosis and patient stratification has been a main objective of research in the field. Different multivariable models that use biomarkers have been proposed for the evaluation of individual risk of developing breast cancer. METHODS: This is a case control study based on a population-based cohort. We describe and evaluate a multivariable model that incorporates 92 Single-nucleotide polymorphisms (SNPs) (Supplementary Table S1) and five different phenotypic variables and which was employed in a Spanish population of 642 healthy women and 455 breast cancer patients. RESULTS: Our model allowed us to stratify two groups: high and low risk of developing breast cancer. The 9th decile included 1% of controls vs 9% of cases, with an odds ratio (OR) of 12.9 and a p-value of 3.43E-07. The first decile presented an inverse proportion: 1% of cases and 9% of controls, with an OR of 0.097 and a p-value of 1.86E-08. CONCLUSIONS: These results indicate the capacity of our multivariable model to stratify women according to their risk of developing breast cancer. The major limitation of our analysis is the small cohort size. However, despite the limitations, the results of our analysis provide proof of concept in a poorly studied population, and opens up the possibility of using this method in the routine screening of the Spanish population.

Resultados oncológicos a largo plazo del tratamiento cáncer de próstata de alto riesgo mediante prostatectomía radical en un hospital oncológico / Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital

Objetivos: Analizar los resultados oncológicos más relevantes en el tratamiento mediante prostatectomía radical (PR) en el cáncer de próstata de alto riesgo (CPAR) en un hospital oncológico. Material y métodos: Estudio retrospectivo descriptivo de las PR realizadas en nuestro centro desde 1986 a 2017 en CPAR para conocer como objetivo primario las supervivencia global (SG) y cáncer específica (SCE), y como objetivos secundarios las supervivencias libre de progresión bioquímica (SLPB), libre de progresión metastática (SLPM), la necesidad de tratamiento de rescate (SLTR), la necesidad de hormonoterapia (SLHT) y finalmente el desarrollo de cáncer de próstata resistente a la castración. Se realizan análisis de regresión de Cox para establecer modelos predictivos y conocer el peso de cada variable definitoria de alto riesgo. Resultados: Se realizaron 2.093 PR de las cuales 480 (22,9%) fueron en CPAR. La mediana de seguimiento de la serie global fue 79,57 meses (P25-75 37,92-135,16). No se realizó linfadenectomía (LDN) en el 6,5% de los casos, mientras que fue LDN obturatriz en 51,2% y extensa en 42,3%. La SG a 5, 10 y 15 años fue de 89,8% (IC 95%: 86,7-92,9%), 73,3% (IC 95%: 68-78,6%) y 51,4% (IC 95%: 43,8-59%). La SCE a 5, 10 y 15 años fue de 94,8% (IC 95%: 92,4-97,2%), 84,0% (IC 95%: 79,3-88,7%) y 75,5% (IC 95%: 68,8-82,2%) La SLPM a 5, 10 y 15 años fue de 87,4% (IC 95%: 84,1-90,7%), 72,2% (IC 95%: 66,7-77,7%) y 61,7% (IC 95%: 54,3-69,1%) respectivamente. Se requirió radioterapia de rescate en 120 pacientes de 477 analizados (25,1%) y 293/477 nunca han requerido hormonoterapia (61,4%). En relación con el uso de HT en los 93 pacientes pN1, 33 (35,5%) no la han necesitado. El tiempo desde la PR a la progresión bioquímica es la variable de mayor peso pronóstico para la SLPM, la SCE y la SG. Conclusiones: La PR más LDN extensa debería ser la primera maniobra terapéutica cuando es factible dentro de una estrategia multimodal. Es necesario un seguimiento mayor de la serie para validar la hipótesis de unos mejores resultados oncológicos basándose en una aplicación más precoz de la RT de rescate, una LDN extensa y los fármacos prolongadores de supervivencia en la fase de CPRC

Objectives: To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. Material and methods: A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. Results: A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25-75 37.92-135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7-92.9%), 73.3% (95% CI 68-78.6%) and 51.4% (95% CI 43.8-59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4-97.2%), 84.0% (95% CI 79.3-88.7%) and 75.5% (95% CI 68.8-82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1-90.7%), 72.2% (95% CI 66.7-77.7%) and 61.7% (95% CI 54.3-69.1%), respectively. A total of 120 patients of 477 analysed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. Conclusions: RP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase

Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital. / Resultados oncológicos a largo plazo del tratamiento cáncer de próstata de alto riesgo mediante prostatectomía radical en un hospital oncológico.

OBJECTIVES: To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. MATERIAL AND METHODS: A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. RESULTS: A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25-75 37.92-135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7-92.9%), 73.3% (95% CI 68-78.6%) and 51.4% (95% CI 43.8-59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4-97.2%), 84.0% (95% CI 79.3-88.7%) and 75.5% (95% CI 68.8-82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1-90.7%), 72.2% (95% CI 66.7-77.7%) and 61.7% (95% CI 54.3-69.1%), respectively. A total of 120 patients of 477 analysed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. CONCLUSIONS: RP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase.

Área maternofetal y neonatal - BCNatal / Maternal-fetal and neonatal area - BCNatal

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Estudio retrospectivo de diferentes opciones de tratamiento conservador con Bacilo de Calmette-Guèrin en el carcinoma urotelial vesical T1G3: terapia de mantenimiento / Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy

Objetivo: Comparar diferentes opciones de tratamiento conservador del tumor vesical no músculo-invasivo (TVNMI) T1 de grado alto. El bacilo de Calmette-Guérin (BCG) es el tratamiento intravesical preferido para los tumores T1 de grado alto; sin embargo, algunos expertos aún cuestionan la necesidad de la BCG de mantenimiento. Materiales y métodos: Se analizaron retrospectivamente los datos de 1.039 pacientes con TVNMI T1G3 primario y recurrente. Todos los pacientes fueron tratados mediante una resección transuretral del tumor vesical (RTUTV) completa, con músculo en la muestra y múltiples biopsias de la vejiga. Los pacientes fueron tratados con solo una RTUTV inicial (n = 108), re-RTUTV (n = 153), inducción con 27 mg de BCG (cepa Connaught) (n = 87), inducción con 81 mg de BCG (n = 489) o inducción con 81 mg de BCG + mantenimiento (n = 202). El tiempo hasta la primera recidiva, progresión (a T2 o mayor, o a enfermedad metastásica) y mortalidad específica de la enfermedad se evaluaron mediante la función de supervivencia de Kaplan-Meier y se compararon utilizando la prueba de logaritmo del rango (log-rank) y el modelo multivariado de regresión de Cox de riesgos proporcionales. Resultados: El seguimiento medio fue de 62 ± 39 meses. El riesgo de recurrencia fue significativamente menor en los pacientes tratados con terapia de mantenimiento con 81 mg de BCG que en los otros grupos de tratamiento (p < 0,001). El riesgo de progresión del tumor también fue significativamente más bajo en los pacientes tratados con mantenimiento con BCG que en los pacientes tratados solo con una RTUTV, re-RTUTV y con terapia de inducción con 27 mg de BCG (p = 0,0003). La mortalidad específica de la enfermedad fue significativamente más baja con el mantenimiento con BCG (9,4%) que con solo una RTUTV (27,8%; p = 0,003). Conclusiones: En el caso del TVNMI T1G3, la dosis completa de BCG con mantenimiento va asociada a mejores resultados de recurrencia que otras modalidades de tratamiento conservador. Los resultados de progresión y de supervivencia específica de la enfermedad también fueron mejores con la BCG de inducción, con o sin mantenimiento

