[Current treatment options and future perspectives on first line metastatic bladder cancer.] / Presente y futuro del tratamiento del carcinoma vesical metastásico en primera línea.

OBJECTIVE: Over the last 30 years researchon metastatic bladder cancer has been slow and limited to chemotherapy. Chemotherapy has provided high initial response rates but very few complete responses that remain overtime. Recently, European medical agency has granted approval to immunotherapy inmetastatic disease. We will review the clinical trials that drove to EMA approval as well as new promising therapies for metastatic bladder cancer. METHODS: A search on PubMed and clinicaltrials.gov through the combination of the following words in English and Spanish was performed: "carcinoma urotelial","cáncer de vejiga", "localmente avanzado","metastásico", "inmunoterapia", "CTLA-4", "PD1","PDL-1", "atezolizumab", "nivolumab", "ipilimubab", "pembrolizumab", "avelumab", "durvalumab", "tremelimumab", "terapia antiangiogénica", "terapia molecular dirigida" e "inhibidores VEGF". RESULTS: Cisplatin chemotherapy-based regimens remain standard treatment for metastatic bladder cancer as per phase III trials. Immunotherapy is available for cisplatin-ineligible patients with high PD-L1 expression,including atezolizumab or pembrolizumab. Trials comparing immunotherapy, chemotherapy or antiangiogenic drugs o targeted drugs are recruiting. CONCLUSIONS: The publication of the comparative studies on chemotherapy and immunotherapy as well as targeted therapy would provide a window of opportunity for an effective personalized treatment. Those treatment would decrease side-effects as well.

OBJETIVO: Durante los últimos 30 años las investigaciones en carcinoma vesical metastásico han estado paralizadas, limitándose el tratamiento de dicha patología al empleo de fármacos quimioterápicos, los cuales, a pesar de presentar una elevada tasa de respuesta inicial, tienen excepcionales respuestas completas y mantenidas en el tiempo. Recientemente, la Agencia Europea del Medicamento ha autorizado el empleo de fármacos inmunoterápicos para el tratamiento de esta patología en estadío metastásico. Este artículo tiene como objeto el análisis de los ensayos clínicos que permitieron dicha autorización, así como la revisión de nuevas terapias para el tratamiento del carcinoma urotelial localmente avanzado o metastásico.MÉTODO: Búsqueda bibliográfica realizada en Pub-Med y ClinicalTrials.gov mediante la combinación de las palabras clave, en español e inglés: "carcinoma urotelial", "cáncer de vejiga", "localmente avanzado","metastásico", "inmunoterapia", "CTLA-4", "PD1", "PDL-1", "atezolizumab", "nivolumab", "ipilimubab", "pembrolizumab","avelumab", "durvalumab", "tremelimumab", "terapia antiangiogénica", "terapia molecular dirigida" e "inhibidores VEGF". RESULTADOS: La poliquimioterapia a base de cisplatino sigue siendo el estándar de tratamiento para el carcinoma vesical metastásico de acuerdo con los resultados de los ensayos clínicos fase III publicados, sólo considerándose la inmunoterapia con atezolizumab o permbrolizumab electiva en aquellos pacientes no aptos para recibir cisplatino con alta expresión PDL1. Actualmente, están en curso estudios comparativos de terapias quimioterápicas frente a inmunoterapia, así como múltiples combinaciones que buscan efecto aditivo con fármacos antiangiogénicos o terapias dirigidas. CONLUSIONES: La publicación de los ensayos comparativos que se encuentran actualmente en curso, junto con los previsibles progresos en terapia dirigida, implicarán la posibilidad de abrir una esperanzadora línea de trabajo dirigida hacia una terapia efectiva y personalizada, que permita reducir los eventos adversos atribuibles al empleo de fármacos quimioterápicos.

Presente y futuro del tratamiento del carcinoma vesical metastásico en primera línea / Current treatment options and future perspectives on first line metastatic bladder cancer

