Outcomes and patterns of use of Radium-223 in metastatic castration-resistant prostate cancer.

Introduction: Radium-223 dichloride (Ra-223) is recommended as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic bone metastases and no visceral disease, after docetaxel failure, or in patients who are not candidates to receive it. In this study, we aimed to ambispectively analyze overall survival (OS) and prognostic features in mCRPC in patients receiving Ra-223 as per clinical routine practice and identify the most suitable treatment sequence. Patients and methods: This study is observational, multicentric, and ambispective. Eligibility criteria included mCRPC patients treated with Ra-223, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, without visceral metastases, and no more than three cm involved lymph nodes. Results: A total of 145 patients were included; the median age was 73.97 years, and a Gleason score of more than or equal to 7 in 61 (48%) patients; 73 (81%) had previously received docetaxel. The most important benefit was reached by those patients who received Ra-223 in the second-line setting, with a median OS of 17 months (95% CI, 12-21), and by patients who received six cycles of treatment, with a median OS of 19 months (95% CI, 14-21). An alkaline phosphatase (ALP) decrease was also identified as a prognosis marker. When performing the multivariate analysis, the time to develop castration-resistant disease longer than 24 months was the most important prognostic factor to predict the evolution of the patients receiving Ra-223. Ra-223 was well tolerated, with thrombocytopenia, anemia, and diarrhea being the main adverse events. Conclusion: There is a benefit for those patients who received Ra-223 in the second-line setting, regardless of prior use of docetaxel. In addition, a survival benefit for patients presenting with a decline in ALP was observed.

[Advanced prostate cancer and quality of life.] / Cáncer de próstata avanzado y calidad de vida.

OBJECTIVES: The therapeutic range in advanced and castration resistant prostate cancer is widening. Therapies must offer real clinical efficacy, and they also should be acceptable and desirable for patients, specially in advanced disease. We analyze the value of quality of life analysis in patients with advanced prostate cancer. METHODS: We performed a bibliographic review (Pubmed) with the various health related quality of life scales available and different clinical trials on advanced prostate cancer. RESULTS: There are numerous therapeutic options but, due to variations in study design, a different evaluation of adverse events and different therapeutic regimens, comparisons are difficult. A common method to interpret results is not available, so most of the times that interpretation is left to statistical significance, which is not always well correlated with clinical significance. CONCLUSIONS: To propose the most adequate treatment in patient`s interest, we need results focused on patients that combine not only quantity or overall survival but also quality of life. Parameters such as QALY should be included in clinical trials as evaluation objectives in order to favor decision taking.

Cáncer de próstata avanzado y calidad de vida / Advanced prostate cancer and quality of life

OBJETIVOS: El abanico terapéutico en cáncer de próstata avanzado y resistente a castración es cada vez mayor. Los tratamientos deben ofrecer una eficacia clínica real, pero también, especialmente en enfermedades avanzadas deben ser aceptables deseables para los pacientes. En el presente trabajo analizamos el valor del análisis de calidad de vida en paciente con cáncer de próstata avanzado. MÉTODOS: Realizamos una revisión de la literatura disponible -pubmed- con las distintas escalas de calidad de vida relacionada con la salud y los distintitos ensayos clínicos en cáncer de próstata avanzado. RESULTADOS: Existen numerosas opciones terapéuticas pero debido a la variación en los diseños de los estudios, distinta valoración de los efectos adversos y distintos régimenes de tratamiento la comparación entre ellos es difícil, no se dispone de un método común para interpretar resultados, por lo que la mayor parte de la veces esa interpretación se deja a la significación estadística, no siempre bien correlacionada con la significación clínica. CONCLUSIONES: Necesitamos resultados centrados en el paciente que combinen no sólo cantidad o supervivencia global sino también calidad de vida para proponer el tratamiento más adecuado en interés del paciente. Los parámetros como los AVACS deberían ser incluidos como objetivos de valoración en los ensayos clínicos para favorecer la toma de decisiones

