Biomarkers for characterization and therapeutic orientation in castration-resistant prostate cancer. / Biomarcadores para la caracterización y orientación terapéutica en Cáncer de Próstata Resistente a la Castración (CPRC).

Whole exome sequencing studies haverevealed the molecular landscape of metastatic CastrateResistant Prostate Cancer (mCRPC) providingnew information about prognostic and predictive factorsof response to therapies. These studies highlightedpotentially actionable targets leading to the beginingof the biomarker-driven era in prostate cancer.Alterations in androgen receptor (AR), DNA repair genes,PI3K-AKT-MTOR pathway or in genes involved incell cycle are frequently observed in mCRPC patientsand may be relevant in the resistance induced mechanismto approve therapy in this setting. Poly(ADP-ribose)polymerase (PARP) inhibitor in BRCA mutatedpatients, pembrolizumab (inmune checkpoint inhibitors)in mCRPC patients with mismatch repair genedefects and microsatellite instability and ipatasertib(AKT inhibitor) in patients with loss of function inPTEN are examples on how molecular information canbe useful to improve treatment selection. Nonethelessthe heterogeneity of advanced PC, the lack of consensusregarding the optimal biological source of analysisand the optimal time and technique for the analisysare still challenges that need to be defined in the nextfuture. The aim is to review the current literature concerningprognostic and predictive marker of responseto therapies in the mCRPC setting.

Estudios de secuenciación completa delexoma han revelado el perfil molecular del pacientecon Cáncer de Próstata Resistente a la Castración metastásico(CPRCm) proporcionando nueva informaciónsobre factores pronósticos y predictivos de respuestaa las distintas alternativas terapéuticas. Muchos deestos estudios han resaltado numerosas dianas molecularesaccionables desde un punto de vista farmacológico,conduciéndonos al comienzo de la medicina deprecisión en el Cáncer de Próstata (CP). Alteracionesen el Receptor de Andrógenos (RA), en genes reparadoresde DNA, en la vía de PI3K-AKT-MTOR o en genesimplicados en el ciclo celular son frecuentementeobservadas en CPRCm y pueden ser relevantes en la selección terapéutica y en la comprensión de los mecanismosde resistencia.Los inhibidores de la poli (ADP-ribosa) polimerasaen pacientes con mutaciones en BRCA, pembrolizumab(inhibidor de los puntos de control inmunológico)en pacientes CPRCm con alteraciones en genesimplicados en el "mismatch repair" o inestabilidad demicrosatélites e ipatasertib (inhibidor de AKT) en pacientescon pérdida de función de PTEN son ejemplosde cómo la información molecular puede ser útil paraoptimizar la selección terapéutica en este escenario.No obstante, la heterogeneidad del CP avanzado, lafalta de consenso sobre la fuente biológica óptima parael análisis, el momento y la técnica de análisis continúansiendo desafíos a definir en un fututo próximo.El objetivo es revisar la literatura actual sobre marcadorespronósticos y predictivos de respuesta a tratamientoen el entorno del CPRCm.

Biomarcadores para la caracterización y orientación terapéutica en cáncer de próstata resistente a la castración (cprc) / Biomarkers for characterization and therapeutic orientation in castration-resistant prostate cáncer

- Estudios de secuenciación completa delexoma han revelado el perfil molecular del pacientecon Cáncer de Próstata Resistente a la Castración metastásico (CPRCm) proporcionando nueva informaciónsobre factores pronósticos y predictivos de respuestaa las distintas alternativas terapéuticas. Muchos deestos estudios han resaltado numerosas dianas moleculares accionables desde un punto de vista farmacológico, conduciéndonos al comienzo de la medicina deprecisión en el Cáncer de Próstata (CP). Alteracionesen el Receptor de Andrógenos (RA), en genes reparadores de DNA, en la vía de PI3K-AKT-MTOR o en genes implicados en el ciclo celular son frecuentementeobservadas en CPRCm y pueden ser relevantes en la selección terapéutica y en la comprensión de los mecanismos de resistencia.Los inhibidores de la poli (ADP-ribosa) polimerasaen pacientes con mutaciones en BRCA, pembrolizumab (inhibidor de los puntos de control inmunológico) en pacientes CPRCm con alteraciones en genesimplicados en el “mismatch repair” o inestabilidad demicrosatélites e ipatasertib (inhibidor de AKT) en pacientes con pérdida de función de PTEN son ejemplosde cómo la información molecular puede ser útil paraoptimizar la selección terapéutica en este escenario.No obstante, la heterogeneidad del CP avanzado, lafalta de consenso sobre la fuente biológica óptima parael análisis, el momento y la técnica de análisis continúan siendo desafíos a definir en un fututo próximo.El objetivo es revisar la literatura actual sobre marcadores pronósticos y predictivos de respuesta a tratamiento en el entorno del CPRCm. (AU)

