J.M. Gaya

Immediate radical cystectomy vs conservative management for high grade cT1 bladder cancer: is there a survival difference?

Study Type – Aetiology (individual cohort)

Cistectomía radical en tumores vesicales no músculo-infiltrantes que fracasan al tratamiento con bacilo de Calmette-Guérin

Objetivos: evaluar las caracteristicas y evolucion de los pacientes con tumores vesicales no musculo-infiltrantes (TVNMI) sometidos a cistectomia radical por fracaso a la terapia con bacilo de Calmette-Guerin (BCG). Material y metodos: de 864 cistectomias radicales (CR) realizadas en nuestro centro entre 1989 y 2002, 95 (11%) se indicaron en pacientes que habian recibido tratamiento previo con BCG. En 62 casos (65,2%) la CR se realizo por presencia de TVNMI recidivado de alto grado o carcinoma in situ, a pesar del tratamiento con BCG. En 17 de ellos (27%) la pieza de cistectomia mostro un estadio ? pT2. Se considero que estos pacientes fueron infraestadiados. En 33 casos (34,7%) la CR se hizo por progresion clinica a enfermedad musculo-infiltrante (? T2) durante el seguimiento. Analizamos las caracteristicas y evolucion de los pacientes cistectomizados por fracaso a la terapia con BCG y si existian diferencias entre los infraestadiados y los que presentaron progresion clinica durante el seguimiento. Resultados: la supervivencia cancer-especifica a los 5 anos fue del 90% en los 45 casos con estadio clinico y patologico de TVNMI, y del 50,6% en los 50 pacientes con progresion a enfermedad musculo-infiltrante (progresion clinica e infraestadiados) (p < 0,05). No hubo diferencias en la supervivencia entre los pacientes infraestadiados y con progresion clinica. La mediana de tiempo entre el diagnostico del tumor y la progresion fue de 24 meses (percentil 10-90; 6-98 meses).Los pacientes con progresion clinica presentaron de forma significativa mayor proporcion de tumores T1 (p = 0,015) en la RTU previa a la progresion y mas pT3 (p < 0,01) en pieza de CR. Los pacientes infraestadiados tuvieron mas estadios patologicos pT4 (p < 0,02). Conclusiones: en TVNMI de alto riesgo que fracasan a la BCG, la CR debe realizarse antes de la progresion a tumor musculo-infiltrante. Los T1 de alto grado son responsables de la mayor parte de progresiones clinicas y tempranas. Ciertos TVNMI pueden presentar progresion subclinica a traves de la prostata.

[Radical cystectomy in patients with non-muscle invasive bladder cancer who fail BCG therapy].

OBJECTIVE To assess the characteristics and outcomes of patients with non-muscle invasive bladder cancer (NMIBC) undergoing radical cystectomy (RC) due to BCG failure. MATERIALS AND METHODS Ninety-five (11%) of the 864 patients undergoing radical cystectomy (RC) at our center from 1989 to 2002 had received prior treatment with BCG. Of these, 62 (65.2%) underwent RC due to relapsing, high-risk NMIBC or CIS despite BCG therapy. A stage >or= pT2 tumor was reported in the cystectomy specimen in 17 (27%) of these patients, who were considered to have been understaged. RC was performed for clinical progression in 33 patients (34.7%). Their last transurethral resection before RC showed invasive disease. A retrospective analysis was made of the outcomes of patients who underwent RC for BCG failure and the clinical and pathological differences between understaged patients and those with clinical progression. RESULTS Five-year CSS was 90% in 45 patients with clinical and pathological NMIBC and 50.6% in 50 patients with progression to muscle-infiltrating disease (clinical progression and understaged) (p < 0,05). There were no differences in survival in patients with clinical progression as compared to understaged patients. Median time from tumor diagnosis to tumor progression was 24 months (10th-90th percentile, 6-98 months). Patients with clinical progression had significantly more T1 tumors (p = 0.015) in TUR before progression and more pT3 tumors (p < 0.01) in the RC specimen. Understaged patients more often had pathological pT4 stages (p < 0.02). CONCLUSION In patients with high-risk NMIBCs who fail BCG therapy, RC should be performed before progression because survival is decreased when the RC specimen shows muscle-invasive disease. High-grade T1 tumors are responsible for most early clinical progressions. Patients with NMIBC may have subclinical progression, mainly within the prostate.

