Multidisciplinary consensus document on the current treatment of bacille Calmette-Guérin-unresponsive non-muscle invasive bladder tumor.

Radical cystectomy is the current treatment of choice for patients with BCG-unresponsive non-muscle invasive bladder tumor (NMIBC). However, the high comorbidity of this surgery and its effects on the quality of life of patients require the investigation and implementation of bladder-sparing treatment options. These must be evaluated individually by the uro-oncology committee based on the characteristics of the BCG failure, type of tumor, patient preferences and treatment options available in each center. Based on FDA-required oncologic outcomes (6-month complete response rate for CIS: 50%; duration of response in responders for CIS and papillary: 30% at 12 months and 25% at 18 months), there is not currently a strong preference for one treatment over another, although the intravesical route seems to offer less toxicity. This work summarizes the evidence on the management of BCG-unresponsive NMIBC based on current scientific evidence and provides consensus recommendations on the most appropriate treatment.

Impacto de los sistemas de nefrometría renal en la valoración de las complicaciones en el tratamiento percutáneo guiado por imagen de las masas renales de pequeño tamaño / Usefulness of renal nephrometry scoring systems in the prediction of complications associated to percutaneous image-guided treatment for small renal masses

Introducción Los tumores renales son un desafío para los profesionales de la salud debido a su creciente prevalencia y complejidad de manejo. El estudio investiga la utilidad de los sistemas de nefrometría renal R.E.N.A.L. score y Padua en la predicción de complicaciones de la crioablación percutánea (CA). Material y métodos El estudio analiza de forma prospectiva a 90 pacientes con carcinoma de células renales (CCR) estadio T1a tratados con crioablación, totalizando 101 tumores. Resultados Se estudiaron 90 pacientes con 101 tumores renales de pequeño tamaño que recibieron terapia crioablativa. Los pacientes tenían una edad media de 68 años y mayoría eran hombres (74,4%). La mayoría de los tumores eran menores a 4 cm (89,1%) y la puntuación media del Padua y R.E.N.A.L. scores fue de 8,65 y 7,35, respectivamente. Se observaron complicaciones en 12 casos. El PADUA y R.E.N.A.L. scores demostraron un poder predictivo moderado (área bajo la curva [AUC] = 0,58 y AUC = 0,63, respectivamente) para las complicaciones poscrioablación. Conclusiones La CA es un tratamiento seguro y efectivo para los tumores renales de pequeño tamaño. Los sistemas de nefrometría renal R.E.N.A.L. y Padua scores tienen un poder predictivo moderado para las complicaciones asociadas a la CA de tumores renales. (AU)

Introduction Due to their increasing prevalence and complex management, renal tumors are challenging for health professionals. The study aims to evaluate the usefulness of R.E.N.A.L. and PADUA nephrometry scores in the prediction of complications after percutaneous cryoablation. Material and methods The study prospectively analyzed 90 patients with 101 stage T1a renal cell carcinoma (RCC) tumors treated with cryoablation. Results Ninety patients with 101 small renal tumors who received cryoablative therapy were investigated. The mean age of the patients was 68 years and 74.4% were male. Most tumors were smaller than 4 cm (89.1%) and the mean PADUA and R.E.N.A.L. scores were 8.65 and 7.35, respectively. Complications were observed in 12 cases. PADUA and R.E.N.A.L. scores demonstrated moderate predictive power (AUC = 0.58 and AUC = 0.63, respectively) for post-cryoablation complications. Conclusions Percutaneous cryoablation is a safe and effective treatment for small renal tumors. The R.E.N.A.L. and PADUA renal nephrometry scores have moderate predictive power for complications associated with percutaneous cryoablation of renal tumors. (AU)

Usefulness of renal nephrometry scoring systems in the prediction of complications associated to percutaneous image-guided treatment for small renal masses.

INTRODUCTION: Due to their increasing prevalence and complex management, renal tumors are challenging for health professionals. The study aims to evaluate the usefulness of R.E.N.A.L. and PADUA nephrometry scores in the prediction of complications after percutaneous cryoablation. MATERIAL AND METHODS: The study prospectively analyzed 90 patients with 101 stage T1a renal cell carcinoma (RCC) tumors treated with cryoablation. RESULTS: Ninety patients with 101 small renal tumors who received cryoablative therapy were investigated. The mean age of the patients was 68 years and 74.4% were male. Most tumors were smaller than 4 cm (89.1%) and the mean PADUA and R.E.N.A.L. scores were 8.65 and 7.35, respectively. Complications were observed in 12 cases. PADUA and R.E.N.A.L. scores demonstrated moderate predictive power (AUC = 0.58 and AUC = 0.63, respectively) for post-cryoablation complications. CONCLUSIONS: Percutaneous cryoablation is a safe and effective treatment for small renal tumors. The R.E.N.A.L. and PADUA renal nephrometry scores have moderate predictive power for complications associated with percutaneous cryoablation of renal tumors.

Manejo del carcinoma in situ de tramo urinario superior diagnosticado por biopsia ureteroscópica: ¿es el bacilo de Calmette-Guérin una alternativa a la nefroureterectomía? / Management of primary upper urinary tract carcinoma in situ diagnosed by ureteroscopic biopsy: Is bacillus Calmette-Guerin an alternative to nephroureterectomy?