Whole exome sequencing studies haverevealed the molecular landscape of metastatic Castrate Resistant Prostate Cancer (mCRPC) providingnew information about prognostic and predictive factors of response to therapies. These studies highlighted potentially actionable targets leading to the begining of the biomarker-driven era in prostate cancer.Alterations in androgen receptor (AR), DNA repair genes, PI3K-AKT-MTOR pathway or in genes involved incell cycle are frequently observed in mCRPC patientsand may be relevant in the resistance induced mechanism to approve therapy in this setting. Poly(ADP-ribose) polymerase (PARP) inhibitor in BRCA mutatedpatients, pembrolizumab (inmune checkpoint inhibitors) in mCRPC patients with mismatch repair genedefects and microsatellite instability and ipatasertib (AKT inhibitor) in patients with loss of function inPTEN are examples on how molecular information canbe useful to improve treatment selection. Nonethelessthe heterogeneity of advanced PC, the lack of consensus regarding the optimal biological source of analysisand the optimal time and technique for the analisysare still challenges that need to be defined in the nextfuture. The aim is to review the current literature concerning prognostic and predictive marker of responseto therapies in the mCRPC setting. (AU)

Adrenal lipoma: A case report and literature review.

The study reports a case of a 57-year-old female patient with incidental right adrenal lipoma (LA). The tumor was detected by ultrasound (US) and confirmed by computed tomography (CT). Due to the size of the mass, it was decided to perform a laparoscopic adrenalectomy. During the differential microscopic diagnosis, were considered adrenal lipomatous tumors, myelolipoma, angiomyolipoma and teratomas, among others. In all these neoplasms, LA is a rare tumor, with only 24 cases reported in the anglo-saxon literature revised. It is a benign adrenal gland tumor with generally asymptomatic and non-functioning nature.

Pathological findings in very low risk prostate cancer in surgical specimens. / Hallazgos patológicos en el cáncer de próstata de muy bajo riesgo en piezas de prostatectomía radical.

OBJECTIVE: Perform a detailed anatomopathological analysis of consecutive surgical specimens in men with clinically very low risk prostate cancer according to National Comprehensive Cancer Network (NCCN) criteria.MATERIALS AND METHODS: The study included 799 prostate cancer patients who under went radical prostatectomy between January 2005 and December 2013. We identified 81 consecutive patients with clinically very low risk prostate cancer. The slides of the patients who fulfilled the inclusion criteria were re-reviewed. The parameters studied were: pathological stage, histological grade by Gleason score (GSS), margins involvement, tumor percentage (PT), and number of apparently independent tumor foci (FT). RESULTS: The patients had organ-confined tumors in almost all of them (pT2: 97.5%). Most of the cancers studied were bilateral (pT2c: 67.9%), multifocal (FT≥2:88.8%), with a low tumor percentage (PTand with a low Gleason Score (GSS≤6: 91,3%). Non-confined disease: 2.5%, all cases extra-prostatic extension (pT3a). GSS>6: 8,6%, all cases GSS7 (3+4). CONCLUSIONS: The NCCN criteria for very low risk prostate cancer help to make a good selection of non-aggressive tumors and are a useful tool for including patients in an active surveillance program.

OBJETIVO: Realizar un análisis patológic odetallado de las piezas de prostatectomía radical en pacientes diagnosticados con cáncer de próstata de muy bajo riesgo según los criterios de la NCCN. MATERIAL Y MÉTODOS: El estudio incluye 799 pacientes con cáncer de próstata a los que se realizó una prostatectomía radical entre 2005 y 2013. 81 pacientes con cáncer de próstata clínicamente de muy bajo riesgo fueron identificados. Las laminillas de los pacientes identificados fueron revisadas. Los parámetros estudiados fueron: estadio patológico, grado de Gleason, márgenes quirúrgicos, % de tumor, y el numero de focos tumorales aparentemente independientes. RESULTADOS: La gran mayoría de pacientes presentaron tumores órgano-confinados (pT2: 97,5%). El 68% de los canceres fue bilateral (pT2c), multifocal (mas de2 focos 88%), con un porcentaje tumoral de menos del 10% en el 80% de los casos y mas del 90% con Gleason 6. La enfermedad no órgano-confinada se evidencio en 2,5% pT3a. CONCLUSIONES: Los criterios de NCCN para muy bajo riesgo nos ayudan a clasificar pacientes con tumores poco agresivos y son una buena herramienta para seleccionar pacientes para programas de vigilancia activa.