Current, new and novel therapy for castration-resistant prostate cancer

Androgen deprivation therapy is the standard of care for the initial treatment of metastatic prostate cancer. However, the majority of these patients live long enough to experience disease progression despite castration. This scenario is defined as castration-resistant prostate cancer (CRPC) and has a poor outcome and limited options for treatment. First-line treatment after hormonal therapy failure include secondary hormonal manipulation and docetaxel. Advances in the understanding of the molecular mechanisms underlying CRPC have translated into a recent increase in the number of effective systemic agents, and some of them have been already approved as first and second-line treatment. Despite these advances, the median survival in the first-line setting of metastatic CRPC is approximately 20 months and in the postdocetaxel setting is approximately 15 months. Promising and necessary new therapies in Phase III trials include hormonal agents, new cytotoxics agents, as well as other immunotherapeutics and antiprostate-specific membrane antigen therapies.

Cistoprostatectomía radical robótica: análisis oncológico, funcional y de las complicaciones

OBJECTIVES To review our experience in robot-assisted radical cystectomy, assessing the complications and oncological and functional results. MATERIALS AND METHODS From 2007 to 2014, we performed 67 robot-assisted radical cystectomies combined with lymphadenectomy in 61 cases. The operations were performed on 37 patients due to muscle-invasive tumours and on 30 due to high-risk nonmuscle-invasive tumours. Urinary diversion was conducted extracorporeally, using a Studer neobladder in 47 cases. RESULTS The mean blood loss was 300mL. No case required conversion to open surgery. The median number of lymph nodes extracted was 16 (range 3-33). Pathology revealed 16 pT0, 15 pTis,-pT1-pTa and 44 muscle-invasive tumours, 8 pN+ and 1 with positive margins. The mean hospital stay was 9 days. With a median follow-up of 16 months, 9 (13%) patients were readmitted after the discharge, most for infections associated with the vesical catheter and other catheters. Forty patients (59.7%) presented complications (most were Clavien grade 1-2). There was recurrence during the follow-up in 4 cases (6%), and 4 (5.9%) patients died from cancer. Nineteen (28.3%) patients had complications after 30 days, most of which were urinary tract infections. Of the 47 patients with a neobladder, 45 (96%) had proper daytime continence and 42 (89%) had proper nighttime continence. Ninety percent and 64% of the patients with previously normal sexual function and reduced sexual function, respectively, were able to preserve sexual function with or without drug treatment. CONCLUSIONS Robot-assisted radical cystectomy plus lymphadenectomy, with extracorporeal reconstruction of the urinary diversion, offers good oncological and functional results without increasing the number of complications.

Alloplastic bladder substitution: are we making progress?

Radical cystectomy with lymphadenectomy and urinary diversion is the gold standard treatment for bladder cancer in organ-confined muscle-invasive disease and selected patients who have high-grade non-muscle-invasive disease or are non-responders to BCG. The main and most morbid complications of this challenging surgery are related to the use of bowel for urinary tract reconstruction. For this reason, many past projects were devoted to finding an alternative to the use of bowel. The aim of this review is to provide a summary of the evolution of alloplastic bladder substitution. A comprehensive review of the literature was performed using the Medline National Library of Medicine database and Google Scholar. Keywords used were cystectomy and intestine/bowel, replacement, bladder substitution, organ replacement, artificial bladder, alloplastic material, biomaterial, and tissue engineering. Various prostheses have been proposed for replacement of the urinary bladder, silicone being the most frequently used material. The first published model of an alloplastic bladder was described by Bogash et al. in late 1959, while the last, in 1996, was suggested by Rohrmann. Interprofessional collaboration, recent advances in technology, and tissue engineering may help in developing suitable bladder prostheses. Urologists as well as engineers and the industry need to give this matter serious attention.

