S.M. Di Stasi

Are referral centers for non-muscle-invasive bladder cancer compliant to EAU guidelines? A report from the vesical antiblastic therapy Italian study.

Introduction: Adherence to international guidelines is viewed as a prerequisite for optimal medical care delivery. Previously reported surveys for non-muscle-invasive bladder cancer (NMIBC) employed mailed questionnaires to urologists or patients resulting in conflicting degrees of agreement with existing guidelines. In the current study, contemporary information on the management of NMIBC was generated from a sample of Italian centers. Patients and Methods: Eight Italian referral centers for the treatment of NMIBC were asked to collect information relative to all consecutive patients with a histology-proven NMIBC undergoing a transurethral resection from January 1 to March 31, 2009. The primary study objective was to verify the level of adherence of disease management with European guidelines. Results: 344 patients resulted in being evaluable. 49.2% of high-risk patients underwent a repeat transurethral resection. Bacillus Calmette-Guérin was employed in 35% of cases, while chemotherapy was in 22%. An early single regimen was adopted in 136 patients and only in 1 out of 3 low-risk patients. High-risk NMIBC received bacillus Calmette-Guérin and chemotherapy as first-line therapy in 66 and 12.5% respectively. After 3 months, cystoscopy had been reported for 82.5% of patients with a recurrence rate of 13%. Conclusion: Adherence of Italian Institutions to EAU guidelines was optimal when reporting baseline variables. Significant degrees of discrepancy emerged in treatment choices.

1001 The impact of re-TUR on clinical outcomes in a large cohort of t1g3 patients treated with BCG

INTRODUCTION AND OBJECTIVES: Low risk non-muscle invasive bladder cancer (NMIBC) is an heterogeneous neoplasm, characterized by a high percentage of recurrences but a low tendency of progression. In this group of patients, overtreatment posts and impact in the quality of life and it implies high significant economical costs and an important deterioration of the quality of life, without evidence of improving their survival. Therefore, it seems reasonable to develop a program based on surveillance and monitoring of new recurrences. Our aim is to report our experience with low-risk bladder cancer patients under an active surveillance program after cancer recurrence, and to analyse which variables might help to predict progression. METHODS: From 2006 we have offered the option of active surveillance to all low risk tumours at time of recurrence. Follow-up included flexible cystoscopy and cytology every six months. TUR was performed when tumour size or number of lesions increased, at high grade cytology, when hematuria, tumour aspect worsened or patients’ choice. RESULTS: 68 patients were included. Mean age at recurrence was 71.5 years. Only 13,2% were female. Almost all patients received immediate postoperative mytomicin C (96%). Histological initial features were stage pTa in 48.5%, stage pT1a in 25%, pTx in 7.4% and PUNLMP in 17.6%; all were low grade. Mean time between TUR and recurrence was 33 months. The mean follow-up was 25,8 months. 32 (47%) patients underwent TUR after recurrence (mean time 20 months). Main cause of TUR (50%) was the increase of the number of lesions and tumor size, 18% due to hematuria, 6% to positive citology. Concerning recurrence features, 80% were single tumors and size was 5 mm in 60%. Seven patients (21.87%) progressed in stage (pTa to pT1a) (4) or grade (3). All patients with progression, tumor size was 5 mm or had positive cytology. None of our patients progressed to muscle invasive bladder cancer. CONCLUSIONS: Patients with recurrent, small, non muscleinvasive bladder tumours can be safely offered monitoring under an active surveillance protocol. Active surveillance can be safely considered in patients with less than 5mm recurrence or negative cytology.