OBJECTIVES: The therapeutic range in advanced and castration resistant prostate cancer is widening. Therapies must offer real clinical efficacy, and they also should be acceptable and desirable for patients, specially in advanced disease. We analyze the value of quality of life analysis in patients with advanced prostate cancer. METHODS: We performed a bibliographic review (Pubmed) with the various health related quality of life scales available and different clinical trials on advanced prostate cáncer. RESULTS: There are numerous therapeutic options but, due to variations in study design, a different evaluation of adverse events and different therapeutic regimens, comparisons are difficult. A common method to interpret results is not available, so most of the times that interpretation is left to statistical significance, which is not always well correlated with clinical significance. CONCLUSIONS: To propose the most adequate treatment in patient's interest, we need results focused on patients that combine not only quantity or overall survival but also quality of life. Parameters such as QALY should be included in clinical trials as evaluation objectives in order to favor decision taking

[What has changed in the epidemiology and screening of prostate cancer?]. / ¿Qué ha cambiado en la epidemiología y el cribado del cáncer de próstata?

OBJECTIVE; The objective of this study is to review the evolution and changes of prostate cancer epidemiology and to perform an analysis of the current status of prostate cancer screening based on the various studies and scientific societies recommendations. METHODS; We performed a bibliographic review of relevant papers in relation to prostate cancer epidemiology and screening, with special focus on international and multicentric trials on population screening. RESULTS; The current number and profile of patients being diagnosed of prostate cancer have changed significantly from the pre-PSA era to the present time. Early diagnosis and screening strategies have caused an increase in incidence and a decrease in cancer mortality in some countries. CONCLUSIONS; Systematic screening, despite inconsistencies in some studies, seems to improve prostate cancer specific mortality. The introduction of new biomarkers, imaging techniques such as mpMRI as well as less aggressive therapeutic alternatives, probably open windows to the future for a better diagnosis and treatment of the disease.

¿Qué ha cambiado en la epidemiología y el cribado del cáncer de próstata? / What has changed in the epidemiology and screening of prostate cancer?

OBJETIVO: El objetivo del presente estudio es examinar la evolución y los cambios en la epidemiología del cáncer de próstata y realizar un análisis del estado actual en el cribado del cáncer de próstata en base a los distintos estudios y de las recomendaciones de las sociedades científicas. MÉTODO: Se ha realizado una revisión bibliográfica de trabajos relevantes en relación con la epidemiología y el cribado del cáncer de próstata, con especial atención a los ensayos internacionales y multicéntricos sobre el screening poblacional. RESULTADOS: El número y perfil de los pacientes diagnosticados de cáncer de próstata en la actualidad ha cambiado de forma significativa desde los periodos pre-PSA a la actualidad. El diagnóstico precoz y las estrategias de cribado han hecho que haya aumentado su incidencia y que la mortalidad por cáncer haya disminuido en muchos países. CONCLUSIÓN: El despistaje sistemático parece, aunque existen inconsistencias en algunos estudios, poder mejorar la mortalidad específica por cáncer de próstata. La introducción de nuevos biomarcadores, técnicas de imagen como la mpRNM así como alternativas terapéuticas menos agresivas, posiblemente nos abren ventanas al futuro para un mejor diagnóstico y tratamiento de la enfermedad

OBJECTIVE: The objective of this study is to review the evolution and changes of prostate cancer epidemiology and to perform an analysis of the current status of prostate cancer screening based on the various studies and scientific societies recommendations. METHODS: We performed a bibliographic review of relevant papers in relation to prostate cancer epidemiology and screening, with special focus on international and multicentric trials on population screening. RESULTS: The current number and profile of patients being diagnosed of prostate cancer have changed significantly from the pre-PSA era to the present time. Early diagnosis and screening strategies have caused an increase in incidence and a decrease in cancer mortality in some countries. CONCLUSIONS: Systematic screening, despite inconsistencies in some studies, seems to improve prostate cancer specific mortality. The introduction of new biomarkers, imaging techniques such as mpMRI as well as less aggressive therapeutic alternatives, probably open windows to the future for a better diagnosis and treatment of the disease

[Criticisms to patient selection in active surveillance in prostate cancer]. / Criticas a la selección de pacientes en vigilancia activa en cancer de prostata.