Introducción La nefroureterectomía radical (NFU) es el tratamiento estándar del carcinoma de tramo urinario superior (TUS). No obstante, desde 1985 se ha introducido el tratamiento conservador en el manejo del carcinoma in situ en TUS (cis-TUS). El objetivo de este estudio fue comparar la evolución oncológica de los pacientes con cis-TUS tratados en nuestro centro con NFU vs. instilaciones de bacilo de Calmette-Guérin (BCG). Métodos Se trata de un estudio retrospectivo de pacientes con diagnóstico de cis-TUS primario entre 1990-2018. Todos los pacientes presentaban diagnóstico histológico de cis-TUS con ausencia de otro carcinoma de TUS concomitante. La confirmación histológica se obtuvo mediante ureteroscopia con múltiples biopsias. Los pacientes fueron tratados mediante NFU, ureterectomía distal o instilaciones de BCG. Los datos clinicopatológicos y la evolución oncológica fue comparada entre los grupos NFU y BCG. Resultados Se incluyeron un total de 28 pacientes, 29 unidades renales (UR). Dieciséis (57,1%) pacientes (17 UR) recibieron BCG. Las instilaciones fueron administradas por nefrostomía en 4 pacientes, catéter en J simple en 5 y doble J en 7. La respuesta completa y la persistencia o recurrencia fueron detectadas en 10 (58,8%) y 7 (41,2) UR tratadas con BCG. Ocho UR (27,6%) fueron tratadas con NFU, con una recurrencia contralateral detectada en 4 casos (50%). Finalmente, 4 UR con cis-TUS (13,8%) fueron tratadas con ureterectomía distal. No se detectaron diferencias en la supervivencia libre de recurrencia (p=0,841) ni en la supervivencia cáncer específica (p=0,77) entre los grupos de NFU y BCG. Conclusiones Aunque la nefroureterectomía radical representa el tratamiento estándar para el CIS de tramo urinario superior, nuestros resultados confirman que las instilaciones con BCG también son efectivas. La confirmación histológica de cis-TUS debería realizarse previamente a la decisión terapéutica (AU)

Introduction Radical nephroureterectomy (RNU) still represents the gold standard treatment for upper tract urothelial carcinoma (UTUC); however, since the 1980s attempts have been made to treat upper urinary tract CIS (UT-CIS) conservatively. The aim of this study was to compare the outcome of patients with primary UT-CIS treated in our center by means of RNU vs. bacillus Calmette-Guérin (BCG) instillations. Methods This retrospective study included patients with diagnosis of primary UT-CIS between 1990 and 2018. All patients had histological confirmation of UT-CIS in the absence of other concomitant UTUC. Histological confirmation was obtained by ureteroscopy with multiple biopsies. Patients were treated with RNU, distal ureterectomy, or BCG instillations. Clinicopathological features and outcomes were compared between the RNU and BCG groups. Results A total of 28 patients and 29 renal units (RUs) were included. Sixteen (57.1%) patients (17 RUs) received BCG. BCG was administered via a nephrostomy tube in 4 patients, a single-J ureteral stent in 5, and a Double-J stent in 7. Complete response and persistence or recurrence were detected in ten (58.8%) and seven (41.2%) RUs treated with BCG, respectively. Eight (27.6%) RUs underwent RNU, with contralateral recurrence detected in four (50%), and 4 (13.8%) RUs underwent distal ureterectomy. No differences were found in recurrence-free survival (p=0.841) and cancer-specific survival (p=0.77) between the RNU and BCG groups. Conclusions Although RNU remains the gold standard treatment for UT-CIS, our results confirm that BCG instillations are also effective. Histological confirmation of UT-CIS is mandatory before any treatment (AU)

Reduced- vs full-dose BCG in bladder cancer: A systematic review and meta-analysis.

OBJECTIVE: To assess the oncologic outcomes and the safety profile of a reduced-dose versus full-dose BCG regimen in patients with non-muscle-invasive bladder cancer (NMIBC). MATERIAL AND METHODS: We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The PubMed, Embase, and Web of Science databases were searched in January 2022 for studies that analyzed oncological outcomes and compared between reduced- and full-dose BCG regimens. RESULTS: Seventeen studies including 3757 patients met our inclusion criteria. Patients who received reduced-dose BCG had significantly higher recurrence rates (OR 1.19; 95%CI, 1.03-1.36; p = 0.02). The risks of progression to muscle-invasive BC (OR 1.04; 95%CI, 0.83-1.32; p = 0.71), metastasis (OR 0.82; 95%CI, 0.55-1.22; p = 0.32), death from BC (OR 0.80; 95%CI, 0.57-1.14; p = 0.22), and all-cause death (OR 0.82; 95%CI, 0.53-1.27; p = 0.37) were not statistically different. When restricting the analyses to randomized controlled trials, we found similar results. In subgroup analysis, reduced dose was associated with a higher rate of BC recurrence in studies that used only an induction regimen (OR 1.70; 95%CI, 1.19-2.42; p = 0.004), but not when a maintenance regimen was used (OR 1.07; 95%CI, 0.96-1.29; p = 0.17). Regarding side effects, the reduced-dose BCG regimen was associated with fewer episodes of fever (p = 0.003), and therapy discontinuation (p = 0.03). CONCLUSION: This review found no association between BCG dose and BC progression, metastasis, and mortality. There was an association between reduced dose and BC recurrence, which was no longer significant when a maintenance regimen was used. In times of BCG shortage, reduced-dose regimens could be offered to BC patients.