Objective: To compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumours; however, a number of experts still question the need for maintenance BCG. Material and methods: We retrospectively analysed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumour (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n = 108), re-TURBT (n = 153), induction with 27 mg of BCG (Connaught strain) (n = 87), induction with 81 mg of BCG (n = 489) or induction with 81 mg of BCG + maintenance (n = 202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan-Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. Results: The mean follow-up was 62 ± 39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81 mg of BCG than in the other treatment groups (P<.001). The risk of tumour progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27 mg of BCG (P=.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; P=.003). Conclusions: In the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance

Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy. / Estudio retrospectivo de diferentes opciones de tratamiento conservador con Bacilo de Calmette-Guèrin en el carcinoma urotelial vesical T1G3: terapia de mantenimiento.

OBJECTIVE: To compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumours; however, a number of experts still question the need for maintenance BCG. MATERIAL AND METHODS: We retrospectively analysed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumour (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n=108), re-TURBT (n=153), induction with 27mg of BCG (Connaught strain) (n=87), induction with 81mg of BCG (n=489) or induction with 81mg of BCG+maintenance (n=202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan-Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. RESULTS: The mean follow-up was 62±39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81mg of BCG than in the other treatment groups (P<.001). The risk of tumour progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27mg of BCG (P=.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; P=.003). CONCLUSIONS: In the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance.

Validación externa de los ARNm: FXYD3 y KRT20 como biomarcadores predictivos de la presencia de micrometástasis en ganglios de pacientes con tumor vesical infiltrante / External validation of FXYD3 and KRT20 as predictive biomarkers for the presence of micrometastasis in muscle invasive bladder cancer lymph nodes

Introducción: Recientes estudios han propuesto que los ARNm FXYD3 y KRT20 cuantificados por qrtPCR en material parafinado podrían ser biomarcadores capaces de detectar los ganglios portadores de micrometástasis que se escapaban al análisis convencional por hematoxilina-eosina (HE). Se decidió hacer un estudio de validación en ganglios de pacientes a los que se les practicó una cistectomía radical. Objetivo: Clasificar el estado adenopático de una muestra de pacientes cistectomizados, según la expresión ganglionar de FXYD3 y KRT20. Como objetivo secundario valorar si existe una evolución oncológica diferencial de los pacientes, según la expresión ganglionar de dichas proteínas. Material y método: Se incluyeron ganglios linfáticos de 64 pacientes cistectomizados por tumor vesical infiltrante. El modelo se desarrolló a expensas de ganglios metastásicos de 15 pacientes y ganglios de 4 pacientes sin tumor conocido. La expresión génica se midió mediante PCR cuantitativa en tiempo real. Se calculó la expresión mediana mediante q-rtPCR de los ARNm de FXYD3 y KRT20 en el tejido ganglionar. Se continuó con un análisis de curvas ROC, según la función y = 0.1400 + 0.250FXYD3-2.532. Se estableció el punto de corte mediante una curva ROC. Dicha fórmula se aplicó al tejido ganglionar restante; en función del punto de corte antes establecido la muestra quedó clasificada en 4 subgrupos: HE- qrtPCR-, HE- qrtPCR+, HE+ qrtPCR+ y HE+ qrtPCR-. Se procedió a un análisis descriptivo, comparativo y a un análisis de supervivencia libre de progresión metastásica, calculando las curvas de Kaplan y Meyer para los 3 subgrupos establecidos. Los test se consideraron estadísticamente significativos cuando p < 0,05. Resultados: Mediante q-rtPCR se comprobó que había diferencias en la expresión mediana de FXYD3 (p = 0,05) y de KRT20 (p = 0,009) entre el tejido ganglionar de los pacientes con HBP y los pacientes con metástasis adenopáticas. Se asignó como punto de corte de 0,377. La muestra se clasificó en: un 37,5% de los pacientes eran pN0 por HE y pN0 por qrtPCR (-HE -qrtPCR), el 39,1% eran pN0 por HE pero eran metastásicos por qrtPCR (-HE +qrtPCR) y 15 pacientes (23,4%) eran metastásicos por ambas técnicas (+HE +qrtPCR). Las curvas de Kaplan y Meyer mostraron una peor supervivencia libre de progresión metastásica para los pacientes (+HE +qrtPCR) que para el resto de los subgrupos, no observando diferencias significativas entre (-HE +qrtPCR) y (-HE -qrtPCR). Conclusiones: Según nuestros resultados un 39,1% de los pacientes con tumor vesical infiltrante sobreexpresarían los biomarcadores FXYD3 y KRT20, siendo N0 por HE. No observamos un comportamiento clínico diferencial de los pacientes cistectomizados según su expresión de FXYD3 y KRT20 cuando son N0 por HE