OBJECTIVES: Active treatment in localized prostate cancer, in its various types, is assumed as a valid alternative. The effect of the possible overtreatment has raised that options such as active surveillance are offered as an alternative to active treatments, without evidence about its validity in many points. The objective of this study is to analyze the current controversies to define candidates to this alternative, follow up criteria, impact on quality of life and evidence bases to do it. METHODS: We perform an analysis updating the Medline search with the terms localized prostate cancer and active surveillance, analyzing the articles and their evidence, as well as guidelines recommendations. RESULTS: Selection criteria for candidates to active surveillance are heterogeneous, without evidence of uniformity. Likewise, follow up and its criteria or progression are not well defined. The impact on progression, or delay in decision-making, have not been analyzed and we lack of studies of highest evidence including comparative studies for cancer specific or global survival results. CONCLUSIONS: Although AS seems to be a reasonable alternative in many patients with localized prostate cancer, we still need to define many features of inclusion and decision-making. Comparative studies are needed to better define selection and validity of active surveillance.

Críticas a la selección de pacientes en vigilancia activa en cáncer de próstata / Criticisms to patient selection in active surveillance in prostate cancer

OBJETIVO: El tratamiento activo del cáncer de próstata localizado, en sus diferentes formas, es asumido como una alternativa válida. El efecto del posible sobretratamiento ha planteado que opciones como la vigilancia activa se oferte como alternativa a los tratamientos activos, sin en muchos puntos evidencias importantes sobre su validez. El objetivo de este estudio es analizar las controversias actuales para definir candidatos a esta alternativa, criterios de seguimiento, impacto en calidad de vida y bases de evidencia para ello. MÉTODO: Realizamos un análisis actualizando con la búsqueda en medlinede términos cáncer de próstata localizado y active surveillance-vigilancia activa "VA", analizando los diferentes trabajos y sus evidencias, así como recomendaciones en guías clínicas. RESULTADOS: Los criterios de selección de los pacientes candidatos a seguimiento activo son heterogéneos, sin una evidencia de uniformidad. El seguimiento y criterios del mismo o progresión igualmente están mal definidos. El impacto en la progresión o retraso en la toma de decisiones no está analizado y carecemos de estudios de máxima evidencia sobre estudios comparativos para resultados de supervivencia cáncer específica o global. CONCLUSIONES: Aunque la VA parece una alternativa razonable en muchos pacientes con CPL, la inclusión y toma de decisiones, todavía necesitan de muchas aspectos por definir, siendo necesarios estudios comparativos que puedan definir mejor la selección y validez de seguimiento activo

OBJECTIVES: Active treatment in localized prostate cancer, in its various types, is assumed as a valid alternative. The effect of the possible overtreatment has raised that options such as active surveillance are offered as an alternative to active treatments, without evidence about its validity in many points. The objective of this study is to analyze the current controversies to define candidates to this alternative, follow up criteria, impact on quality of life and evidence bases to do it. METHODS: We perform an analysis updating the Medline search with the terms localized prostate cancer and active surveillance, analyzing the articles and their evidence, as well as guidelines recommendations. RESULTS: Selection criteria for candidates to active surveillance are heterogeneous, without evidence of uniformity. Likewise, follow up and its criteria or progression are not well defined. The impact on progression, or delay in decision-making, have not been analyzed and we lack of studies of highest evidence including comparative studies for cancer specific or global survival results. CONCLUSIONS: Although AS seems to be a reasonable alternative in many patients with localized prostate cancer, we still need to define many features of inclusion and decision-making. Comparative studies are needed to better define selection and validity of active surveillance

[Testosterone deficit syndrome in the old male]. / Síndrome de deficit de testosterona en el anciano.