Dosis reducida vs. dosis completa de BCG en el cáncer de vejiga: revisión sistemática y metaanálisis / Reduced- vs full-dose BCG in bladder cancer: a systematic review and meta-analysis

Objetivo Evaluar los resultados oncológicos y el perfil de seguridad de un régimen de Bacilo Calmette-Guérin (BCG) de dosis reducida frente a uno de dosis completa en pacientes con cáncer de vejiga no músculo infiltrante (CVNMI). Material y métodos Se realizó una revisión sistemática de acuerdo con la declaración Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Se realizaron búsquedas de estudios que analizaran los resultados oncológicos entre los regímenes de BCG con reducción de dosis y dosis completa en las bases de datos PubMed, Embase y Web of Science en enero del 2022. Resultados Diecisiete estudios que incluían a 3.757 pacientes cumplieron los criterios de inclusión. Los pacientes que recibieron reducción de dosis de BCG tuvieron tasas de recidiva significativamente mayores (OR 1,19; IC del 95%, 1,03-1,36; p = 0,02). Los riesgos de progresión a un cáncer de vejiga (CV) músculo infiltrante (OR 1,04; IC 95%, 0,83-1,32; p = 0,71), de metástasis (OR 0,82; IC 95%, 0,55-1,22; p = 0,32), de muerte por CV (OR 0,80; IC 95%, 0,57-1,14; p = 0,22) y de muerte por cualquier causa (OR 0,82; IC 95%, 0,53-1,27; p = 0,37) no fueron estadísticamente diferentes. Al restringir los análisis a ensayos controlados aleatorizados, se encontraron resultados similares. En el análisis de subgrupos, la reducción de dosis se asoció con una mayor tasa de recidiva de CV en los estudios que utilizaron solo un régimen de inducción (OR 1,70; IC 95%, 1,19-2,42; p = 0,004), lo cual no se observó cuando se empleó un régimen de mantenimiento (OR 1,07; IC 95%, 0,96-1,29; p = 0,17). En cuanto a los efectos secundarios, el esquema reducido de BCG se asoció con menos episodios de fiebre (p = 0,003) y de interrupción del tratamiento (p = 0,03). Conclusión Esta revisión no encontró ninguna asociación entre la dosis de BCG y la progresión, la metástasis y la mortalidad del CV (AU)

Objective To assess the oncologic outcomes and the safety profile of a reduced-dose versus full-dose BCG regimen in patients with non-muscle-invasive bladder cancer (NMIBC). Material and Methods We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The PubMed, Embase, and Web of Science databases were searched in January 2022 for studies that analyzed oncological outcomes and compared between reduced- and full-dose BCG regimens. Results seventeen studies including 3757 patients met our inclusion criteria. Patients who received reduced-dose BCG had significantly higher recurrence rates (OR 1.19; 95%CI, 1.03-1.36; p = 0.02). The risks of progression to muscle-invasive BC (OR 1.04; 95%CI, 0.83-1.32; p = 0.71), metastasis (OR 0.82; 95%CI, 0.55-1.22; p = 0.32), death from BC (OR 0.80; 95%CI, 0.57-1.14; p = 0.22), and all-cause death (OR 0.82; 95%CI, 0.53-1.27; p = 0.37) were not statistically different. When restricting the analyses to randomized controlled trials, we found similar results. In subgroup analysis, reduced dose was associated with a higher rate of BC recurrence in studies that used only an induction regimen (OR 1.70; 95%CI, 1.19-2.42; p = 0.004), but not when a maintenance regimen was used (OR 1.07; 95%CI, 0.96-1.29; p = 0.17). Regarding side effects, the reduced-dose BCG regimen was associated with fewer episodes of fever (p = 0.003), and therapy discontinuation (p = 0.03). Conclusion This review found no association between BCG dose and BC progression, metastasis, and mortality. There was an association between reduced dose and BC recurrence, which was no longer significant when a maintenance regimen was used. In times of BCG shortage, reduced-dose regimens could be offered to BC patients (AU)

Management of primary upper urinary tract carcinoma in situ diagnosed by ureteroscopic biopsy: Is bacillus Calmette-Guerin an alternative to nephroureterectomy?

BACKGROUND: Radical nephroureterectomy (RNU) represents the gold standard treatment for upper tract urothelial carcinoma (UTUC); however, attempts have been made to treat upper urinary tract CIS (UT-CIS) conservatively. The aim of this study was to compare the outcome of patients with primary UT-CIS treated in our center by means of RNU vs. bacillus Calmette-Guérin (BCG) instillations. METHODS: This retrospective study included patients with diagnosis of primary UT-CIS between 1990 and 2018. All patients had histological confirmation of UT-CIS in the absence of other concomitant UTUC. Histological confirmation was obtained by ureteroscopy with multiple biopsies. Patients were treated with BCG instillations, RNU or distal ureterectomy. Clinicopathological features and outcomes were compared between RNU and BCG groups. RESULTS: A total of 28 patients and 29 renal units (RUs) were included. Sixteen (57.1%) patients (17 RUs) received BCG. BCG was administered via nephrostomy tube in 4 patients, with a single-J ureteral stent in 5, and using a Double-J stent in 7. Complete response and persistence or recurrence were detected in ten (58.8%) and seven (41.2%) RUs treated with BCG, respectively. Eight (27.6%) RUs underwent RNU, and 4 (13.8%) Rus distal ureterectomy. No differences were found in recurrence-free survival (p=0.841) and cancer-specific survival (p=0.77) between the RNU and BCG groups. CONCLUSIONS: Although RNU remains the gold standard treatment for UT-CIS, our results confirm that BCG instillations are also effective. Histological confirmation of UT-CIS is mandatory before any treatment.