Prognostic factors and risk groups in T1G3 patients initially treated with BCG: Results of a multicenter retrospective series in 1743 patients

Prognostic Factors And Risk Groups In T1g3 Patients Initially Treated With Bcg : Results Of A Multicenter Retrospective Series In 1743 Patients

Recurrence and progression according to stage at re-TUR in t1g3 bladder cancer patients treated with BCG: Not as bad as previously thought

INTRODUCTION AND OBJECTIVES: Intravesical induction immunotherapy with Bacille Calmette-Guerin (BCG) is the standard of care treatment for high risk non-muscle invasive bladder cancer (NMIBC). Despite this, rates of recurrence and progression to muscleinvasion remain unacceptably high. We sought to optimize immunologic response to intravesical induction immunotherapy with standardized BCG intradermal vaccination prior to induction, and herein report our two year outcomes. METHODS: BCG-naive patients with high-risk NMIBC who were candidates for BCG therapy were prospectively enrolled from 2014-2015. Patients who were PPD-negative were subsequently vaccinated with BCG in standard intradermal fashion, and 3 weeks later, standard induction immunotherapy with Tice BCG was performed. Urinary cytokines, BCG-specific T and mononuclear cells, and clinical outcomes were analyzed. RESULTS: 15 patients were enrolled and 13 completed the study; 5 controls were also enrolled. The median follow-up was 20.4 months (range: 28.1 to 14.8m). No patient experienced dose-limiting toxicity or a Grade 3+ adverse event. No patients progressed to muscleinvasive disease. 9 patients successfully converted PPD. 9 of 13 patients recurred in the lower tract (69.2%) and all were successfully salvaged. Immunologically, BCG-specific T cell lymphoproliferation was increased, as was IFN-g secretion, IFN-g ELISPOT response, and direct ex vivo IFN-g response. Flow cytometry demonstrated that BCG significantly enhanced CD4+ and CD8+ T cells in most patients. Compared to controls, primed patients exhibited an increase in IFN-g release in response to BCG ex vivo at both 3 months and 6 months after therapy. Priming resulted in an earlier and more robust increase in urinary IL-2, IL-17, and IL-8 compared to control patients suggesting a potential benefit from earlier and higher activation of local immune response. CONCLUSIONS: Vaccination with BCG prior to induction immunotherapy results in improved immunologic measurements and increased urinary cytokines associated with control of high-risk NMIBC. Priming may represent a method to increase the efficacy of BCG immunotherapy for high-risk NMIBC. Further study with dedicated multicenter clinical trials and long term follow-up is warranted.

BOTULINUM A TOXIN INTRAVESICAL INJECTIONS IN THE TREATMENT OF PAINFUL BLADDER SYNDROME: A PILOT STUDY

OBJECTIVE We evaluated the efficacy and tolerability of botulinum A toxin (BTX-A) intravesical injections in patients affected by painful bladder syndrome with increased urinary frequency, refractory to conventional treatment modalities. METHODS Twelve women and two men were prospectively included in the study. Under short general anaesthesia patients were given injections of 200 U of commercially available BTX-A diluted in 20 ml 0.9% NaCl. Injections were performed submucosally in the trigone and bladder floor under cystoscopic control. Voiding chart, the Visual Analog Scale (VAS) for pain, and urodynamics were performed before treatment and 1 and 3 mo afterward. RESULTS Overall, 12 patients (85.7%) reported subjective improvement at 1 and 3 mo follow-up. The mean VAS score was significantly reduced at 1 and 3 mo after treatment (p<0.05 for both); at the same time points daytime and nighttime urinary frequency significantly decreased (p<0.01 and p<0.05, respectively), and bladder cystometric capacity significantly increased (p<0.01). Two patients reported incomplete bladder emptying. We did not detect any systemic side effects during or after treatment. CONCLUSIONS The results of this pilot study indicate that BTX-A intravesical injections are effective in the short-term management of painful bladder syndrome. By modulating afferent C-fiber activity within the bladder walls, BTX-A significantly improves urodynamic parameters and reduces bladder pain and urinary frequency.

Long term follow up of resiniferatoxin intravesical administration in the treatment of detrusor hyperreflexia in spinal cord injured patients

MATERIAL & METHODS: Eleven patients were included in this prospective study. After a basal evaluation with urodynamics and the frequency of daily incontinent episodes, patients received intravesical administrations of RTX 0.6 mM in 50 ml of normal saline. RTX instillations were repeated when there was recurrence of urinary symptoms and/or urodynamic worsening. Uninhibited detrusor contractions (UDC) threshold and maximum pressure, and maximum bladder capacity were measured at baseline and during follow up. The frequency of daily incontinent episodes was recorded by means of a voiding diary. Local or systemic side effects were also noted.