Epidemiological studies have demonstrated that prevalence of hypogonadism in old males increases with every additional decade of life. These males present various symptoms including decrease of sexual function, decrease of cognitive function, altered lipid profile, increased visceral adiposity, changes in bone density and muscular strength secondary to atrophy. Currently, testosterone injections and gel preparations are the most used. Testosterone replacement therapy provides significant symptomatic improvements for men with late start hypogonadism. Long-term benefits and risks of testosterone replacement therapy will be more evident when testosterone effects are studied on all health related parameters over a prolonged period of time. There is a large ongoing multicentric randomized clinical trial sponsored by NIH for testosterone control in old men with low testosterone levels. Its results may give answers to the possible benefits and risks of testosterone replacement in aging males. If an aging male is diagnosed as late-start hypogonadism, the urologist should discuss with the patient potential benefits and risks of testosterone therapy. Aging males with significant erythrocytosis, untreated sleep apnea, prostate cancer and high risk of cardiovascular events must be excluded from testosterone replacement therapy. Currently, there are not enough evidences to clearly state that the benefits of testosterone replacement therapy in aging males are better than the risks of this treatment. A general recommendation cannot be given that testosterone replacement therapy may be applied to all aging males with low testosterone levels independently of significant signs or symptoms.

Síndrome de déficit de testosterona en el anciano / Testosterone deficit syndrome in the old male

Los estudios epidemiológicos han demostrado que la prevalencia de hipogonadismo en los hombres de edad avanzada aumenta con cada década adicional de vida. Estos hombres presentan diversos síntomas que incluyen la disminución de la función sexual, disminución de la función cognitiva, perfil lipídico alterado, aumento de la adiposidad visceral, cambios en la densidad ósea y en la fuerza muscular secundaria a la atrofia. En la actualidad, las inyecciones de testosterona y preparaciones en forma de gel son las más usadas. La terapia de reemplazo de testosterona proporciona mejoras significativas en los síntomas para hombres con hipogonadismo de inicio tardío. Los beneficios a largo plazo y los riesgos del tratamiento con testosterona de reemplazo se harán más evidentes cuando los efectos de la testosterona se estudian en todos los parámetros relacionados con la salud durante un período prolongado de tiempo. Está en curso un gran ensayo multicéntrico aleatorizado patrocinado por NIH para el control de la testosterona en hombres de edad avanzada con niveles bajos de testosterona. Sus resultados pueden dar respuestas a los posibles beneficios y riesgos de reemplazo de testosterona en los hombres que envejecen. Si se produce un envejecimiento masculino se diagnostica como hipogonadismo de inicio tardío, el urólogo debe consensuar con el paciente los beneficios y riesgos potenciales de la terapia con testosterona (AU)

Los hombres ancianos que tienen eritrocitosis significativa, apnea del sueño no tratada, cáncer de próstata, y alto riesgo de eventos cardiovasculares deben ser excluidos de la terapia de reemplazo de testosterona. En la actualidad, no hay pruebas suficientes para afirmar claramente que los beneficios de la terapia de reemplazo de testosterona es mejor que los riesgos de este tratamiento de reemplazo en los hombres que envejecen. No se puede hacer una recomendación generalizada de que esta terapia de reemplazo de testosterona puede ser aplicada a todos los varones ancianos con niveles bajos de testosterona independientes de los signos o síntomas significativos (AU)

Epidemiological studies have demonstrated that prevalence of hypogonadism in old males increases with every additional decade of life. These males present various symptoms including decrease of sexual function, decrease of cognitive function, altered lipid profile, increased visceral adiposity, changes in bone density and muscular strength secondary to atrophy. Currently, testosterone injections and gel preparations are the most used. Testosterone replacement therapy provides significant symptomatic improvements for men with late start hypogonadism. Long-term benefits and risks of testosterone replacement therapy will be more evident when testosterone effects are studied on all health related parameters over a prolonged period of time. There is a large ongoing multicentric randomized clinical trial sponsored by NIH for testosterone control in old men with low testosterone levels. Its results may give answers to the possible benefits and risks of testosterone replacement in aging males. If an aging male is diagnosed as late-start hypogonadism, the urologist should discuss with the patient potential benefits and risks of testosterone therapy. Aging males with significant erythrocytosis, untreated sleep apnea, prostate cancer and high risk of cardiovascular events must be excluded from testosterone replacement therapy. Currently, there are not enough evidences to clearly state that the benefits of testosterone replacement therapy in aging males are better than the risks of this treatment. A general recommendation cannot be given that testosterone replacement therapy may be applied to al aging males with low testosterone levels independently of significant signs or symptoms (AU)

Mesothelioma of the tunica vaginalis. Case report.