Antecedentes de neoplasias urológicas previos al trasplante renal. Resultados oncológicos a largo plazo / History of urological malignancies before kidney transplantation, oncological outcome on the long term

Introducción: Nuestro objetivo ha sido informar de los resultados oncológicos de pacientes con ERET y antecedentes de neoplasias urológicas que fueron sometidos posteriormente a un trasplante renal (TR).Material y métodoEstudio retrospectivo llevado a cabo en el registro de la Fundación Puigvert (Barcelona) con 1.200 TR realizados entre 1988 y 2018. Se identificaron 85 neoplasias urológicas que recibieron tratamiento previo al TR en 81 pacientes: 15 (18%) cánceres de próstata, 49 (58%) carcinoma de células renales (CCR), 19 (22%) carcinomas uroteliales y 2 (2%) cánceres de testículo. Se registraron datos de las características basales, la estadificación del cáncer, el tratamiento y el seguimiento, y sobre la cronología del inicio de diálisis, la inscripción en la lista de espera y el TR. Los criterios de valoración fueron la recidiva del cáncer, la progresión metastásica, la muerte específica por cáncer y la supervivencia global.ResultadosEn una mediana de seguimiento de 13,1 años (2,2-32), se registraron 16/85 (19%) recidivas del cáncer, con 3 (4%) progresiones a metástasis y muerte por cáncer. La mediana de supervivencia global tras el tratamiento del cáncer fue de 25,3 años y la supervivencia por cáncer específica fue del 95% a los 25 años.La mediana de tiempo desde el tratamiento del cáncer hasta el trasplante de riñón fue de 4,8 años: 3,7 años en el cáncer de próstata, 3,9 años en el CCR y 8,8 años en el cáncer vesical. La mediana de tiempo desde el inicio de diálisis hasta el TR fue de 1,8 años en los pacientes con antecedentes de neoplasia urológica, frente a 0,5 años en la cohorte total de 1.200 trasplantes renales durante el mismo periodo. (AU)

Introduction: We aimed to report the oncological outcomes of ESRD patients with histories of urological malignancies who were subsequently submitted to kidney transplantation (KT).Material and methodRetrospective study lead in the Puigvert Foundation (Barcelona) registry of 1,200 KT performed from 1988 to 2018. Eighty-five urological malignancies that were treated before KT in 81 patients were identified: 15 (18%) prostate cancers, 49 (58%) RCC, 19 (22%) urothelial carcinomas and 2 (2%) testicular cancers. Baseline characteristics, cancer staging, treatment and follow-up were registered as well as the chronology of the start of dialysis, inscription on the waiting list and kidney transplantation. Endpoints included were cancer recurrence, metastatic progression, cancer-specific death and overall survival.ResultsIn a median follow-up of 13.1 years (2.2-32), 16/85 (19%) cancer recurrences were reported, with 3 (4%) who progressed to metastasis and died of cancer. Median overall survival after cancer treatment was 25.3 years and cancer-specific survival was 95% at 25 years.Median time from cancer treatment to kidney transplantation was 4.8 years: 3.7 years in prostate cancer, 3.9 years in RCC and 8.8 years in bladder cancer. The median time from start of dialysis to kidney transplantation was 1.8 years in patients with histories of urological malignancy versus 0.5 year in the total cohort of 1,200 renal transplanted over the same period. (AU)

History of urological malignancies before kidney transplantation, oncological outcome on the long term.

INTRODUCTION: We aimed to report the oncological outcomes of ESRD patients with histories of urological malignancies who were subsequently submitted to kidney transplantation (KT). MATERIAL AND METHOD: Retrospective study lead in the Puigvert Foundation (Barcelona) registry of 1,200 KT performed from 1988 to 2018. Eighty-five urological malignancies that were treated before KT in 81 patients were identified: 15 (18%) prostate cancers, 49 (58%) RCC, 19 (22%) urothelial carcinomas and 2 (2%) testicular cancers. Baseline characteristics, cancer staging, treatment and follow-up were registered as well as the chronology of the start of dialysis, inscription on the waiting list and kidney transplantation. Endpoints included were cancer recurrence, metastatic progression, cancer-specific death and overall survival. RESULTS: In a median follow-up of 13.1 years (2.2-32), 16/85 (19%) cancer recurrences were reported, with 3 (4%) who progressed to metastasis and died of cancer. Median overall survival after cancer treatment was 25.3 years and cancer-specific survival was 95% at 25 years. Median time from cancer treatment to kidney transplantation was 4.8 years: 3.7 years in prostate cancer, 3.9 years in RCC and 8.8 years in bladder cancer. The median time from start of dialysis to kidney transplantation was 1.8 years in patients with histories of urological malignancy versus 0.5 year in the total cohort of 1,200 renal transplanted over the same period. CONCLUSIONS: Well-selected patients with histories of urological malignancies greatly benefit from kidney transplantation with infrequent and late cancer recurrence. Waiting time could be optimized in low-risk prostate cancer and RCC, but more robust data are needed.

History of urological malignancies before kidney transplantation, oncological outcome on the long term. / Antecedentes de neoplasias urológicas previos al trasplante renal. Resultados oncológicos a largo plazo.

INTRODUCTION: We aimed to report the oncological outcomes of ESRD patients with histories of urological malignancies who were subsequently submitted to kidney transplantation (KT). MATERIAL AND METHOD: Retrospective study lead in the Puigvert Foundation (Barcelona) registry of 1,200 KT performed from 1988 to 2018. Eighty-five urological malignancies that were treated before KT in 81 patients were identified: 15 (18%) prostate cancers, 49 (58%) RCC, 19 (22%) urothelial carcinomas and 2 (2%) testicular cancers. Baseline characteristics, cancer staging, treatment and follow-up were registered as well as the chronology of the start of dialysis, inscription on the waiting list and kidney transplantation. Endpoints included were cancer recurrence, metastatic progression, cancer-specific death and overall survival. RESULTS: In a median follow-up of 13.1 years (2.2-32), 16/85 (19%) cancer recurrences were reported, with 3 (4%) who progressed to metastasis and died of cancer. Median overall survival after cancer treatment was 25.3 years and cancer-specific survival was 95% at 25 years. Median time from cancer treatment to kidney transplantation was 4.8 years: 3.7 years in prostate cancer, 3.9 years in RCC and 8.8 years in bladder cancer. The median time from start of dialysis to kidney transplantation was 1.8 years in patients with histories of urological malignancy versus 0.5 year in the total cohort of 1,200 renal transplanted over the same period. CONCLUSIONS: Well-selected patients with histories of urological malignancies greatly benefit from kidney transplantation with infrequent and late cancer recurrence. Waiting time could be optimized in low-risk prostate cancer and RCC, but more robust data are needed.