Introduction: Recent studies have proposed that FXYD3 and KRT20 mRNA quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in paraffin could be biomarkers to detect lymph nodes with micrometastases that avoid detection by conventional analysis with hematoxylin-eosin (HE). A validation study was conducted on the lymph nodes of patients who underwent radical cystectomy. Objective: To classify the adenopathic state of a sample of patients who underwent cystectomy, based on the lymph node expression of FXYD3 and KRT20. The secondary objective was to assess whether there is a differential oncologic evolution for the patients, depending on the lymph node expression of these proteins. Material and method: The study included lymph nodes from 64 patients who underwent cystectomy for infiltrating bladder tumor: The model was developed using metastatic lymph nodes from 15 patients and lymph nodes from 4 patients with no known tumor. Genetic expression was measured using real-time qRT-PCR. We calculated (using qRT-PCR) the median expression of FXYD3 and KRT20 mRNA in the lymph node tissue. We then analyzed the receiver operating characteristic (ROC) curves, according to the function y = 0.1400 + 0.250FXYD3-2.532. The cutoff was established using an ROC curve. The formula was applied to the remaining lymph node tissue, based on the previously established cutoff. The sample was classified into 4 subgroups: HE- qRT-PCR-, HE- qRT-PCR+, HE+ qRT-PCR+ y HE+, qRT-PCR-. A descriptive, comparative analysis was performed, as well as a metastatic progression-free survival analysis, calculating the Kaplan and Meyer curves for the 3 established subgroups. The test results were considered statistically significant at P < .05. Results: Using qRT-PCR, we verified that there were differences in the median expression of FXYD3 (P = .05) and KRT20 (P = .009) between the lymph node tissues of patients with benign prostate hyperplasia and those of patients with lymph node metastasis. A cutoff was assigned to 0.377. The sample was classified as follows: 37.5% of the patients were pN0 by HE and pN0 by qRT-PCR (-HE -qRT-PCR), 39.1% were pN0 by HE but metastatic by qRT-PCR (-HE +qRT-PCR), and 15 patients (23.4%) were metastatic by both techniques (+HE +qRT-PCR). The Kaplan and Meyer curves showed poorer metastatic progression-free survival for the patients who were +HE and +qRT-PCR than for the other subgroups, with no significant differences between -HE +qRT-PCR and -HE -qRT-PCR. Conclusions: According to our results, 39.1% of the patients with infiltrating vesical tumors overexpressed the FXYD3 and KRT20 biomarkers and were N0 by HE. We observed no differential clinical behavior among the patients who underwent cystectomy according to their expression of FXYD3 and KRT20 when they were N0 by HE

Evaluación del dolor y factores asociados en pacientes sometidos a biopsia de próstata / Assessment and clinical factors associated with pain in patients undergoing transrectal prostate biopsy

Objetivos: Cuantificar el grado de dolor que sufren los pacientes sometidos a biopsia transrectal de próstata ecodirigida en la práctica clínica habitual, y evaluar qué factores clínicos se encuentran asociados a un mayor dolor. Material y métodos: Análisis de una serie multicéntrica de pacientes con biopsia de próstata según la práctica clínica habitual. La biopsia se realizó vía transrectal con un protocolo de anestesia local sobre el paquete nervioso posterolateral. Se evaluó el dolor a los 20 min del procedimiento a través de la escala visual analógica (0-10). Se analiza el grado de dolor soportado y se estudia la asociación de forma uni/multivariante de variables clínicas seleccionadas y el grado de dolor. Resultados: Se analizaron un total de 1.188 pacientes de 64 años de mediana de edad. Un 30% de las biopsias fueron diagnósticas de tumor. La mediana de dolor fue de 2, con un 65% de pacientes con dolor ≤ 2. El análisis multivariante muestra que el volumen prostático (RR: 1,34, IC 95%: 1,01-1,77; p = 0,04), el hecho de tener una biopsia previa (RR: 2,25, IC 95%: 1,44-3,52; p < 0,01), la edad (RR:0,63, IC 95%: 0,47-0,85; p < 0,01) y un tacto doloroso (RR: 1,95, IC 95%: 1,28-2,96; p < 0,01), son factores asociados de forma independiente con mayor dolor durante el procedimiento. Conclusiones: La biopsia transrectal con anestesia local es una técnica poco dolorosa. Factores como la edad, una biopsia previa, un tacto doloroso y el volumen prostático se asocian con la presencia de un mayor dolor durante el procedimiento

Objectives: To quantify the degree of pain experienced by patients who undergo ultrasound-guided transrectal prostate biopsy in standard clinical practice and assess the clinical factors associated with increased pain. Material and methods: Analysis of a multicenter series of patients with prostate biopsy according to standard clinical practice. The biopsy was performed transrectally with a protocol of local anesthesia on the posterolateral nerve bundle. The pain was assessed at 20 minutes into the procedure using the visual analog scale (0-10). The degree of pain was analyzed, and the association was studied using a univariate/multivariate analysis of selected clinical variables and the degree of pain. Results: A total of 1188 patients with a median age of 64 years were analyzed. Thirty percent of the biopsies were diagnosed with a tumor. The median pain score was 2, with 65% of the patients reporting a pain score ≤ 2. The multivariate analysis showed that the prostate volume (RR, 1.34; 95% CI 1.01-1.77; P = .04), having a previous biopsy (RR, 2.25; 95% CI 1.44-3.52; P < .01), age (RR, .63; 95% CI .47-.85; P < .01) and feel palpation (RR, 1.95; 95% CI 1.28-2.96; P < .01) were factors independently associated with greater pain during the procedure. Conclusions: Transrectal biopsy with local anesthesia is a relatively painless technique. Factors such as age, a previous biopsy, pain on being touched and prostate volume were associated with the presence of greater pain during the procedure

External validation of FXYD3 and KRT20 as predictive biomarkers for the presence of micrometastasis in muscle invasive bladder cancer lymph nodes.

INTRODUCTION: Recent studies have proposed that FXYD3 and KRT20 mRNA quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in paraffin could be biomarkers to detect lymph nodes with micrometastases that avoid detection by conventional analysis with hematoxylin-eosin (HE). A validation study was conducted on the lymph nodes of patients who underwent radical cystectomy. OBJECTIVE: To classify the adenopathic state of a sample of patients who underwent cystectomy, based on the lymph node expression of FXYD3 and KRT20. The secondary objective was to assess whether there is a differential oncologic evolution for the patients, depending on the lymph node expression of these proteins. MATERIAL AND METHOD: The study included lymph nodes from 64 patients who underwent cystectomy for infiltrating bladder tumor: The model was developed using metastatic lymph nodes from 15 patients and lymph nodes from 4 patients with no known tumor. Genetic expression was measured using real-time qRT-PCR. We calculated (using qRT-PCR) the median expression of FXYD3 and KRT20 mRNA in the lymph node tissue. We then analyzed the receiver operating characteristic (ROC) curves, according to the function y=0.1400+0.250FXYD3-2.532. The cutoff was established using an ROC curve. The formula was applied to the remaining lymph node tissue, based on the previously established cutoff. The sample was classified into 4 subgroups: HE- qRT-PCR-, HE- qRT-PCR+, HE+ qRT-PCR+ y HE+, qRT-PCR-. A descriptive, comparative analysis was performed, as well as a metastatic progression-free survival analysis, calculating the Kaplan and Meyer curves for the 3 established subgroups. The test results were considered statistically significant at P<.05. RESULTS: Using qRT-PCR, we verified that there were differences in the median expression of FXYD3 (P=.05) and KRT20 (P=.009) between the lymph node tissues of patients with benign prostate hyperplasia and those of patients with lymph node metastasis. A cutoff was assigned to 0.377. The sample was classified as follows: 37.5% of the patients were pN0 by HE and pN0 by qRT-PCR (-HE -qRT-PCR), 39.1% were pN0 by HE but metastatic by qRT-PCR (-HE +qRT-PCR), and 15 patients (23.4%) were metastatic by both techniques (+HE +qRT-PCR). The Kaplan and Meyer curves showed poorer metastatic progression-free survival for the patients who were +HE and +qRT-PCR than for the other subgroups, with no significant differences between -HE +qRT-PCR and -HE -qRT-PCR. CONCLUSIONS: According to our results, 39.1% of the patients with infiltrating vesical tumors overexpressed the FXYD3 and KRT20 biomarkers and were N0 by HE. We observed no differential clinical behavior among the patients who underwent cystectomy according to their expression of FXYD3 and KRT20 when they were N0 by HE.