OBJETIVO: Durante los últimos 30 años las investigaciones en carcinoma vesical metastásico han estado paralizadas, limitándose el tratamiento de dicha patología al empleo de fármacos quimioterápicos, los cuales, a pesar de presentar una elevada tasa de respuesta inicial, tienen excepcionales respuestas completas y mantenidas en el tiempo. Recientemente, la Agencia Europea del Medicamento ha autorizado el empleo de fármacos inmunoterápicos para el tratamiento de esta patología en estadío metastásico. Este artículo tiene como objeto el análisis de los ensayos clínicos que permitieron dicha autorización, así como la revisión de nuevas terapias para el tratamiento del carcinoma urotelial localmente avanzado o metastásico. MÉTODO: Búsqueda bibliográfica realizada en PubMed y ClinicalTrials.gov mediante la combinación de las palabras clave, en español e inglés: "carcinoma urotelial", "cáncer de vejiga", "localmente avanzado", "metastásico", "inmunoterapia", "CTLA-4", "PD1", "PDL- 1", "atezolizumab", "nivolumab", "ipilimubab", "pembrolizumab", "avelumab", "durvalumab", "tremelimumab", "terapia antiangiogénica", "terapia molecular dirigida" e "inhibidores VEGF". RESULTADOS: La poliquimioterapia a base de cisplatino sigue siendo el estándar de tratamiento para el carcinoma vesical metastásico de acuerdo con los resultados de los ensayos clínicos fase III publicados, sólo considerándose la inmunoterapia con atezolizumab o permbrolizumab electiva en aquellos pacientes no aptos para recibir cisplatino con alta expresión PDL1. Actualmente, están en curso estudios comparativos de terapias quimioterápicas frente a inmunoterapia, así como múltiples combinaciones que buscan efecto aditivo con fármacos antiangiogénicos o terapias dirigidas. CONLUSIONES: La publicación de los ensayos comparativos que se encuentran actualmente en curso, junto con los previsibles progresos en terapia dirigida, implicarán la posibilidad de abrir una esperanzadora línea de trabajo dirigida hacia una terapia efectiva y personalizada, que permita reducir los eventos adversos atribuibles al empleo de fármacos quimioterápicos

OBJECTIVE: Over the last 30 years research on metastatic bladder cancer has been slow and limited to chemotherapy. Chemotherapy has provided high initial response rates but very few complete responses that remain overtime. Recently, European medical agency has granted approval to immunotherapy in metastatic disease. We will review the clinical trials that drove to EMA approval as well as new promising therapies for metastatic bladder cancer. METHODS: A search on PubMed and clinicaltrials. gov through the combination of the following words in English and Spanish was performed: "carcinoma urotelial", "cáncer de vejiga", "localmente avanzado", "metastásico", "inmunoterapia", "CTLA-4", "PD1", "PDL-1", "atezolizumab", "nivolumab", "ipilimubab", "pembrolizumab", "avelumab", "durvalumab", "tremelimumab", "terapia antiangiogénica", "terapia molecular dirigida" e "inhibidores VEGF". RESULTS: Cisplatin chemotherapy-based regimens remain standard treatment for metastatic bladder cancer as per phase III trials. Immunotherapy is available for cisplatin-ineligible patients with high PD-L1 expression, including atezolizumab or pembrolizumab. Trials comparing immunotherapy, chemotherapy or antiangiogenic drugs o targeted drugs are recruiting. CONCLUSIONS: The publication of the comparative studies on chemotherapy and immunotherapy as well as targeted therapy would provide a window of opportunity for an effective personalized treatment. Those treatment would decrease side-effects as well

[Abiraterone in castration resistant prostate cancer.] / Abiraterona en cáncer de próstata resistente a la castración.

OBJECTIVES: Prostate cancer is the most frequent neoplasia diagnosed in males. Treatment of metastatic prostate cancer is based on androgen deprivation therapy (ADT) up to its change to the castration resistance state. Recently, new molecules have been developed that significantly increase survival and quality of life of these patients. Abiraterone acetate in combination with prednisone is the first oral hormone therapy that contributed to this change in the approach of the disease. METHODS: Systematic bibliographic review about abiraterone in the treatment of metastatic castration resistant prostate cancer (CPRC), with data on efficacy, safety and quality of life. RESULTS: Treatment with abiraterone and prednisone has demonstrated a significant increase in overall survival (OS 34.7 vs 30.3 months) and radiologic progression free survival (RPFS 16.5 months vs 8.3 months) in comparison to placebo and prednisone in patients with metastatic castration resistant prostate cancer (mCPRC). It also demonstrated an increase in OS and RPFS compared to placebo plus prednisone in mCPRC patients after at least one cytotoxic chemotherapy based treatment (OS 15.8 vs 11.2 months; RPFS 5.6 vs 3.6 months). Side effects related to abiraterone therapy are mainly related with mineral corticoid excess (Hypertension, hypokalemia, fluid retention) and, to a lesser extent, transaminase alterations or cardiovascular effects. Perceived quality of life results show a benefit in the abiraterone treatment group. CONCLUSIONS: Abiraterone acetate is a new hormonal treatment for metastatic castration resistant prostate cancer both before and after chemotherapy. The results of the available studies demonstrate a significant improvement in terms of efficacy, with a tolerability profile generally acceptable, predictable and manageable, and an improvement in patient's perceived quality of life.