Tratamientos actuales tras fracaso a BCG en cáncer de vejiga no músculo-invasivo / Current treatments for BCG failure in non-muscle invasive bladder cancer (NMIBC)

INTRODUCCIÓN: El tratamiento de elección para el cáncer vesical no músculo infiltrante (CVNMI) de alto riesgo es el bacilo de Calmette-Guérin (BCG). Sin embargo, cuando éste falla, el tratamiento indicado es la cistectomía radical. En los últimos años se están desarrollando ensayos con diversos fármacos para evitar esta cirugía en pacientes con fracaso a BCG. El objetivo de este artículo es llevar a cabo una puesta al día de los tratamientos en estudio para la preservación vesical en esta población de pacientes. Material y MÉTODOS: Revisión no sistemática, realizando una búsqueda en PubMed con los términos "Bladder cancer", "Non-muscle invasive bladder cancer", "NMIBC", "BCG", "BCG-refractory", "Mitomycin C", "MMC", "Hyperthermia", "Electromotive Drug Administration", "EMDA" Empleamos los buscadores clinicaltrials.gov y clinicaltrialsregister.eu para localizar ensayos clínicos. RESULTADOS: El único fármaco intravesical aprobado por la Food and Drug Administration (FDA) para carcinoma in situ (CIS) tras fracaso a BCG es la valrubicina. Recientemente la FDA ha aprobado pembrolizumab intravenoso, tras la publicación de los datos preliminares del estudio KEYNOTE-057. Atezolizumab ha demostrado unos resultados preliminares similares de eficacia. En las guías europeas se reconoce como alternativa únicamente la quimiohipertermia inducida por microondas y EMDA-MMC (electromotive drug administration). Otras alternativas en investigación son los taxanos y la gemcitabina, solos o en combinación, los virus recombinantes y la quimiohipertermia intravesical asistida por dispositivos. CONCLUSIONES: Los resultados de los nuevos fármacos son prometedores, con gran número de ensayos en marcha. Conocer los mecanismos de resistencia a BCG es imprescindible para la exploración de nuevas alternativas terapéuticas

INTRODUCTION: The treatment of choice for high-risk non-muscle invasive bladder cancer (NMIBC) is bacillus Calmette-Guérin (BCG). However, when this fails, the indicated treatment is radical cystectomy. In recent years, trials are being developed with various drugs to avoid this surgery in patients with BCG failure. The aim of this article is to update the treatments under study for bladder preservation in this patient population. MATERIAL AND METHODS: Non-systematic review, searching PubMed with the terms "Bladder cancer", "Non-muscle invasive bladder cancer", "NMIBC", "BCG", "BCG-refractory", "Mitomycin C", "MMC", "Hyperthermia", "Electromotive Drug Administration", "EMDA" We used the search engines clinicaltrials.gov and clinicaltrialsregister.eu to find clinical trials. RESULTS: The only intravesical drug approved by the Food and Drug Administration (FDA) for carcinoma in situ (CIS) after failure to BCG is valrubicin. Recently, the FDA has approved intravenous pembrolizumab, following the publication of preliminary data from the KEYNOTE-057 study. Atezolizumab has demonstrated similar preliminary efficacy results. Only microwave-induced chemohyperthermia and EMDA-MMC (electromotive drug administration) are recognized as alternatives in European guidelines. Other options under investigation are taxanes and gemcitabine, alone or in combination, recombinant viruses and device-assisted intravesical chemohyperthermia. CONCLUSIONS: The results of new drugs are promising, with a large number of trials underway. Knowing the mechanisms of resistance to BCG is essential to explore new therapeutic options

Current treatments for BCG failure in non-muscle invasive bladder cancer (NMIBC). / Tratamientos actuales tras fracaso a BCG en cáncer de vejiga no músculo-invasivo.

The treatment of choice for high-risk non-muscle invasive bladder cancer (NMIBC) is bacillus Calmette-Guérin (BCG). However, when this fails, the indicated treatment is radical cystectomy. In recent years, trials are being developed with various drugs to avoid this surgery in patients with BCG failure. The aim of this article is to update the treatments under study for bladder preservation in this patient population. Non-systematic review, searching PubMed with the terms "Bladder cancer", "Non-muscle invasive bladder cancer", "NMIBC", "BCG", "BCG-refractory", "Mitomycin C", "MMC", "Hyperthermia", "Electromotive Drug Administration", "EMDA". We used the search engines clinicaltrials.gov and clinicaltrialsregister.eu to find clinical trials. The only intravesical drug approved by the Food and Drug Administration (FDA) for carcinoma in situ (CIS) after failure to BCG is Valrubicin. Recently, the FDA has approved intravenous Pembrolizumab, following the publication of preliminary data from the KEYNOTE-057 study. Atezolizumab has demonstrated similar preliminary efficacy results. Only microwave-induced chemohyperthermia and EMDA-MMC (Electromotive Drug Administration) are recognized as alternatives in European guidelines. Other options under investigation are taxanes and gemcitabine, alone or in combination, recombinant viruses and device-assisted intravesical chemohyperthermia. The results of new drugs are promising, with a large number of trials underway. Knowing the mechanisms of resistance to BCG is essential to explore new therapeutic options.

