Randomized clinical trial on the use of IMAGE1 S LIGHT (SPIES) vs. white light in the prevention of recurrence during transurethral resection of bladder tumors: Analysis after 12-month follow-up.

INTRODUCTION: The improved image resolution of IMAGE1 S technology will increase tumor detection, achieve a greater number of complete resections, and would probably have an impact on the reduction of recurrences. AIM: The primary objective was to compare the recurrence rates of IMAGE1 S vs. white light during transurethral resection of the bladder (TUR); the secondary objective was to compare the complication rates according to Clavien-Dindo (CD) at 12 months of follow-up. METHODS: Prospective, randomized 1:1, blinded clinical trial. Recurrence and complication rates according to CD were analyzed using chi-square/U Mann-Whitney tests and recurrence-free survival (RFS) using Kaplan-Meier curves. The European Association of Urology (EAU) 2021 scoring model was used. RESULTS: The analysis included 103 participants; 49 were assigned to the IMAGE1 S group and 54 to the white light group. Recurrence rates were 12.2% and 25.9%, respectively (P = .080). The low and intermediate risk group had a lower recurrence rate with IMAGE1 S (7.7% vs. 30.8%, P = .003) and a higher RFS with IMAGE1 S (85.2% vs. 62.8% Log Rank: 0.021), with a Hazard Ratio of 0.215 (95% CI: 0.046-0.925). No differences were observed in the high and very high-risk groups. Complications were mostly grade I and rates were similar between both groups (IMAGE1 S 20.4% vs. white light 7.4% P = .083). CONCLUSIONS: There were no differences in the recurrence rates between groups. However, the low and intermediate risk group had a lower recurrence rate with IMAGE1 S. In addition, perioperative complication rates were not higher.

Revisión sistemática y metaanálisis sobre CK20, CD44, Ki67 y p53 como marcadores inmunohistoquímicos en el carcinoma in situ vesical / A systematic review and meta-analysis of CK20, CD44, Ki67 and p53 as immunohistochemical markers in bladder carcinoma in situ

Introducción: La displasia urotelial y el carcinoma in situ (CIS) están relacionados con la recurrencia y la progresión del carcinoma urotelial. Diferenciar el CIS y la displasia de la atipia reactiva suele ser difícil sobre la base de las características histológicas. La integración de los hallazgos histológicos con la inmunohistoquímica se utiliza en la práctica habitual para realizar el diagnóstico del CIS y, para ello, se utilizan los marcadores inmunohistoquímicos CK20, CD44, Ki67 y p53 como complemento al estudio histológico.En este trabajo, nos propusimos evaluar CK20, CD44, Ki67 y p53 como marcadores inmunohistoquímicos en pacientes con CIS, mediante una revisión sistemática y un metaanálisis.Materiales y métodosSe realizó una revisión sistemática con búsqueda en bases de datos electrónicas de estudios en inglés publicados desde enero de 2010 hasta abril de 2021. Se consideraron elegibles los estudios que evaluaban la expresión de CK20, CD44, Ki67 y p53 en el CIS.ResultadosEn total, 15 referencias fueron aptas para la revisión cuantitativa. La tasa global de expresión de CK20, CD44, Ki67 y p53 en el CIS fue del 43%, 31%, 44% y 38%, respectivamente.ConclusionesNuestro estudio apoya el consenso de la Sociedad Internacional de Patología Urológica de 2014 sobre la evaluación histológica como método de referencia para diagnosticar el CIS urotelial, y sugiere que una correlación muy estrecha entre los datos morfológicos, inmunohistoquímicos y clínicos es esencial para proporcionar el mejor manejo de los pacientes con carcinoma vesical. (AU)

Introduction: Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology.In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis.Materials and methodsA systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS.ResultsIn total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively.ConclusionsOur study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma. (AU)

A systematic review and meta-analysis of CK20, CD44, Ki67 and p53 as immunohistochemical markers in bladder carcinoma in situ.

BACKGROUND: Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology. In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis. MATERIALS AND METHODS: A systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS. RESULTS: In total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively. CONCLUSIONS: Our study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma.

The benefit of a neoadjuvant instillation of chemotherapy in non-muscle invasive bladder cancer: Interim analysis of the PRECAVE randomized clinical trial. / El beneficio de una instilación neoadyuvante de quimioterapia en el carcinoma vesical no músculo invasivo: análisis intermedio del ensayo clínico aleatorizado PRECAVE.