OBJECTIVE: To report a case of a mesothelioma of the tunica vaginalis and to review the published literature. METHODS / RESULTS: A 61-year-old patient complained of one-month increase of right scrotum size with pain. An ultrasound showed a right hydrocele with a mass attached to the tunica vaginalis. He didn't refer any urological history or known exposure to asbestos. Blood levels of tumor markers (alpha-fetoprotein and beta-HCG) were within normal limits. We performed a radical inguinal orchiectomy with an en-bloc resection of the tunica vaginalis. The pathology described a potentially malignant biphasic mesothelioma. The patient has remained asymptomatic with negative extension studies after 10 years of follow up. CONCLUSIONS: Paratesticular mesotheliomas are rare tumors (approximately 250 cases reported )with uncertain etiology (only 30-40% are associated with asbestos exposure). The age range is between 50-70 years. Its presentation is usually as a scrotal mass with recurrent reactive hydrocele, which may delay early diagnosis. During surgery, intraoperative biopsy is recommended. It is important to do a differential diagnosis with other benign diseases. Treatment is only curative in early stages with radical orchidectomy and resection in-block of the tunica vaginalis. Despite being multidisciplinary, it is not curative in most cases due to rapid local and distant spread.

Mesotelioma de la túnica vaginal / Mesothelioma of the tunica vaginalis. Case report

OBJETIVO: Presentar un caso de mesotelioma testicular y realizar una revisión de la literatura publicada. MÉTODOS/RESULTADOS: Varón de 61 años que consulta por aumento del hemiescroto derecho desde hace 1 mes asociado a dolor. En una ecografía se visualizó hidrocele derecho con una masa en el interior. No refería ningún antecedente urológico de interés ni exposición conocida a asbestos. Los niveles sanguíneos de los marcadores tumorales alfa fetoproteína y beta-HCG estaban en dentro de la normalidad. Se realizó una orquiectomía radical vía inguinal con extirpación de la vaginal en bloque. La anatomía patológica describía un mesotelioma bifásico de la tunica vaginal potencialmente maligno. El paciente ha permanecido asintomático con periódicos estudios de extensión negativos tras 10 años de seguimiento. CONCLUSIONES: Los mesoteliomas testiculares son tumores muy poco frecuentes (aprox. 250 casos publicados) con una etiología incierta (sólo el 30-40% están asociados con exposición a asbesto) y una edad de presentación de entre los 50-70 años. Suelen manifestarse como una masa escrotal con hidrocele reactivo y recidivante, lo cual puede dificultar un diagnóstico precoz. Durante la cirugía se recomienda realizar biopsias intraoperatorias para obtener un diagnostico de certeza. Es importante realizar un diagnóstico diferencial con otras patologías benignas. El tratamiento sólo es curativo en estadios precoces mediante orquiectomía radical con extirpación en bloque de la vaginal. En la mayoría de los casos hay una rápida diseminación local y a distancia con mal pronostico a pesar de un tratamiento multidisciplinar (AU)

OBJECTIVE: To report a case of a mesothelioma of the tunica vaginalis and to review the published literature. METHODS / RESULTS: A 61-year-old patient complained of one-month increase of right scrotum size with pain. An ultrasound showed a right hydrocele with a mass attached to the tunica vaginalis. He didn’t refer any urological history or known exposure to asbestos. Blood levels of tumor markers (alpha-fetoprotein and beta-HCG) were within normal limits. We performed a radical inguinal orchiectomy with an en-bloc resection of the tunica vaginalis. The pathology described a potentially malignant biphasic mesothelioma. The patient has remained asymptomatic with negative extension studies after 10 years of follow up. CONCLUSIONS: Paratesticular mesotheliomas are rare tumors (approximately 250 cases reported) with uncertain etiology (only 30-40% are associated with asbestos exposure). The age range is between 50-70 years. Its presentation is usually as a scrotal mass with recurrent reactive hydrocele, which may delay early diagnosis. During surgery, intraoperative biopsy is recommended. It is important to do a differential diagnosis with other benign diseases. Treatment is only curative in early stages with radical orchidectomy and resection in-block of the tunica vaginalis. Despite being multidisciplinary, it is not curative in most cases due to rapid local and distant spread (AU)