Abiraterona en cáncer de próstata resistente a la castración / Abiraterone in castration resistant prostate cancer

OBJETIVO: El cáncer de próstata es la neoplasia más frecuentemente diagnosticada en varones. El tratamiento del cáncer de próstata metastásico se basa en la terapia de deprivación androgénica (TDA) hasta su paso a un estado de resistencia a la castración. Recientemente, se han desarrollado moléculas que han aumentado significativamente la supervivencia y la calidad de vida de estos pacientes. Acetato de abiraterona en combinación con prednisona es la primera hormonoterapia oral que ha contribuido a este cambio en el abordaje sobre la enfermedad. Metodos: Revisión sistemática de la literatura existente sobre abiraterona en el tratamiento del cáncer de próstata metastásico resistente a la castración, con datos de eficacia, seguridad y calidad de vida. RESULTADOS: El tratamiento con abiraterona y prednisona ha demostrado aumentar de manera significativa la supervivencia global (SG 34,7 vs 30,3 meses) y libre de progresión radiológica (SLPr: 16,5 meses vs 8,3 meses) respecto a placebo y prednisona de los pacientes con cáncer de próstata resistente a la castración metastásico. Asimismo, demostró aumentar la SG y SLPr frente a placebo más prednisona en pacientes con CPRCm tras al menos un tratamiento basado en quimioterapia citotóxica (SG 15,8 versus 11,2 meses; SLPr 5,6 versus 3,6 meses). Los efectos secundarios del tratamiento con abiraterona se relacionan fundamentalmente con el exceso de mineralcorticoides (hipertensión, hipopotasemia, retención de líquidos) y, en menor medida, alteraciones de las transaminasas o efectos cardiovasculares. Los resultados de calidad de vida percibidos por los pacientes muestran un beneficio en el grupo de tratamiento con abiraterona. CONCLUSIONES: Acetato de abiraterona es un nuevo tratamiento hormonal para el cáncer de próstata metastásico resistente a la castración tanto previamente como después de quimioterapia. Los resultados de los estudios existentes demuestran una mejoría significativa en términos de eficacia, con un perfil de tolerabilidad por lo general aceptable, predecible y manejable, y una mejora en la calidad de vida percibida por el paciente

OBJECTIVES: Prostate cancer is the most frequent neoplasia diagnosed in males. Treatment of metastatic prostate cancer is based on androgen deprivation therapy (ADT) up to its change to the castration resistance state. Recently, new molecules have been developed that significantly increase survival and quality of life of these patients. Abiraterone acetate in combination with prednisone is the first oral hormone therapy that contributed to this change in the approach of the disease. METHODS: Systematic bibliographic review about abiraterone in the treatment of metastatic castration resistant prostate cancer (CPRC), with data on efficacy, safety and quality of life. RESULTS: Treatment with abiraterone and prednisone has demonstrated a significant increase in overall survival (OS 34.7 vs 30.3 months) and radiologic progression free survival (RPFS 16.5 months vs 8.3 months) in comparison to placebo and prednisone in patients with metastatic castration resistant prostate cancer (mCPRC). It also demonstrated an increase in OS and RPFS compared to placebo plus prednisone in mCPRC patients after at least one cytotoxic chemotherapy based treatment (OS 15.8 vs 11.2 months; RPFS 5.6 vs 3.6 months). Side effects related to abiraterone therapy are mainly related with mineral corticoid excess (Hypertension, hypokalemia, fluid retention) and, to a lesser extent, transaminase alterations or cardiovascular effects. Perceived quality of life results show a benefit in the abiraterone treatment group. CONCLUSIONS: Abiraterone acetate is a new hormonal treatment for metastatic castration resistant prostate cancer both before and after chemotherapy. The results of the available studies demonstrate a significant improvement in terms of efficacy, with a tolerability profile generally acceptable, predictable and manageable, and an improvement in patient's perceived quality of life

Laparoscopic Nephrectomy for the Management of Xanthogranulomatous Pyelonephritis: Still a Challenging Procedure.

OBJECTIVE: The aim of the study was to assess the feasibility of laparoscopic nephrectomy (LN) in the treatment of patients with xanthogranulomatous pyelonephritis (XGP). METHODS: Retrospective review of medical records of 17 patients (mean age 60.0 ± 13.3 years) who underwent LN by a single surgeon from 2010 to 2018. Sociodemographic and clinical data including diagnosis, presenting clinical features, surgical management, and postoperative course were analyzed. RESULTS: LN was successfully performed in 15 (88.2%) patients. Two (12.5%) patients with disseminated disease were electively converted to open nephrectomy (ON) due to failure to progress. Two (11.8%) patients experienced intraoperative complications (grades 3b and 4b). Among patients in whom LN was successfully performed (n = 15), the mean operative time was 198.0 ± 107.1 min and was shorter when no intraoperative complications occurred (169.0 ± 48.1 min). Three (20%) of these patients required transfusions and nine (60.0%) required postoperative pelvic drainage (PD). Six (40%) patients experienced postoperative complications: one grade 1, four grade 2, and one grade 5. Mean hospital stay was 4.4 ± 4.3 days, and 3.4 ± 2.2 for those experiencing manageable or no complications. Among patients without postoperative complications (n = 6), mean hospital stay was shorter when no PD was placed (1.6 vs 2.6 days). CONCLUSION: LN is a feasible surgical option in patients with XGP although given the nature of XGP, it is associated with complications-nearly all manageable-which makes it a challenging surgical procedure. Advanced laparoscopic skills and experiences are needed. Dissemination of the disease is associated with the occurrence of more severe complications and conversion to ON. PD placement seems associated with shorter hospital stay.