Hallazgos patológicos en el cáncer de próstata de muy bajo riesgo en piezas de prostatectomía radical / Pathological findings in very low risk prostate cancer in surgical specimens

OBJETIVO: Realizar un análisis patológico detallado de las piezas de prostatectomía radical en pacientes diagnosticados con cáncer de próstata de muy bajo riesgo según los criterios de la NCCN. MATERIAL Y MÉTODOS: El estudio incluye 799 pacientes con cáncer de próstata a los que se realizó una prostatectomía radical entre 2005 y 2013. 81 pacientes con cáncer de próstata clínicamente de muy bajo riesgo fueron identificados. Las laminillas de los pacientes identificados fueron revisadas. Los parámetros estudiados fueron: estadio patológico, grado de Gleason, márgenes quirúrgicos, % de tumor, y el numero de focos tumorales aparentemente independientes. RESULTADOS: La gran mayoría de pacientes presentaron tumores órgano-confinados (pT2: 97,5%). El 68% de los canceres fue bilateral (pT2c), multifocal (mas de 2 focos 88%), con un porcentaje tumoral de menos del 10% en el 80% de los casos y mas del 90% con Gleason 6. La enfermedad no órgano-confinada se evidencio en 2,5% pT3a. CONCLUSIONES: Los criterios de NCCN para muy bajo riesgo nos ayudan a clasificar pacientes con tumores poco agresivos y son una buena herramienta para seleccionar pacientes para programas de vigilancia activa

OBJECTIVE: Perform a detailed anatomopathological analysis of consecutive surgical specimens in men with clinically very low risk prostate cancer according to National Comprehensive Cancer Network (NCCN) criteria. MATERIALS AND METHODS: The study included 799 prostate cancer patients who underwent radical prostatectomy between January 2005 and December 2013. We identified 81 consecutive patients with clinically very low risk prostate cancer. The slides of the patients who fulfilled the inclusion criteria were re-reviewed. The parameters studied were: pathological stage, histological grade by Gleason score (GSS), margins involvement, tumor percentage (PT), and number of apparently independent tumor foci (FT). RESULTS: The patients had organ-confined tumors in almost all of them (pT2: 97.5%). Most of the cancers studied were bilateral (pT2c: 67.9%), multifocal (FT≥2: 88.8%), with a low tumor percentage (PT<10%: 80.2%) and with a low Gleason Score (GSS≤6: 91,3%). Non-confined disease: 2.5%, all cases extra-prostatic extension (pT3a). GSS>6: 8,6%, all cases GSS7(3+4). CONCLUSIONS: The NCCN criteria for very low risk prostate cancer help to make a good selection of non-aggressive tumors and are a useful tool for including patients in an active surveillance program

Prostate cancer epidemiology.

OBJECTIVES: The aim of this study is to provide an evidence-based analysis of the epidemiological situation of prostate cancer today and its future perspectives. METHOD: A literature review on Medline has been made of the most relevant papers related to the epidemiology of prostate cancer and their etiological factors. We selected for review those manuscripts with the highest level of evidence. RESULTS: Prostate cancer is the second most common neoplasia in men worldwide. The increasing trend in the incidente counteracted by an overall decrease in mortality from this disease have made prostate cancer an important health problem because of its high prevalence. There are significant geographic differences in terms of incidence and mortality. Age, ethnicity and family history are risk factors demonstrated but there are other factors related to the environment that play an important role in the biology of prostate cancer and tumor genesis. CONCLUSIONS: In the last 20 years there has been a progressive increase in the global incidence of this disease probably secondary to a progressive aging population, the improvement in diagnostic techniques and a higher intensity screening of prostate cancer. Though mortality has been reduced prostate cancer is the sixth cause of cancer-specific death worldwide. The combination of genetic and environmental factors may explain the ethnic and geographical variations in the incidence and mortality from prostate cancer.

