Nuevas inmunoterapias en el cáncer de vejiga no músculo-invasivo de alto riesgo: estado actual y perspectivas de futuro / New immunotherapies for high-risk non-muscle invasive bladder cancer: Current state and future perspectives

CONTEXTO: El tratamiento estándar de los tumores de vejiga no músculo-invasivos (TVNMI) de alto riesgo es la resección transuretral de vejiga e instilaciones de bacilo de Calmette-Guérin (BCG). Sin embargo, las respuestas son limitadas. Es necesario buscar nuevas alternativas terapéuticas para estos pacientes. Los resultados en tumores avanzados de los inhibidores de puntos de control han dado lugar al interés en el uso de estas moléculas en TVNMI. MÉTODOS: Hemos realizado una búsqueda en PubMed utilizando los términos «bladder cancer» y «check point inhibitors». Para la búsqueda de ensayos clínicos, hemos utilizado los buscadores clinicaltrials.gov y clinicaltrialsregister.eu RESULTADOS: Actualmente hay 5 ensayos en marcha de pacientes no tratados con BCG. No hay resultados disponibles. En cuanto a los pacientes no respondedores a BCG, existen 15 ensayos en marcha, 2 de ellos con resultados preliminares: el Keynote 057, con resultados prometedores con pembrolizumab y que ha llevado a la FDA a aprobar su uso en enero de 2020 y el SWOG S1605, que ha mostrado resultados similares con atezolizumab. Otros ensayos administran estos fármacos intravesicalmente, una opción atractiva si resulta efectiva para el control oncológico. CONCLUSIONES: Los inhibidores de puntos de control ofrecen una nueva posibilidad para los pacientes no respondedores al BCG. Probablemente en el futuro se podrán usar en pacientes no tratados previamente con BCG. Los datos preliminares de ensayos clínicos muestran resultados prometedores. Es importante un buen conocimiento de estas moléculas por los urólogos y la formación de equipos multidisciplinares para ofrecer las mejores alternativas terapéuticas a estos pacientes

BACKGROUND: The standard treatment for high-risk non-muscle invasive bladder tumors (NMIBT) is transurethral resection of the bladder and BCG instillations. However, responses are limited, and new therapeutic alternatives for these patients are required. The results of checkpoint inhibitors in advanced tumors have led to interest in the use of these molecules in NMIBT. METHODS: We conducted a search on PubMed using the terms «bladder cancer» and «check point inhibitors». We have used the search engines clinicaltrials.gov and clinicaltrialsregister.eu for the search of clinical trials. RESULTS: There are currently 5 trials in progress on BCG untreated patients. There are no results available. As for BCG non-responders, there are 15 ongoing trials, two of them with preliminary results: Keynote 057, with promising results with pembrolizumab, which has led the FDA to approve its use in January 2020, and SWOG S1605, which has shown similar results with atezolizumab. Other trials are using intravesical administration of these drugs, which is an attractive option if it is effective for cancer control. CONCLUSIONS: Checkpoint inhibitors offer a new possibility for patients who do not respond to BCG. These will probably be used in the future for previously BCG untreated patients. Preliminary data from clinical trials show promising results. A good understanding of these molecules by urologists and the creation of multidisciplinary teams are crucial in order to offer the best therapeutic alternatives to these patients

New immunotherapies for high-risk non-muscle invasive bladder cancer: Current state and future perspectives. / Nuevas inmunoterapias en el cáncer de vejiga no músculo-invasivo de alto riesgo: estado actual y perspectivas de futuro.

BACKGROUND: The standard treatment for high-risk non-muscle invasive bladder tumors (NMIBT) is transurethral resection of the bladder and BCG instillations. However, responses are limited, and new therapeutic alternatives for these patients are required. The results of checkpoint inhibitors in advanced tumors have led to interest in the use of these molecules in NMIBT. METHODS: We conducted a search on PubMed using the terms «bladder cancer¼ and «check point inhibitors¼. We have used the search engines clinicaltrials.gov and clinicaltrialsregister.eu for the search of clinical trials. RESULTS: There are currently 5 trials in progress on BCG untreated patients. There are no results available. As for BCG non-responders, there are 15 ongoing trials, two of them with preliminary results: Keynote 057, with promising results with pembrolizumab, which has led the FDA to approve its use in January 2020, and SWOG S1605, which has shown similar results with atezolizumab. Other trials are using intravesical administration of these drugs, which is an attractive option if it is effective for cancer control. CONCLUSIONS: Checkpoint inhibitors offer a new possibility for patients who do not respond to BCG. These will probably be used in the future for previously BCG untreated patients. Preliminary data from clinical trials show promising results. A good understanding of these molecules by urologists and the creation of multidisciplinary teams are crucial in order to offer the best therapeutic alternatives to these patients.