Los sistemas de clasificación de la OMS de 1973 y 2004 difieren en la predicción de supervivencia entre los pacientes con cáncer de vejiga en estadio T1 / The 1973 WHO and 2004 WHO grading systems are not equal in prediction of survival among stage T1 bladder cancer patients

Introducción y objetivos: El objetivo de este estudio fue analizar el impacto del grado histológico del tumor en la predicción de supervivencia de los tumores primarios T1 G2 y G3 OMS 1973, que han sido clasificados como HG (alto grado) en el sistema de clasificación OMS 2004. Materiales y métodos: Se revisaron retrospectivamente los datos de 481 pacientes con cáncer de vejiga T1HG primario, tratados entre 1986 y 2016 en 2 centros universitarios. Para comparar los grupos se realizaron pruebas de log-rank y análisis de regresión de Cox. Resultados: Noventa y cinco (19,8%) tumores fueron clasificados como G2 y 386 (80,2%) como G3. La mediana de seguimiento fue de 68 meses. Las tasas de recurrencia y progresión fueron 228 (47,5%) y 109 (22,7%) pacientes, respectivamente. Se realizó cistectomía radical en 114 pacientes (23,7%) y hubo 64 (13,3%) casos de muerte cáncer-específica. La tasa de supervivencia libre de recurrencia para G2, G3 y el total de los pacientes fue del 68,7, el 51,2 y el 56,3%, respectivamente, y la para tasa libre de progresión, se obtuvieron unos valores del 89,3, el 73,2 y el 78,1%. Durante todo el período de seguimiento, los pacientes con tumores G3 obtuvieron peores tasas de supervivencia libre de progresión y de recurrencia que los pacientes con tumores G2. En el análisis multivariante, después del ajuste de las características clínicas, el riesgo de recurrencia y progresión para los tumores G3 fue 1,65 y 2,42 veces mayor que para los tumores G2. Conclusiones: Se demostró que los tumores T1G3 se caracterizan por peores tasas de supervivencia libre de progresión y recurrencia en comparación con los cánceres G2

Introduction and objectives: The aim of this study was to analyse prognostic impact of tumour histological grade on survival differences between primary G2 and G3 WHO1973 stage T1 tumours which were graded as HG according to WHO2004 grading system. Materials and methods: Data from 481 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in 2 university centres were retrospectively reviewed. Log-rank test and Cox regression analysis was performed to compare the groups. Results: 95 (19,8%) tumours were classified as G2 and 386 (80,2%) were G3. Median follow-up was 68 months. The recurrence was observed in 228 (47,5%), and progression in 109 patients (22,7%). Radical cystectomy was performed in 114 pts (23,7%) and there were 64 (13,3%) cancer specific deaths. Recurrence-free rates at 5-years follow-up for G2, G3 and all patients were 68,7%, 51,2% and 56,3% and progression-free rates were 89,3%, 73,2% and 78,1% respectively. For total observation period patients with G3 tumours presented also worse recurrence-free, and progression-free survival levels than patients with G2 tumours. In multivariate analysis, after adjustment for clinical features, the risk of recurrence and progression for G3 tumours was 1,65 and 2,42 fold higher than for G2 tumours. Conclusions: It was shown that G3 T1 tumours are characterized by worse recurrence free and progression free survivals when compared to G2 cancers

Validación de las tablas del grupo CUETO para predecir la recurrencia y progresión del carcinoma urotelial de vejiga T1G3 / Validation of the CUETO scoring model for predicting recurrence and progression in T1G3 urothelial carcinoma of the bladder

Introducción y objetivos: Existen varios estudios con el objetivo de validar las tablas del Club Urológico Español de Tratamiento Oncológico (CUETO). Sin embargo, ninguno de estos estudios se ha centrado en el cáncer de vejiga de alto y muy alto riesgo. El objetivo del presente estudio fue validar externamente el modelo CUETO para predecir la recidiva y la progresión de la enfermedad en el grupo de tumores T1G3 tratados con bacilo Calmette-Guérin (BCG). Pacientes o materiales y métodos: Se analizaron los datos de 414 pacientes con cáncer de vejiga T1G3 primario. Para evaluar la discriminación del modelo se usaron modelos de riesgos proporcionales de Cox y se calcularon los índices de concordancia. Resultados: La mediana de seguimiento fue de 68 meses. Se observó recidiva en 212 (51,2%) y 64 pacientes (15,5%) experimentaron más de un episodio de recurrencia durante el periodo de seguimiento. La progresión del cáncer se observó en 106 pacientes (25,6%), 115 pacientes (27,8%) fueron tratados con cistectomía radical, y hubo 64 (15,5%) muertes por tumor. Para la probabilidad de recidiva y progresión, el índice de concordancia de los modelos CUETO fue de 0,633 y 0,697, respectivamente. Las tablas de CUETO subestimaron significativamente el riesgo de recidiva y marginalmente el riesgo de progresión en el primer año de observación. Durante los 5 años de observación, la tendencia de la recidiva fue mucho menos clara. Por el contrario, hubo una ligera sobreestimación en el riesgo de progresión. El estudio está limitado por su naturaleza retrospectiva. Conclusiones: Se demostró que las tablas de riesgo del grupo CUETO logran una discriminación correcta, tanto para la recidiva de la enfermedad como para la progresión, en pacientes con T1G3 tratados con BCG. El modelo de puntuación (CUETO) subestima el riesgo de recidiva del tumor, pero acierta al predecir el riesgo de progresión