Assessment and clinical factors associated with pain in patients undergoing transrectal prostate biopsy.

OBJECTIVES: To quantify the degree of pain experienced by patients who undergo ultrasound-guided transrectal prostate biopsy in standard clinical practice and assess the clinical factors associated with increased pain. MATERIAL AND METHODS: Analysis of a multicenter series of patients with prostate biopsy according to standard clinical practice. The biopsy was performed transrectally with a protocol of local anesthesia on the posterolateral nerve bundle. The pain was assessed at 20minutes into the procedure using the visual analog scale (0-10). The degree of pain was analyzed, and the association was studied using a univariate/multivariate analysis of selected clinical variables and the degree of pain. RESULTS: A total of 1188 patients with a median age of 64 years were analyzed. Thirty percent of the biopsies were diagnosed with a tumor. The median pain score was 2, with 65% of the patients reporting a pain score ≤2. The multivariate analysis showed that the prostate volume (RR, 1.34; 95% CI 1.01-1.77; P=.04), having a previous biopsy (RR, 2.25; 95% CI 1.44-3.52; P<.01), age (RR, .63; 95% CI .47-.85; P<.01) and feel palpation (RR, 1.95; 95% CI 1.28-2.96; P<.01) were factors independently associated with greater pain during the procedure. CONCLUSIONS: Transrectal biopsy with local anesthesia is a relatively painless technique. Factors such as age, a previous biopsy, pain on being touched and prostate volume were associated with the presence of greater pain during the procedure.

Cálculo del riesgo biológico de multirrecidiva y progresión del carcinoma urotelial no músculo-invasivo mediante nuevos modelos matemáticos / Risk estimation of multiple recurrence and progression of non muscle invasive bladder carcinoma using new mathematical models

Objetivo: El carcinoma urotelial de vejiga no músculo-invasivo (CVNMI) se caracteriza por eventos repetidos en forma de recidiva tumoral o la aparición de progresión tumoral. La aplicación del modelo de Cox para analizar estos eventos no es válido, ya que los tiempos entre recurrencias de un mismo paciente pueden estar fuertemente correlacionados, y se requiere otro tipo de modelización matemática. El objetivo del estudio es aplicar nuevos modelos matemáticos apropiados a las características biológicas del CVNMI. Material y métodos: Novecientos sesenta pacientes con diagnóstico de CVNMI con una media de seguimiento de 48,1 (3-160) meses y validación del modelo con 240 pacientes de otro centro. Se realizó resección transuretral con biopsias aleatorias. Las variables analizadas fueron: número y tamaño tumoral, edad, tratamiento adyuvante y características anatomopatológicas del tumor (grado y estadio). Para el análisis estadístico se utilizaron extensiones del modelo de Cox como el modelo de fragilidad conjunta para la multirrecidiva y progresión tumoral. Para la validación del modelo se utilizó el índice de concordancia. Resultados: Cuatrocientos sesenta y ocho (48,8%) pacientes tuvieron una recidiva tumoral y 52 (5,4%) presentaron progresión tumoral. Las variables que formaron parte del modelo para múltiple recidiva fueron la edad, el grado, el número, el tratamiento empleado y el número previo de recidivas, mientras que para progresión fueron la edad, el estadio y el grado. El índice de concordancia fue 0,64 para la multirrecidiva y 0,85 para la progresión. Conclusión: La alta concordancia obtenida y la validación con una fuente externa permite predecir con mayor precisión el riesgo de multirrecidiva y progresión

Objective: To apply new mathematical models according to Non Muscle Invasive Bladder Carcinoma (NMIBC) biological characteristics and enabling an accurate risk estimation of multiple recurrences and tumor progression. The classical Cox model is not valid for the assessment of this kind of events becausethe time betweenrecurrencesin the same patientmay be stronglycorrelated. These new models for risk estimation of recurrence/progression lead to individualized monitoring and treatment plan. Materials and methods: 960 patients with primary NMIBC were enrolled. The median follow-up was 48.1 (3-160) months. Results obtained were validated in 240 patients from other center. Transurethral resection of the bladder (TURB) and random bladder biopsy were performed. Subsequently, adjuvant localized chemotherapy was performed. The variables analyzed were: number and tumor size, age, chemotherapy and histopathology. The endpoints were time to recurrence and time to progression. Cox model and its extensions were used as joint frailty model for multiple recurrence and progression. Model accuracy was calculated using Harrell's concordance index (c-index). Results: 468 (48.8%) patients developed at least one tumor recurrence and tumor progression was reported in 52 (5.4%) patients. Variables for multiple-recurrence risk are: age, grade, number, size, treatment and the number of prior recurrences. All these together with age, stage and grade are the variables for progression risk. Concordance index was 0.64 and 0.85 for multiple recurrence and progression respectively. Conclusion: the high concordance reported besides to the validation process in external source, allow accurate multi-recurrence/progression risk estimation. As consequence, it is possible to schedule a follow-up and treatment individualized plan in new and recurrent NMCB cases

Salud ósea en pacientes con cáncer de próstata / Bone health in patients with prostate cancer