Epidemiología del cáncer de próstata / Prostate cancer epidemiology

OBJETIVO: El objetivo del presente trabajo es ofrecer un análisis basado en la evidencia de la situación epidemiológica del cáncer de próstata en la actualidad y sus perspectivas futuras. MÉTODO: Se ha realizado una revisión bibliográfica en Medline de los trabajos más relevantes referidos a la epidemiología del cáncer de próstata y a sus factores etiológicos. Se seleccionaron para revisión aquellos manuscritos con mayor nivel de evidencia. RESULTADOS: El cáncer de próstata es la segunda neoplasia más frecuente en hombres a nivel mundial. La tendencia incremental de la incidencia contrarrestada con un descenso global en la mortalidad por esta patología hacen del cáncer de próstata un importante problema de salud debido a su elevada prevalencia. Existen importantes diferencias geográficas tanto en relación a la incidencia como a la mortalidad. La edad, la etnia y los antecedentes familiares son factores de riesgo demostrados pero existen también otros factores relacionados con el entorno que también juegan un papel importante en la biología del cáncer de próstata y en la génesis tumoral. CONCLUSIÓN: En los últimos 20 años se ha producido un incremento progresivo en la incidencia mundial de esta patología, probablemente secundaria a un progresivo envejecimiento poblacional, a la mejora en las técnicas diagnósticas y a una mayor intensidad de cribado de esta patología. A pesar de que la mortalidad se ha reducido, el cáncer de próstata es la sexta causa de muerte cáncer-específica a nivel mundial. La combinación de factores genéticos y ambientales podría explicar las variaciones étnicas y geográficas en cuanto a las tasas de incidencia y mortalidad por cáncer de próstata

OBJECTIVES: The aim of this study is to provide an evidence-based analysis of the epidemiological situation of prostate cancer today and its future perspectives. METHOD: A literature review on Medline has been made of the most relevant papers related to the epidemiology of prostate cancer and their etiological factors. We selected for review those manuscripts with the highest level of evidence. RESULTS: Prostate cancer is the second most common neoplasia in men worldwide. The increasing trend in the incidente counteracted by an overall decrease in an important health problem because of its high prevalence. There are significant geographic differences in terms of incidence and mortality. Age, ethnicity and family history are risk factors demonstrated but there are other factors related to the environment that play an important role in the biology of prostate cancer and tumor genesis. CONCLUSIONS: In the last 20 years there has been a progressive increase in the global incidence of this disease probably secondary to a progressive aging population, the improvement in diagnostic techniques and a higher intensity screening of prostate cancer. Though mortality has been reduced prostate cancer is the sixth cause of cancer-specific death worldwide. The combination of genetic and environmental factors may explain the ethnic and geographical variations in the incidence and mortality from prostate cancer

Bladder cancer in Spain 2011: population based study.

PURPOSE: We estimate the annual incidence of bladder cancer in Spain and describe the clinical profile of patients with bladder cancer enrolled in a population based study. MATERIALS AND METHODS: Using the structure of the Spanish National Health System as a basis, in 2011 the AEU (Spanish Association of Urology) conducted this study with a representative sample from 26 public hospitals and a reference population of 10,146,534 inhabitants, comprising 21.5% of the Spanish population. RESULTS: A total of 4,285 episodes of bladder cancer were diagnosed, of which 2,476 (57.8%) were new cases and 1,809 (42.2%) were cases of recurrence, representing an estimated 11,539 new diagnoses annually in Spain. The incidence of bladder cancer in Spain, age adjusted to the standard European population, was 20.08 cases per 100,000 inhabitants (95% CI 13.9, 26.3). Of patients diagnosed with a first episode of bladder cancer 84.3% were male, generally older than 59 years (81.7%) with a mean ± SD age of 70.5 ± 11.4 years. Of these patients 87.5% presented with some type of clinical symptom, with macroscopic hematuria (90.8%) being the most commonly detected. The majority of primary tumors were nonmuscle invasive (76.7%) but included a high proportion of high grade tumors (43.7%). According to the ISUP (International Society of Urologic Pathology)/WHO (2004) classification 51.1% was papillary high grade carcinoma. Carcinoma in situ was found in 2.2% of primary and 5.8% of recurrent cases. CONCLUSIONS: The incidence of bladder cancer in Spain, age adjusted to the standard European population, confirms that Spain has one of the highest incidences in Europe. Most primary nonmuscle invasive bladder cancer corresponded to high risk patients but with a low detected incidence of carcinoma in situ.