Introduction and objectives: Various studies tried to validate Club Urológico Español de Tratamiento Oncológico (CUETO) tables, yet, none of this papers focused on the high and very high risk bladder cancers. The aim of the study was to externally validate the CUETO model for predicting disease recurrence and progression in group of T1G3 tumors treated with BCG immunotherapy. Patients or materials and methods: Data from 414 patients with primary T1G3 bladder cancer were analysed. To evaluate the model discrimination, Cox proportional hazard regression models were created and concordance indexes were calculated. Results: The median follow-up was 68 months. The recurrence was observed in 212 (51.2%) and 64 patients (15.5%) experienced the recurrence more than once during the study follow-up. Progression of the cancer was observed in 106 patients (25.6%). Radical cystectomy was performed in 115 patients (27.8%) and there were 64 (15.5%) cancer specific deaths. For recurrence and progression probability, the concordance index of the CUETO models was 0.633 and 0.697 respectively. CUETO tables underestimated significantly the risk of recurrence and marginally the risk of progression in the first year of observation. For 5 years of observation, the trend for the recurrence was much less clear. On the contrary, there was slight overestimation in the risk of progression. The study is limited by retrospective nature. Conclusions: It was shown that the CUETO risk tables exhibit a fair discrimination for both disease recurrence and progression in T1G3 patients treated with BCG. CUETO scoring model underestimates the risk of tumor recurrence, but predicts well risk of progression

The 1973 WHO and 2004 WHO grading systems are not equal in prediction of survival among stage T1 bladder cancer patients. / Los sistemas de clasificación de la OMS de 1973 y 2004 difieren en la predicción de supervivencia entre los pacientes con cáncer de vejiga en estadio T1.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyse prognostic impact of tumour histological grade on survival differences between primary G2 and G3 WHO1973 stage T1 tumours which were graded as HG according to WHO2004 grading system. MATERIALS AND METHODS: Data from 481 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in 2university centres were retrospectively reviewed. Log-rank test and Cox regression analysis was performed to compare the groups. RESULTS: 95 (19,8%) tumours were classified as G2 and 386 (80,2%) were G3. Median follow-up was 68 months. The recurrence was observed in 228 (47,5%), and progression in 109 patients (22,7%). Radical cystectomy was performed in 114 pts (23,7%) and there were 64 (13,3%) cancer specific deaths. Recurrence-free rates at 5-years follow-up for G2, G3 and all patients were 68,7%, 51,2% and 56,3% and progression-free rates were 89,3%, 73,2% and 78,1% respectively. For total observation period patients with G3 tumours presented also worse recurrence-free, and progression-free survival levels than patients with G2 tumours. In multivariate analysis, after adjustment for clinical features, the risk of recurrence and progression for G3 tumours was 1,65 and 2,42 fold higher than for G2 tumours. CONCLUSIONS: It was shown that G3 T1 tumours are characterized by worse recurrence free and progression free survivals when compared to G2 cancers.

Validation of the CUETO scoring model for predicting recurrence and progression in T1G3 urothelial carcinoma of the bladder. / Validación de las tablas del grupo CUETO para predecir la recurrencia y progresión del carcinoma urotelial de vejiga T1G3.

INTRODUCTION AND OBJECTIVES: Various studies tried to validate Club Urológico Español de Tratamiento Oncológico (CUETO) tables, yet, none of this papers focused on the high and very high risk bladder cancers. The aim of the study was to externally validate the CUETO model for predicting disease recurrence and progression in group of T1G3 tumors treated with BCG immunotherapy. PATIENTS OR MATERIALS AND METHODS: Data from 414 patients with primary T1G3 bladder cancer were analysed. To evaluate the model discrimination, Cox proportional hazard regression models were created and concordance indexes were calculated. RESULTS: The median follow-up was 68 months. The recurrence was observed in 212 (51.2%) and 64 patients (15.5%) experienced the recurrence more than once during the study follow-up. Progression of the cancer was observed in 106 patients (25.6%). Radical cystectomy was performed in 115 patients (27.8%) and there were 64 (15.5%) cancer specific deaths. For recurrence and progression probability, the concordance index of the CUETO models was 0.633 and 0.697 respectively. CUETO tables underestimated significantly the risk of recurrence and marginally the risk of progression in the first year of observation. For 5 years of observation, the trend for the recurrence was much less clear. On the contrary, there was slight overestimation in the risk of progression. The study is limited by retrospective nature. CONCLUSIONS: It was shown that the CUETO risk tables exhibit a fair discrimination for both disease recurrence and progression in T1G3 patients treated with BCG. CUETO scoring model underestimates the risk of tumor recurrence, but predicts well risk of progression.

El estilo de la comunicación científica / The style of scientific communication

Contexto: La destreza para escribir y la importancia de la calidad de la redacción están sujetas a un cierto menosprecio. Igual que hay guías sobre qué debe constar en cada parte del artículo científico (introducción, material y métodos, resultados y conclusión), existen también "normas" sobre cómo redactarlo. Resultados novedosos solo pueden ser reflejados adecuadamente en un texto formal y estructuralmente correcto. Objetivo: Despertar la conciencia del buen uso del lenguaje en todos los ámbitos profesionales, así como dar algunas recomendaciones prácticas para evitar los errores más frecuentes en nuestro medio. Adquisición de evidencia: Se realizó una búsqueda de los términos "estilo científico", "lenguaje científico" y "cómo escribir un artículo" en las bases de datos de los buscadores Medes, Dialnet e Índice Bibliográfico Español en Ciencias de la Salud (IBECS). Se consultaron también libros sobre la temática. Con ello analizamos las características del estilo científico y los errores más comunes que se observan en los textos científicos. Síntesis de evidencia: Las características del lenguaje científico son: claridad, precisión, brevedad, concisión, fluidez y sencillez. El estilo científico evita, entre otras cosas: frases largas, ausencia de conectores, errores en la sintaxis, la redundancia, barbarismos, extranjerismos, falsos amigos, expresiones coloquiales, cacofonías, jerga, exceso de gerundios, abusar de abreviaturas, usar excesivamente la voz pasiva y errores ortográficos. Conclusiones: Las características principales del estilo científico son la claridad, precisión y brevedad. A escribir artículos se aprende con la práctica, leyendo y con la ayuda de escritores experimentados