Contexto: La salud ósea se ve comprometida en los pacientes con cáncer de próstata por la avanzada edad media al diagnóstico, los tratamientos de supresión androgénica y el desarrollo de metástasis óseas. Revisamos la literatura con la finalidad de actualizar el estado del arte sobre su incidencia, prevención y manejo. Adquisición de la evidencia: Realizamos una revisión de la literatura sobre afectación ósea en los pacientes con cáncer de próstata en diferentes contextos clínicos. Síntesis de la evidencia: Los pacientes diagnosticados de cáncer de próstata experimentan una disminución de la densidad mineral ósea mayor que varones de la misma edad antes de iniciar el tratamiento. La supresión androgénica provoca una pérdida de masa ósea más intensa durante el primer año de tratamiento, y parece ralentizarse a partir de entonces, persistiendo a largo plazo. Conocer del punto de partida y de la dinámica de la pérdida de masa ósea es importante para prevenir su progresión. Los eventos relacionados con el esqueleto ejercen gran impacto en la calidad de vida de los pacientes, y tanto el denosumab como el ácido zoledrónico han demostrado ser eficaces en su reducción. Conclusiones: La prevención y el manejo de la afectación ósea en pacientes con cáncer de próstata es determinante para su calidad de vida y exige un abordaje individualizado. Antes de iniciar una supresión androgénica prolongada debe valorarse la situación de riesgo basal del hueso para adoptar las medidas protectoras apropiadas. En aquellos con metástasis debe considerarse precozmente el inicio de terapias que disminuyan el riesgo de eventos óseo

Context: In patients with prostate cancer, bone health is compromised by advanced age at diagnosis, androgen suppression treatments and the developmentofbone metastases. In this paper the medical literature is reviewed in order to update the state of the art on their incidence, prevention and management. Evidence acquisition: A literature review about bone involvement in patients with prostate cancer in different clinical settings is performed. Synthesis of the evidence: Decreased bone mineral density is higher in patients diagnosed of prostate cancer before starting treatment than in healthy men with the same age. During the first year of treatment, a severe loss bone density is reported due to androgen suppression therapy. From then on, loss bone density seems to slow down, persisting at long-term. It is important to know the starting point and the dynamics of loss bone in order to prevent its progression. The skeletal events have an important impact on quality of life in patients with prostate cancer. Both Denosumab and Zoledronic Acid have proven effective in reducing loss bone. Conclusions: The prevention and management of bone involvement in patients with prostate cancer is critical to quality of life in these patients and requires an individualized approach. Before starting a prolonged androgen deprivation, baseline risk of fracture should be evaluated in order to adopt the proper protective measures. In patients with metastases, early treatments reducing the risk of bone events should be taken into account

Información obligatoria que debe conocer un paciente con cáncer de próstata candidato a vigilancia activa / Obligatory Information that a Patient Diagnosed of Prostate Cancer and Candidate for an Active Surveillance Protocol must know

Objetivos: Conocer la información necesaria para reproducir los resultados de la literatura en vigilancia activa (VA) en cáncer de próstata (CaP) en nuestro propio centro, de tal forma que dicha información sea objetiva y se le pueda dar al paciente de forma fehaciente. Contemplamos estudiar el porcentaje de pacientes candidatos a VA y que la escogen en nuestro ambiente, los datos de infraestadificación, infragradación y predicción de CaP insignificante, depurar el poder predictivo de distintas variables clínicas para mejorar nuestros criterios de selección y analizar los resultados de nuestros pacientes en VA. Material y métodos: Revisión retro y prospectiva de nuestras bases de datos. Se analiza un periodo de un año natural seleccionando posibles candidatos a VA. Análisis de nuestras prostatectomías radicales para conocer las tasas de infraestadificación, infragradación y tasa de CaP insignificante (criterios de Epstein). Análisis uni/multivariado de variables clínicas en pacientes con tumor insignificante en pieza de prostatectomía radical. Valoración prospectiva de supervivencia global y libre de tratamiento activo (SLTA) en pacientes en VA. Resultados: Entre octubre de 2010 y octubre de 2011, un 44,7% de los CaP cumplían criterios para ser incluidos en VA, y un 11,2% la escogieron. Nuestros porcentajes de infraestadificación, infragradación y tasa de CaP insignificante fueron 14%; 31,4%; y 55,7% respectivamente, pero solo 6 pacientes (6,97%) tuvieron CaP ≥ pT3a + Gleason ≥ 7 + volumen > 0,5 cc. En el estudio multivariado para predicción de tumor insignificante, la densidad de PSA y el número de cilindros afectos son factores independientes. Con un seguimiento medio de 36 ± 39 meses, de 232 incluidos en VA, 63 pacientes pasaron a tratamiento activo (27,1%), solo 13 por ansiedad sin progresión patológica. La mediana del tiempo de SLTA es de 72,7 meses (IC 95%: 30,9-114,4). La SLTA a los 24 meses es del 76,4% (69,7-83,1%) y a 48 meses es del 58,1% (48,8-67,4%). Solo 10 pacientes (4,3%) fallecieron, 9 por causa diferente al CaP. La supervivencia global estimada a 5 años es del 92,8% (IC 95%: 86,7-98,9%). Conclusiones: El conocimiento exacto de la casuística de cada centro debería ser obligatorio para informar a los pacientes verazmente de la rentabilidad de la biopsia y de si los porcentajes de infragradación, infraestadificación y de CaP insignificante se adecuan a los de la literatura. A 3 años reproducimos los resultados de las series más longevas de VA, por lo que el programa de VA puede seguir implementándose e incluyendo cada vez a más pacientes

Objectives To know the necessary information to reproduce the results found in the literature on active surveillance (AS) in prostate cancer (PCa) in our own center so that the information would be objective and correctly given to the patients. We have aimed to study the percentage of candidates for AS chosen in our setting, and the data on infrastaging, subgrading and prediction of insignificant PCa, debugging the predictive value of clinical variables to improve our selection criteria and finally to analyze the results of our patients enrolled in AS. Materials and methods: A retro- and prospective review of our data bases was performed. A one-year period was analyzed to know AS candidates. Analysis of our radical prostatectomy specimens for infrastaging, subgrading and prediction of insignificant PCa (Epstein's criteria) was made as well as a uni/multivariate analysis of clinical variables in patients with insignificant PCa in the specimen. A prospective validation was performed with overall survival and survival free of active treatment (SFAT) as endpoints in patients enrolled in AS. Results: Between October-2010/October-2011, 44.7% of our PCa were candidates for AS, but only 11.2% choose it. The percentages found for infrastaging, subgrading and prediction of insignificant PCa were 14%, 31.4% and 55.7%, respectively. However, only just 6 patients (6.97%) had ≥ pT3a + Gleason ≥7 + volume > 0.5 cc PCa. The multivariate analysis showed that PSA density and number of affected cores were independent predictors of insignificant PCa. With a mean follow-up of 36 ± 39 months, 63 out of 232 patients enrolled in AS went on to active treatment (27.1%), with only 13 due to anxiety without pathologic progression. Median time of SFAT was 72.7 months (CI 95% 30.9-114.4). SFAT at 24 months was 76.4% (69.7-83.1%) and at 48 months 58.1% (48.8-67.4%). Only 10 patients died (4.3%), 9 due to causes different of PCa. Estimated overall survival at 5 years was 92.8% (CI 95% 86.7-98.9%). Conclusions: It should be mandatory to have the exact knowledge of the local data of each Center in order to objectively inform patients about prostate biopsy efficiency, and if percentages of infrastaging, subgrading and prediction of insignificant PCa are in accordance with the literature. At 3 years, we reproduced the results of the longest series of AS, so we have ascertained that our AS protocol can be implemented with increasingly more patients

Bone health in patients with prostate cancer.