Análisis coste-efectividad de las principales herramientas diagnósticas en mujeres con vejiga hiperactiva: historia clínica, diario miccional y estudio urodinámico / Cost-effectiveness analysis of main diagnosis tools in women with overactive bladder. Clinical history, micturition diary and urodynamic study

Objetivos: El presente trabajo de investigación clínica pretende analizar a la luz de la mejor evidencia científica el rendimiento y el coste de las principales herramientas utilizadas en el diagnóstico de la vejiga hiperactiva (VH). Métodos: Se trata de un estudio transversal exploratorio y analítico, en el cual se seleccionó una muestra de 199 mujeres diagnosticadas de VH entre los años 2006 y 2008, a las que se realizó de forma prospectiva: exploración física, análisis de orina, diario miccional (DM) y estudio urodinámico (EUD). Se asumió que un porcentaje de diagnóstico altamente sensible debería ser 80% y que una diferencia de diagnóstico del 10% entre las pruebas sería clínicamente relevante. Se determinó estadísticamente la sensibilidad de cada una de las pruebas de forma aislada y combinada para el diagnóstico de VH y una valoración de los recursos económicos directos e indirectos que conlleva su realización, analizándose el coste efectividad de la historia clínica (HC), DM y EUD para el diagnóstico de VH. Resultados: La sensibilidad global para el diagnóstico de VH es baja para cualquiera de las pruebas utilizadas de forma aislada, mientras que la combinación de 2 pruebas cualesquiera presenta una buena sensibilidad global para su diagnóstico. La combinación de HC y DM es la alternativa más coste efectiva en el diagnóstico de VH. Conclusiones: El uso de HC y DM es una combinación tan sensible para el diagnóstico de la VH como la asociación de cualquiera de ellas con el EUD, presentando además un menor coste económico

Objetives: The aim of the present clinical research is to analyze, in the light of the best scientific evidence, the performance and the cost of the main diagnostic tools for overactive bladder (OAB). Methods: It is an exploratory transversal study in which 199 women diagnosed of OAB between 2006 and 2008 were selected and underwent to following prospective analyses: physical examination, urine analysis, micturition diary (MD) and urodynamic study (UDS). A percentage of 80% was assumed as highly sensitive and a diagnostic difference among tests of 10% would be considered clinically relevant. Tests’ sensitivity for diagnosis of OAB was statistically established by two ways: isolated and combined. Besides, the direct and indirect costs of these tests performance were conducted. Cost-effectiveness study of clinical history (CH), MD and US for the diagnosis of OAB was performed. Results: Overall sensitivity for OAB diagnosis is low for the 3 tests used in isolated way, whilst the combination of any two tests shows good overall sensitivity. The combination of CH and MD has appeared as the most cost-effective alternative to OAB diagnosis. Conclusions: For OAB diagnosis, CH-DM combination shows the same sensitivity than the association of either of them with the UDS, but unlike to these, it shows the lowest cost

Development of urologic de novo malignancies after renal transplantation.

OBJECTIVES: The incidence of neoplasms in renal transplant recipients is higher than in general population. The increasing age of donors and recipients also increases the risk of developing malignancies, including genitourinary. The aim of this study is to analyze clinical aspects and management of this complication. MATERIALS AND METHODS: We conducted a retrospective analysis of 1365 patients who underwent renal transplantation between 1977 and 2010 who were 44.6 ± 14.9 years old at the time of transplantation. The median follow-up was 95.6 months (range, 18.0-236.0). Data were analyzed for sex, age, time from transplant to diagnosis, location, clinical stage, immunosuppression, treatment, follow-up, and evolution. RESULTS: We diagnosed 25 de novo urologic neoplasms (25/1365; 1.8%) in 24 patients, with a median follow-up of 32 months (range, 12.5-51.8) from the diagnosis. Sixteen were male (66.7%) and 8 female (33.3%), with a median age at diagnosis of 59 years (range, 56.0-65.5). The median time between the transplant and the diagnosis of the malignancy was 69 months (range, 40.0-116.5). There were 11 renal cell carcinomas (RCC; 11/25; 44%), 8 in native kidney and 3 in renal allograft; 9 prostate cancers (PCa; 9/25; 36%), 8 localized and 1 metastatic; and 5 transitional cell carcinomas (TCC; 5/25; 20%), 3 in bladder and 2 in renal allograft pelvis. Treatments performed were similar to those used in the nontransplanted population. RCC were treated with radical nephrectomy when affecting the native kidney, partial nephrectomy when affecting the allograft, or immunotherapy when metastatic. Patients with localized PCa were treated with radical prostatectomy, radiotherapy, or androgenic deprivation if there were comorbidities, and those metastatic with hormonal deprivation. Bladder TCCs were treated with transurethral resection or radical cystectomy. Pelvis TCCs affecting the allograft were treated with radical nephroureterectomy of the allograft including bladder cuff and pelvic lymphadenectomy. CONCLUSIONS: There exists an increased incidence of urologic tumors in kidney transplant recipients. Conventional treatments of these tumors are technically feasible. The risk of developing these tumors remains even in the long term. Because of their suitability for curative treatments, it is advisable to perform periodic screening for urologic cancers to achieve an early diagnosis.