Laparoscopic Management of Ureteroileal Anastomosis Strictures: Initial Experience

BACKGROUND A ureteroileal anastomosis stricture (UAS) is one of the most frequent complications after radical cystectomy. Open surgical repair is the treatment of choice but is associated with morbidity. OBJECTIVE To describe the efficacy and safety of laparoscopic management for benign secondary UAS. DESIGN, SETTING, AND PARTICIPANTS A review was performed of the 11 initial procedures performed at our academic center from December 2010 to December 2014, with mean follow-up of 38 mo (range 12-169). Patients included had benign ureteroileal strictures longer than 1cm. SURGICAL PROCEDURE A pure laparoscopic approach was systematically used, involving a two-step procedure for left and a one-step procedure for right ureteral stenosis. MEASUREMENTS Perioperative data were collected and complications were assessed using the Clavien-Dindo grading system. Outcomes and follow-up data were analyzed. RESULTS AND LIMITATIONS A descriptive statistical analysis was performed for 11 surgeries in ten patients. The median stricture length was 2.4cm. No conversion to open surgery was required. The mean blood loss was 180ml and the mean hospital stay was 10 d. Early complications included limited lymphorrhea (n=1), limited anastomotic leakage (n=2), and accidental descent of a ureteral catheter (n=1) that was replaced with radiologic intervention. The mean follow-up was 38 mo (range 12-169). No late complications were reported. After 1 yr of follow-up, six patients had good glomerular filtration rates, all patients were asymptomatic, and no stenotic relapses were detected. CONCLUSIONS This laparoscopic technique for the management of benign secondary UAS is feasible, with good results and without long-term complications. This minimally invasive approach reduces the morbidity associated with open surgery while retaining good success rates. PATIENT SUMMARY We describe a novel laparoscopic approach for patients with a ureteroileal anastomosis stricture after radical cystectomy to avoid the complications associated with open surgery. The surgery was found to be viable and safe with good long-term results.

Prospective evaluation of the performances of narrow-band imaging flexible videoscopy relative to white-light imaging flexible videoscopy, in patients scheduled for transurethral resection of a primary NMIBC

PurposeTo evaluate on a lesion-by-lesion basis Narrow-Band Imaging flexible videoscopy (NBI-FV) in the detection of cancer compared to White-Light Imaging flexible videoscopy (WLI-FV).MethodsWLI-FV and NBI-FV were sequentially performed in patients scheduled for TURBT for primary bladder cancer. Suspicious findings were individually harvested and characterized under WLI-FV (suspicious/non-suspicious) and NBI-FV (5-point Likert scale) and pathology. The primary objective was to determine if NBI-FV informed at least 20% more cancer lesions than WLI-FV (Relative true-positive rate > 1.19). A minimum of 120 specimens was to be analyzed to reach 90% power.ResultsOf 147 specimens taken in 68 patients, 101 were found suspicious under WLI-FV and 64 (64/101, 63.4%) confirmed as cancer. Of the 46 lesions undetected by WLI-VF, 16 were found positive for cancer (16/46, 34.8%). For NBI-FV, a significant increase in positive samples was observed with increments in Likert scale (p < 0.0002). Relative true-positive rate was 1.22 (95% CI 1.12–1.39)—NBI-FV detected 22% more cancer lesions compared to WLI-FV. Relative false-positive rate was 1.35 (95% CI 1.19–1.59).ConclusionResearching alterations in mucosa and microvasculature by narrow-band imaging flexible videoscopy augmented by 22% the detection of cancer foci and contributed to the objective of complete resection of all visible lesions. Conversely, it entailed a 35% increase in false-positive results compared to white-light imaging, although the structured analysis of narrow-band imaging findings might be used to grade suspicion according to the Likert scale and balance the risk of a false-positive result to the benefit of demonstrating cancer.

PD7-10 TURBT OF THE INTRAMURAL PORTION OF THE DISTAL URETER: PREDICTIVE FACTORS FOR SECONDARY STENOSIS AND DEVELOPMENT OF UPPER URINARY TRACT TUMOURS