CONTEXT: In patients with prostate cancer, bone health is compromised by advanced age at diagnosis, androgen suppression treatments and the developmentofbone metastases. In this paper the medical literature is reviewed in order to update the state of the art on their incidence, prevention and management. EVIDENCE ACQUISITION: A literature review about bone involvement in patients with prostate cancer in different clinical settings is performed. SYNTHESIS OF THE EVIDENCE: Decreased bone mineral density is higher in patients diagnosed of prostate cancer before starting treatment than in healthy men with the same age. During the first year of treatment, a severe loss bone density is reported due to androgen suppression therapy. From then on, loss bone density seems to slow down, persisting at long-term. It is important to know the starting point and the dynamics of loss bone in order to prevent its progression. The skeletal events have an important impact on quality of life in patients with prostate cancer. Both Denosumab and Zoledronic Acid have proven effective in reducing loss bone. CONCLUSIONS: The prevention and management of bone involvement in patients with prostate cancer is critical to quality of life in these patients and requires an individualized approach. Before starting a prolonged androgen deprivation, baseline risk of fracture should be evaluated in order to adopt the proper protective measures. In patients with metastases, early treatments reducing the risk of bone events should be taken into account.

Risk estimation of multiple recurrence and progression of non muscle invasive bladder carcinoma using new mathematical models.

OBJECTIVE: To apply new mathematical models according to Non Muscle Invasive Bladder Carcinoma (NMIBC) biological characteristics and enabling an accurate risk estimation of multiple recurrences and tumor progression. The classical Cox model is not valid for the assessment of this kind of events becausethe time betweenrecurrencesin the same patientmay be stronglycorrelated. These new models for risk estimation of recurrence/progression lead to individualized monitoring and treatment plan. MATERIALS AND METHODS: 960 patients with primary NMIBC were enrolled. The median follow-up was 48.1 (3-160) months. Results obtained were validated in 240 patients from other center. Transurethral resection of the bladder (TURB) and random bladder biopsy were performed. Subsequently, adjuvant localized chemotherapy was performed. The variables analyzed were: number and tumor size, age, chemotherapy and histopathology. The endpoints were time to recurrence and time to progression. Cox model and its extensions were used as joint frailty model for multiple recurrence and progression. Model accuracy was calculated using Harrell's concordance index (c-index). RESULTS: 468 (48.8%) patients developed at least one tumor recurrence and tumor progression was reported in 52 (5.4%) patients. Variables for multiple-recurrence risk are: age, grade, number, size, treatment and the number of prior recurrences. All these together with age, stage and grade are the variables for progression risk. Concordance index was 0.64 and 0.85 for multiple recurrence and progression respectively. CONCLUSION: the high concordance reported besides to the validation process in external source, allow accurate multi-recurrence/progression risk estimation. As consequence, it is possible to schedule a follow-up and treatment individualized plan in new and recurrent NMCB cases.

Influencia del número real de instilaciones de Bacilo de Calmette-Guérin aplicadas en el pronóstico de los tumores vesicales no músculo-infiltrantes / Influence of the true number of Bacillus Calmette-Guérin instillations on the prognosis of non-muscle invasive bladder tumors

Objetivos: Analizar si el número real de instilaciones de BCG aplicadas en los tumores vesicales no músculo-infiltrantes tiene alguna influencia en su pronóstico, así como otras variables clínicas y del tumor: edad, sexo, diferentes protocolos, dosis de BCG, primario o recurrente, G3 o Cis. Pacientes y métodos: De 1.491 pacientes incluidos en la base de datos del grupo CUETO se analizaron 324 tumores de alto grado (15 TaG3, 184 T1G3, 125 Cis). Tras la inducción de 6 instilaciones de BCG post-RTU fueron programados para recibir una instilación cada 2 semanas (3-6 veces), total 9-12 instilaciones. Un tercio de dosis (27 mg) en 112 casos y dosis total (81 mg) en 212 casos. Seguimiento medio: 59,6 meses. Análisis estadístico: Kaplan-Meier, regresión de Cox uni y multivariado. Resultados: Con el análisis de Kaplan-Meier y regresión de Cox multivariado se obtuvo mayor riesgo de recidiva (p = 0,032) y progresión (p = 0,013), y peor supervivencia cáncer-específica (p = 0,005) si < de 12 instilaciones. Dosis de 27 mg (p = 0,008) y el ser mujer (p < 0,001) fueron factores independientes predictivos de mayor recidiva, pero no de mayor progresión ni de peor supervivencia cáncer-específica. El resto de las características estudiadas no fueron estadísticamente significativas. Conclusiones: Con los resultados obtenidos parece que el número de instilaciones aplicadas tiene alguna influencia sobre el pronóstico, quedando por determinar cuál es el mínimo de instilaciones a partir del cual el paciente se puede beneficiar y su tiempo de aplicación. Dosis de 27 mg y el ser mujer son factores predictivos para mayor recidiva