OBJECTIVE: Although an immediate postoperative instillation of chemotherapy (IPOIC) after transurethral resection of bladder tumors (TURBT) is recommended for the prevention of recurrences of non-muscleinvasive bladder cancer (NMIBC), evidence shows there is an important compliance failure worldwide. We believe that an immediate neoadjuvant instillation of chemotherapy (INAIC) can act similarly, reducing the recurrence risk of NMIBC. Here we present the interim analysis of the PRECAVE clinical trial. MATERIAL AND METHODS: Patients with clinically diagnosed NMIBC were randomized to receive an INAIC with mitomycin C before TURBT (Group A) or to a control group with TURBT only (Group B). Primary end point was to compare the efficacy of an INAIC in the early recurrence-free survival (RFS). Secondary end points were: RFS in patients who did not receive adjuvant treatments, toxicity, and feasibility. RESULTS: A total of 124 patients with Ta/T1 G1-G3NMIBC were included in the initial analysis (Group A:64, Group B: 60). Demographics, risk classification, complications, and adjuvant treatments were balanced between groups. Eighty-four patients (Group A: 45, Group B: 39) who completed a one-year follow-up were included in the efficacy analysis and no difference was observed in the RFS between groups (p=0.3). In the subgroup of patients who did not receive adjuvant treatments, we found a significant difference in favor of an INAIC (p=0.009) and an 80% reduction in the risk of early recurrences (Hazard Ratio: 0.20; 95% confidence interval: 0.05-0.81; p=0.0024). No differences were observed in adverse events. Only 4 patients did not receive an INAIC despite being planned. CONCLUSIONS: In this interim analysis, although we could not demonstrate a reduction in the RFS of all patients, we did find a significant decrease of recurrences in patients who did not receive adjuvant treatments. The administration of an INAIC seems to be safe and our protocol appears feasible and reproductive.

OBJETIVO: Aunque el uso de una instilación postoperatoria inmediata de quimioterapia (IPOIQ) tras una resección transuretral vesical (RTUV) esta recomendada para prevenir recurrencias de carcinoma vesical no músculo invasivo (CVNMI), no se llega a realizar en muchos casos debido a fallos en su cumplimiento. Nosotros creemos que una instilación neoadyuvante inmediata de quimioterapia (INAIQ) puede actuar de manera similar reduciendo el riesgo de recurrencias. Presentamos el análisis intermedio del ensayo clínico PRECAVE.MATERIAL Y MÉTODOS: Se aleatorizó a pacientes diagnosticados de CVNMI a recibir una INAIQ con mitomicina C antes de la RTUV (Grupo A) o a un grupo control con RTUV solamente (Grupo B). El objetivo primario fue comparar la eficacia de una INAIQ en la supervivencia libre de recurrencia (SLR) temprana. Los objetivos secundarios fueron la SLR en pacientes que no recibieron tratamientos adyuvantes, toxicidad y viabilidad. RESULTADOS: Analizamos un total de 124 pacientes con CVNMI Ta/T1G1-G3 fueron analizados (Grupo A:64, Grupo B: 60). No se encontraron diferencias entre datos demográficos, grupos de riesgo, complicaciones o tratamientos adyuvantes. Para el análisis de eficacias e incluyeron 84 pacientes (Grupo A: 45, Grupo B:39) con al menos un año de seguimiento, sin observar diferencias en la SLR (p=0,3). Sin embargo, en el subgrupo que no recibió tratamientos adyuvantes, sí encontramos una diferencia significativa a favor de la INAIQ (p=0,009), y una reducción del riesgo de recurrencias tempranas del 80% (Hazard Ratio: 0,20; intervalo de confianza 95%: 0,05-0,81; p=0,0024). No se observaron diferencias en la aparición de eventos adversos. Solo 4 pacientes no recibieron un INAIC a pesar de estar planificado. CONCLUSIONES: En este análisis intermedio, aunque no pudimos demostrar una reducción en la SLR de todos los pacientes, sí encontramos una diferencia en el subgrupo que no recibió tratamientos adyuvantes. La administración de una INAIC parece ser segura, y nuestro protocolo parece factible y reproducible.

The nested variant of bladder transitional cell carcinoma: Review of 12 cases and review of the literature.

OBJECTIVES: The nested variant of bladder transitional cell carcinoma is extremely rare and has a different biological behavior to other bladder tumors. The aim of this study is to analize if their behavior is as aggressive as has been described in the literature. MATERIAL AND METHOD: Review of 12 diagnosed cases with nested variant of bladder transitional cell carcinoma and analysis of demographic characteristics, clinical presentation, tumor characteristics, treatment options, analysis of recurrence and cancer-specific survival between January 1997 and December 2010 in our hospital. RESULTS: 50% of the cases had a pathologic stage ≥T2, with grade of differentiation G2 (50%) or G3 (50%). After the pathological result of the TUR (transurethral resection) Bladder, 5 cases underwent radical cystoprostatectomy, 3 a second TUR bladder and 4 cases with treatment chemotherapy and/or radiotherapy (RT). Five out of 12 cases (41.7%) died due to bladder cancer and 3 died (25%) of other causes (urinary sepsis, respiratory failure, renal failure). With a median follow up of 40 months, the overall survival was 50% and cancer-specific survival of 65.6%. CONCLUSIONS: The nested variant of bladder transitional cell carcinoma is a disease with an advanced-stage presentation, with high recurrence and mortality rates despite the use of different treatments. So far there is not a clinical practice guideline for this variety of urothelial tumor.