[Laparoscopic uretero-ureterostomy for iatrogenic lesions of the distal uréter.] / Uretero­ureterostomía laparoscópica en las lesiones iatrogénicas del uréter distal.

OBJECTIVES: The most frequent ureteral lesions are iatrogenic, mainly due to gynecologic and urologic procedures. The resolution and repair of these lesions, when they require surgery, is often the performance of ureteroneocystostomy. We describe the technique for the repair of distal ureter lesions that preserves both anatomy and function of the urinary tract (1). The operation consists in dissection and extraction of the distal ureteral stump from its intramural tract to get at least 1 cm of free ureter, percutaneous insertion of a ureteral stent, checking the absence of tension between proximal ureter and distal dissected stump, end to end anastomosis and reinsertion of the distal ureter in the previously dissected bladder muscle layer. We present 4 cases of ureteral injury after laparoscopic simple total hysterectomy for uterine myomas with complete section of the distal ureter, that were operated 3-5 days after injury, performing laparoscopic repair surgery. We performed clinical and radiological control with intravenous urography demonstrating ureteral continuity normalization and good renal function. We believe that repair of the urinary tract with anatomical and physiological preservation must be the first option in the laparoscopic treatment of complete distal ureteral injuries, and intramural ureter dissection when needed avoids the performance of ureteroneocystostomy. It is necessary to keep progressing in the technique improvement, and to increase the number of cases and experience.

Uretero-ureterostomía laparoscópica en las lesiones iatrogénicas del uréter distal / Laparoscopic uretero-ureterostomy for iatrogenic lesions of the distal uréter

OBJETIVO: Las lesiones ureterales más frecuentes son las iatrógenas, fundamentalmente debidas a procedimientos ginecológicos y urológicos. Habitualmente la resolución y reparación de estas lesiones, cuando precisan cirugía, es la realización de una ureteroneocistostomía. Describimos una técnica para la reparación de lesiones de ureter distal que preserva tanto la anatomía como la función de la vía urinaria (1). La cirugía consiste en la disección y extracción del muñón ureteral distal de su trayecto intramural, para conseguir al menos 1 centímetro de uréter libre, colocación de stent ureteral por vía percutánea, comprobación de ausencia de tensión entre uréter proximal y muñón distal disecado, anastomosis término-terminal y reinserción de uréter distal en capa muscular vesical previamente disecada para la anastomosis. Presentamos 4 casos de lesión ureteral tras histerectomía total simple laparoscópica por miomas con sección completa de uréter distal, que se intervienen entre 3 y 5 días tras la lesión, realizando cirugía de reparación por vía laparoscópica. Se realiza control clínico y radiológico con urografía observando normalización de la continuidad ureteral y buen funcionalismo renal. Pensamos que la reparación con preservación anatómica y fisiológica de la vía urinaria, debe ser la primera opción en el tratamiento laparoscópico de las lesiones completas de uréter distal, y que la disección del uréter intramural en casos necesarios evita la realización de una ureteroneocistostomía. Es preciso seguir avanzando en el perfeccionamiento de la técnica y aumentar el número de casos y la experiencia

OBJECTIVES: The most frequent ureteral lesions are iatrogenic, mainly due to gynecologic and urologic procedures. The resolution and repair of these lesions, when they require surgery, is often the performance of ureteroneocystostomy. We describe the technique for the repair of distal ureter lesions that preserves both anatomy and function of the urinary tract (1). The operation consists in dissection and extraction of the distal ureteral stump from its intramural tract to get at least 1 cm of free ureter, percutaneous insertion of a ureteral stent, checking the absence of tension between proximal ureter and distal dissected stump, end to end anastomosis and reinsertion of the distal ureter in the previously dissected bladder muscle layer. We present 4 cases of ureteral injury after laparoscopic simple total hysterectomy for uterine myomas with complete section of the distal ureter, that were operated 3-5 days after injury, performing laparoscopic repair surgery. We performed clinical and radiological control with intravenous urography demonstrating ureteral continuity normalization and good renal function. We believe that repair of the urinary tract with anatomical and physiological preservation must be the first option in the laparoscopic treatment of complete distal ureteral injuries, and intramural ureter dissection when needed avoids the performance of ureteroneocystostomy. It is necessary to keep progressing in the technique improvement, and to increase the number of cases and experience