Objectives: To analyze if the true number of BCG instillations applied in non-muscle invasive bladder tumors has any influence on their prognosis as well as other tumor and clinical characteristics: age, sex, different protocols, BCG dose, whether primary or recurrent, solitary or multiple, tumor size G3 or Cis. Patients and methods: A total of 324 high grade NMIBC (15 TaG3, 184 T1G3, 125 Cis) out of 1491 cases included in the CUETO database were analyzed. Following 6 post transurethral resection (RTU) BCG instillations, the patients were scheduled to receive one instillation every two weeks (3-6 times), for a total of 9-12 instillations. One third of the dose (27 mg) (112 cases) or total dose of 81 mg (212 cases). Mean follow-up was 59.6 months. Statistical Analysis: Kaplan-Meier, Cox-regression (uni-multivariate). Results: A higher level of recurrence (p = 0.032) and progression (p = 0.013) risk as well as worse Ca-specific survival (p = 0.005) were obtained if there were fewer than 12 instillations with the Kaplan-Meier and Cox-regression multivariate analysis. A 27 mg (p = 0.008) dosage and being a female (p < 0.001) were independent factors for a higher recurrence risk, but not for progression or Ca-specific survival. The remaining characteristics studied were not statistically significant. Conclusions: In accordance with the results obtained, we can conclude that the number of BCG instillations applied has some influence on the outcome of high grade NMIBC. The optimum number of instillations as well as their time of application must still be determined. A dose of 27 mg and being a female are predictive factors of recurrence

Optimización de un programa de cribado oportunista de cáncer de próstata; ensayo aleatorizado prospectivo del papel del PSA y del PCA3 en uso secuencial / Optimizing prostate cancer screening; prospective randomized controlled study of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening program

Objetivos: Reducir el número de biopsias (Bx) innecesarias en un programa de cribado oportunista en cáncer de próstata (CaP). Material y métodos: Estudio prospectivo y aleatorizado evaluando el PCA3 como biomarcador de segunda línea. De septiembre de 2010 a septiembre de 2012 2.366 hombres con edad en rango 40-74 años, y más de 10 años de expectativa de vida, fueron estudiados mediante PSA y tacto rectal (TR), excluyendo los biopsiados previamente o con infección urinaria reciente. Ante un TR sospechoso y/o PSA > 3 ng/ml se les realizó un PCA3. A todos aquellos con PCA3 ≥ 35 se les realizó una Bx inicial (IBx) -12 cilindros-. Con PCA3 < 35 fueron aleatorizados 1:1 a IBx u observación. Los criterios de rebiopsia (16-18 cilindros) durante el seguimiento fueron un incremento de PSA > 0,5 ng/ml a 6 meses o PSAv > 0,75 ng/ml/año. Resultados: Con un seguimiento medio de 10,1 meses se testó el PCA3 en 321/2.366 hombres (13,57%), 289 en la primera visita y 32 durante el seguimiento. Entre los 110 hombres con PCA3+ (34,3%) se identificó CaP en 43 en IBx (39,1%). En el brazo aleatorizado 110 se observaron y 101 se biopsiaron, encontrando 12 CaP (11,9%), mostrando un reducción en la detección de CaP estadísticamente significativa en esta cohorte (p < 0,001). Las tasas de detección global de CaP fueron de 40,9 y 9,5% para las ramas PCA3+ y PCA3- respectivamente (p < 0,001). AUC para PSA y PCA3 fueron 0,601 y 0,74. Este es un protocolo abierto en este momento, limitado por su seguimiento insuficiente. Conclusiones: El PCA3 como biomarcador de segunda línea en un programa de cribado oportunista podría potencialmente evitar un 65,7% de IBx y 50,1% a 10 meses de seguimiento, dejando de diagnosticar 3,2% de CaP de alto grado

Objectives: To reduce unnecessary biopsies (Bx) in an opportunistic screening programme of prostate cancer. Material and methods: We perform a prospective evaluation of PCA3 as a second line biomarker in an opportunistic screening for prostate cancer (PCa). From September-2010 until September-2012, 2,366 men, aged 40-74 years and with > 10 years life expectancy, were initially screened with PSA/digital rectal examination (DRE). Men with previous Bx or with recent urine infections were excluded. Men with abnormal DRE and/or PSA > 3 ng/ml were submitted for PCA3. All men with PCA3 ≥ 35 underwent an initial biopsy (IBx) -12 cores-. Men with PCA3 < 35 were randomized 1:1 to either IBx or observation. Re-biopsy (16-18 cores) criteria were PSA increase > 0.5 ng/ml at 4-6months or PSAv > 0.75 ng/ml/year. Results: With median follow-up (FU) of 10.1 months, PCA3 was performed in 321/2366 men (13.57%), 289 at first visit and 32 during FU. All 110 PCA3+ men (34.3%) were biopsied and PCa was identified in 43 men in IBx (39.1%). In the randomized arm, 110 were observed and 101 underwent biopsy, finding 12 PCa (11.9%), showing a statistically significant reduction of PCa detection rate in this cohort (P < 0.001). Global PCa detection rates were 40.9% and 9.5% for the PCA3+ and PCA3- branches, respectively (P < 0.001). Area under the curve for PSA and PCA3 were 0.601 and 0.74, respectively. This is an ongoing prospective study limited by its short follow-up period and still limited enrolment. Conclusions: PCA3 as a second line biomarker within an opportunistic dual screening protocol, can potentially avoid 65.7% and 50.1% biopsies at first round and at median FU of 10.1 months, respectively, just missing around 3.2% of high grade PCa

Obligatory information that a patient diagnosed of prostate cancer and candidate for an active surveillance protocol must know.

OBJECTIVES: To know the necessary information to reproduce the results found in the literature on active surveillance (AS) in prostate cancer (PCa) in our own center so that the information would be objective and correctly given to the patients. We have aimed to study the percentage of candidates for AS chosen in our setting, and the data on infrastaging, subgrading and prediction of insignificant PCa, debugging the predictive value of clinical variables to improve our selection criteria and finally to analyze the results of our patients enrolled in AS. MATERIALS AND METHODS: A retro- and prospective review of our data bases was performed. A one-year period was analyzed to know AS candidates. Analysis of our radical prostatectomy specimens for infrastaging, subgrading and prediction of insignificant PCa (Epstein's criteria) was made as well as a uni/multivariate analysis of clinical variables in patients with insignificant PCa in the specimen. A prospective validation was performed with overall survival and survival free of active treatment (SFAT) as endpoints in patients enrolled in AS. RESULTS: Between October-2010/October-2011, 44.7% of our PCa were candidates for AS, but only 11.2% choose it. The percentages found for infrastaging, subgrading and prediction of insignificant PCa were 14%, 31.4% and 55.7%, respectively. However, only just 6 patients (6.97%) had≥pT3a+Gleason≥7+volume>0.5cc PCa. The multivariate analysis showed that PSA density and number of affected cores were independent predictors of insignificant PCa. With a mean follow-up of 36±39months, 63 out of 232 patients enrolled in AS went on to active treatment (27.1%), with only 13 due to anxiety without pathologic progression. Median time of SFAT was 72.7 months (CI 95% 30.9-114.4). SFAT at 24 months was 76.4% (69.7-83.1%) and at 48 months 58.1% (48.8-67.4%). Only 10 patients died (4.3%), 9 due to causes different of PCa. Estimated overall survival at 5 years was 92.8% (CI 95% 86.7-98.9%). CONCLUSIONS: It should be mandatory to have the exact knowledge of the local data of each Center in order to objectively inform patients about prostate biopsy efficiency, and if percentages of infrastaging, subgrading and prediction of insignificant PCa are in accordance with the literature. At 3 years, we reproduced the results of the longest series of AS, so we have ascertained that our AS protocol can be implemented with increasingly more patients.