Context: Writing skills and the importance of drafting quality are often disregarded. Just as there are guidelines on what each part of a scientific article should comprise (introduction, material and methods, results and conclusion), there are ‘norms’ as to how to draft the article. Novel results can only be appropriately reflected in a formal and structurally correct text. Objective: To raise awareness on the correct use of language in all professional areas, and to provide some practical recommendations to avoid the most common errors in our environment. Evidence acquisition: We performed a search of the terms 'scientific style', 'scientific language' and 'how to write an article' in the databases of the search engines Medes, Dialnet and Índice Bibliográfico Español en Ciencias de la Salud (IBECS). We also consulted books on the subject. We then analysed the characteristics of scientific style and the most common errors observed in scientific texts. Evidence synthesis: The characteristics of scientific language are: clarity, precision, brevity, conciseness, fluidity and simplicity. Scientific style avoids: long sentences, a lack of connectors, syntax errors, redundancies, barbarisms, foreignisms, false friends, colloquial expressions, cacophonies, slang, too many gerunds, too many abbreviations, too much use of the passive voice and spelling mistakes, etc. Conclusions: The principal characteristics of scientific style are clarity, precision and brevity. When we write articles, we learn through practice, reading and the help of experienced writers

The style of scientific communication. / El estilo de la comunicación científica.

CONTEXT: Writing skills and the importance of drafting quality are often disregarded. Just as there are guidelines on what each part of a scientific article should comprise (introduction, material and methods, results and conclusion), there are 'norms' as to how to draft the article. Novel results can only be appropriately reflected in a formal and structurally correct text. OBJECTIVE: To raise awareness on the correct use of language in all professional areas, and to provide some practical recommendations to avoid the most common errors in our environment. EVIDENCE ACQUISITION: We performed a search of the terms 'scientific style', 'scientific language' and 'how to write an article' in the databases of the search engines Medes, Dialnet and Índice Bibliográfico Español en Ciencias de la Salud (IBECS). We also consulted books on the subject. We then analysed the characteristics of scientific style and the most common errors observed in scientific texts. EVIDENCE SYNTHESIS: The characteristics of scientific language are: clarity, precision, brevity, conciseness, fluidity and simplicity. Scientific style avoids: long sentences, a lack of connectors, syntax errors, redundancies, barbarisms, foreignisms, false friends, colloquial expressions, cacophonies, slang, too many gerunds, too many abbreviations, too much use of the passive voice and spelling mistakes, etc. CONCLUSIONS: The principal characteristics of scientific style are clarity, precision and brevity. When we write articles, we learn through practice, reading and the help of experienced writers.

Utilidad clínica de las biopsias aleatorias en el diagnóstico y tratamiento del tumor vesical no-músculo invasivo: revisión sistemática y metaanálisis / Clinical usefulness of random biopsies in diagnosis and treatment of non-muscle invasive bladder cancer: Systematic review and meta-analysis

Introducción y objetivo: Esta revisión sistemática de la literatura se ha focalizado en determinar la utilidad clínica de las biopsias aleatorias (BA) de vejiga para el diagnóstico de carcinoma in situ. Se realizó un metaanálisis para establecer los factores clinicopatológicos asociados a la positividad de dichas biopsias. Adquisición de la evidencia: Se realizó una revisión sistemática de la literatura usando la base de datos PubMed/Medline siguiendo los criterios PRISMA. Se incluyeron 37 artículos, reclutando un total de 12.657 pacientes, de los que 10.975 fueron sometidos a BA. Síntesis de la evidencia La incidencia global de BA positivas fue del 21,91%. Se encontraron diferencias significativas en la positividad de las BA cuando los pacientes fueron estratificados según resultado de la citología, multiplicidad, aspecto tumoral, estadio y grado. Los resultados del metaanálisis revelaron que la presencia de citología positiva, multiplicidad tumoral, tumores de aspecto no papilar, estadio T1 y grados histológicos G2 y G3 representan factores de riesgo que predicen anormalidades en las BA. Conclusiones: La incidencia de BA positivas en pacientes con tumor vesical no-músculo invasivo fue del 21,91%. El máximo rendimiento de estas biopsias se evidencia cuando se realizan de manera normativizada. Los resultados del metaanálisis muestran que, además de la citología positiva y el aspecto no papilar, la multiplicidad tumoral y los grados histológicos G2 y G3 representan factores asociados a BA positivas, por lo que el uso de dichas biopsias se puede hacer extensivo al grupo de riesgo intermedio de la European Organization for Research and Treatment of Cancer (EORTC)

Introduction and objective: This systematic review of the literature has been focused on determining the clinical usefulness of random bladder biopsies (RB) in the diagnosis of carcinoma in situ. A meta-analysis was performed to establish the clinic and pathological factors associated to positive biopsies. Evidence acquisition: A systematic review was performed using Pubmed/Medline database according to the PRISMA guidelines. Thirty-seven articles were included, recruiting a total of 12,657 patients, 10,975 were submitted to RB. Evidence synthesis: The overall incidence of positive RB was 21.91%. Significant differences were found in the incidence of positive RB when patients were stratified according to urine cytology result, tumor multiplicity, tumor appearance, stage and grade. The results of the meta-analysis revealed that the presence of positive cytology, tumor multiplicity, non-papillary appearance tumors, stage T1 and histological grades G2 and G3 represent the risk factors to predict abnormalities in RB. Conclusions: The incidence of positive RB in patients with non-muscle invasive bladder cancer was 21.91%. The maximum usefulness of RB was observed when these are performed in a standardized way. The results of the meta-analysis showed that besides positive cytology and non-papillary appearance tumors, tumor multiplicity and histological grades G2 and G3 represent risk factors associated to positive RB, suggesting that the use of RB might be extensive to the intermediate risk group of the European Organization for Research and Treatment of Cancer (EORTC)