INTRODUCTION AND OBJECTIVES: It is unusual to diagnose a urothelial cell carcinoma in the intramural ureter based on the visualization of papillae in the ureteral meatus or as an incidental finding during the transurethral resection of a bladder tumour (TURBT) adjacent to the ureteral meatus. We analyse the incidence of stenosis and upper urinary tract tumours (UTUC) after TURBT/excision of the intramural portion of the distal ureter and/or bladder cancer. METHODS: 112 patients, with a mean age of 69.3 13 years and a mean follow-up of 56 4 months, underwent TUR of the intramuralureter and were diagnosed with non-muscle-invasive bladder cancer (NMIBC) at that location: 58% of cases were concomitant with primary tumours. The TUR specimen of the ureteral meatus was always sent separately for histological analysis. In patients with apparent tumour remaining in the distal ureter, ureterorenoscopy was performed at 3e4 months. A double J catheter was left in patients undergoing extensive resection of the trigone area (32.1%). 22.3% and 75.9% of patients received mitomycin and BCG respectively. RESULTS: Pathological examination revealed Ta in 64%, T1 in 22.3% and CIS in 17%.17 patients (15.2%) developed UTUC, which was located in the distal ureter in 65.4%, and 13 (11.6%) a distal ureteral stenosis. The presence of a ureteral catheter did not influence the outcome (23% vs 33%, p1⁄40.45). In univariate analysis, statistically significant differences were observed between primary and recurrent tumours with respect to the incidence of symptoms (60% vs 26%, p 3 cm were associated with a higher likelihood of development of distal ureteral stenosis and CIS of the intramural portion increased the risk of UTUC. Closer follow-up of should be undertaken since these factors are associated with a higher incidence of upper urinary tract problems.

Urothelial Carcinoma In Situ: Concerns About Daily Practice

This systematic review in this month’s issue of European Urology offers a very good overview of the diagnosis and management of carcinoma in situ (CIS) of the lower urinary tract [1]. Since CIS of the bladder was identified as a flat, highgrade lesion confined to the mucosa, we have learned much about its natural history, diagnosis, and management; however, some aspects of understanding and treatment still need to be improved to detect and obtain better results for our patients. CIS of the bladder is commonly associated with highgrade bladder disease, both non–muscle invasive and muscle invasive, but it can also be associated with lowgrade disease [2]. In non–muscle-invasive disease, approximately 45–71% of patients are disease free after intravesical bacillus Calmette-Guerin (BCG) treatment, and the rate of progression to muscle-invasive disease is 14–22% [3]. There are important discrepancies in data on the incidence of CIS in primary non–muscle-invasive bladder cancer (NMIBC). According to the European Organisation for Research and Treatment of Cancer (EORTC), the incidence is 1500 patients with primary NMIBC, all of whom underwent multiple bladder biopsies, the incidence of CIS was 19% [2]. The same group observed a 15% incidence of CIS for the period from 2000 to 2008 (unpubl. data). There are no published data on the variation in incidence among areas or onwhich factors may influence the differences, but it remains the case that whenever multiple biopsies of the bladder are routinely done, the incidence is higher and may influence clinical decision making. According to the international guidelines, mapping or random bladder biopsies are not routinely recommended in patients with TaT1 tumors because of the low likelihood of detecting CIS unless there is positive cytology or suspicious areas in the bladder [4]. The discrepancies regarding the incidence may arise from various sources, including whether preoperative urinary cytology is routinely performed, the nature of the population studied, the presence of local risk factors, whether multiple biopsies of the bladder are routinely performed to search for CIS, whether adjuvant tools are used in the diagnosis (photodynamic diagnosis) [4], and differences in pathologist or uropathologist interpretation. Thorstenson et al [5] presented their results in a series of 538 patients, 61% of whom underwent multiple bladder biopsies. Among the latter patients, 14% were diagnosed as having concomitant CIS. Ultimately, better results were obtained in this subgroup of patients because most of them received BCG or upfront cystectomy. It may be concluded that this subgroup had better cancer-specific survival because of the knowledge that CIS was present. Good communication between urologists and pathologists is important to evaluate results regarding the detection of CIS in their own series; it has been demonstrated in bladder cancer that the staging results may vary when evaluation is performed by referral to uropathologists [6]. Urologists should always request urinary cytology before transurethral resection (TUR) of a primary tumor; if cytology is positive, theymust proceed tomultiple biopsies, including of the prostatic urethra [4]. This should also be done when suspicious areas are seen during TUR of bladder tumor. The classification of CIS, which is useful to determine some distinct groups, is not really relevant to clinical decision making, even though various studies have shown concurrent CIS to have a worse prognosis than primary CIS. In a series of 90 patients with CIS, Meijer et al [3] reported a EU RO P E AN URO L OG Y 6 7 ( 2 0 1 5 ) 8 8 9 – 8 9 0