Influence of the true number of Bacillus Calmette-Guérin instillations on the prognosis of non-muscle invasive bladder tumors.

OBJECTIVES: To analyze if the true number of BCG instillations applied in non-muscle invasive bladder tumors has any influence on their prognosis as well as other tumor and clinical characteristics: age, sex, different protocols, BCG dose, whether primary or recurrent, solitary or multiple, tumor size G3 or Cis. PATIENTS AND METHODS: A total of 324 high grade NMIBC (15 TaG3, 184 T1G3, 125 Cis) out of 1491 cases included in the CUETO database were analyzed. Following 6 post transurethral resection (RTU) BCG instillations, the patients were scheduled to receive one instillation every two weeks (3-6 times), for a total of 9-12 instillations. One third of the dose (27 mg) (112 cases) or total dose of 81 mg (212 cases). Mean follow-up was 59.6 months. Statistical Analysis: Kaplan-Meier, Cox-regression (uni-multivariate). RESULTS: A higher level of recurrence (p = 0.032) and progression (P = .013) risk as well as worse Ca-specific survival (P = .005) were obtained if there were fewer than 12 instillations with the Kaplan-Meier and Cox-regression multivariate analysis. A 27 mg (P = .008) dosage and being a female (P < .001) were independent factors for a higher recurrence risk, but not for progression or Ca-specific survival. The remaining characteristics studied were not statistically significant. CONCLUSIONS: In accordance with the results obtained, we can conclude that the number of BCG instillations applied has some influence on the outcome of high grade NMIBC. The optimum number of instillations as well as their time of application must still be determined. A dose of 27 mg and being a female are predictive factors of recurrence.

La prostatectomía radical es un tratamiento razonable para los pacientes mayores de 70 años / Radical Prostatectomy is a Reasonable Treatment for Patients Over 70 Years of Age

Objetivo: Comparar la naturaleza tumoral y la evolución oncológica de los pacientes intervenidos mediante prostatectomía radical en 3 grupos de edad. Material y método: De la base de datos de cumplimentación prospectiva de nuestro Servicio, analizamos 1.012 pacientes intervenidos entre los años 1986 y diciembre de 2009. Se excluyeron los pacientes con tratamiento neo o adyuvante y aquellos con PSA preoperatorio mayor de 50. Se dividió la muestra en 3 grupos: menores de 60, de 61 a 69 y los de 70 y mayores. Se analizaron las variables clínicas, patológicas, la evolución bioquímica y la necesidad de rescate. Consideramos recidiva bioquímica cuando los valores de PSA alcanzan cifras mayores de 0,4 en 2 mediciones consecutivas. Se definió rescate como la necesidad de tratamiento hormonal o de la administración de radioterapia. Procedimos a un estudio comparativo, un análisis de supervivencia univariante mediante curvas de Kaplan y Meyer y multivariante mediante regresión de Cox. Resultados: La mediana de seguimiento fue de 55,1 meses. De los 1.012 pacientes incluidos en el estudio 317 pacientes (31,3%) experimentaron progresión bioquímica y 259 (25,6%) necesitaron rescate. Observamos que los grupos de mayor edad tenían un PSA significativamente más alto y mayores estadios que el resto. No se objetivaron diferencias en el Gleason de la pieza quirúrgica ni en el estado de los márgenes quirúrgicos. La supervivencia libre de recidiva bioquímica a los 5 años fue del 72,3% (IC 95%: 66,4-78,2) en los pacientes menores de 60 años, del 65,3% (IC 95%: 60,6-70,0) para los pacientes menores de 70 y del 62,2% (IC 95%: 53,2-71,1) para los pacientes con 70 o más años; p < 0,05. En el estudio univariante la edad fue un factor que se asoció significativamente a la recidiva bioquímica; sin embargo, en el estudio multivariante pierde su interés y lo cobrabá el PSA, el estado patológico y el Gleason. La supervivencia libre de rescate no difería por grupos de edad. Conclusiones: En el presente estudio se objetivó una peor evolución bioquímica de los pacientes mayores de 70 años, sin embargo esta peor evolución bioquímica estuvo condicionada por tumores clínicamente más agresivos, lo que a nuestro juicio justifica la decisión tomada en cuanto a la actitud quirúrgica para con estos pacientes

Objective: To compare the tumor nature and oncological course of patients operated on by radical prostatectomy in three age groups. Materials and methods: From the prospective completion of the data base of our department, we analyzed 1012 patients operated on between 1986 and December 2009. Patients with neo- or adjuvant treatment and those with pre-operative PSA over 50 were excluded. The sample was divided into three groups: younger than 60, 60-69 and over 70. The clinical, pathological variables, biochemical course and need for rescue treatment were analyzed. We consider biochemical relapse as when the PSA values reached values greater than 0.4 in two consecutive measurements. Rescue was defined as the need for hormone treatment or radiotherapy. We then made a comparative study, a univariate survival analysis by Kaplan and Meyer Curves and multivariate by Cox's regression. Results: The median follow-up was 55.1 months. Of the 1012 patients included in the study, 317 patients (31.3%) had biochemical progression and 259 (25.6%) required rescue treatment. We observed that the groups with the older age had a significantly higher PSA and higher stages than the rest. No differences were observed in the Gleason score of the surgical specimen or in the state of the surgical margins. Biochemical relapse free survival at 5 years was 72.3% (CI 66.4-78.2) in patients under 60 years, 65.3% (CI 60.6-70.0) for patients under 70 and 62.2% (CI 53.2-71.1) for patients of 70 years or older; P < 0.05. In the univariate study, age was a factor that was significantly associated to biochemical relapse. However, it loses interest in the multivariate study and PSA, pathological state and Gleason score regain interest. Rescue treatment free survival did not differ by age groups. Conclusions: In the current study, worse biochemical evolution of patients over 70 was observed. However, this worse biochemical course was conditioned by clinically more aggressive tumors that, in our opinion, justifies the decision made in regards to the surgical approach taken with these patients