A Feasibility Study to Evaluate Changes in Urinary Metabolites after OnabotulinumtoxinA Injection for Refractory Overactive Bladder.

Metabolomics analysis of urine before and after overactive bladder (OAB) treatment may demonstrate a unique molecular profile, allowing predictions of responses to treatment. This feasibility study aimed to correlate changes in urinary metabolome with changes in OAB symptoms after intravesical onabotulinumtoxinA (BTX-A) injections for refractory OAB. Women 18 years or older with non-neurogenic refractory OAB were recruited to complete OAB-V8 questionnaires and submit urine samples before and after 100 units intravesical BTX-A injection. Samples were submitted to CE-TOFMS metabolomics profiling. Data were expressed as percent of change from pre-treatment and were correlated with OAB-V8 score improvement. Urinary metabolite changes in the OAB-V8 groups were compared using the Kruskal-Wallis test, and associations between metabolites and OAB-V8 scores were examined using quantile regression analysis. Of 61 urinary metabolites commonly detected before and after BTX-A, there was a statistically significant decrease in adenosine and an increase in N8-acetylspermidine and guanidinoacetic acid levels associated with OAB score improvement, suggesting that intravesical BTX-A injection modifies the urinary metabolome. These urinary metabolites could provide insight into OAB pathophysiology and help identify patients who would benefit most from chemodenervation.

Trends in Mesh Use for Pelvic Organ Prolapse Repair From the Medicare Database.

OBJECTIVE: To investigate recent trends in mesh use for pelvic organ prolapse (POP)-related reconstruction procedures. MATERIALS AND METHODS: Using the 2001-2011 5% Medicare claims database, we identified POP diagnoses and related procedures. Transvaginal mesh use and sacrocolpopexy were first reported in 2005 and 2004, respectively. RESULTS: A total of 613,160 cases of vaginal and abdominal POP repair procedures were identified. The majority of procedures involved multiple compartments. The rate of mesh use increased dramatically from 2% of repairs in 2005 to 35% by 2008. After the Food and Drug Administration warning in 2008, mesh use plateaued and then decreased in 2011. Mesh was used more commonly in younger (odds ratio [OR] 0.722, P < .001), white (OR 0.712-0.791 for other races, P < .001) women in the South (OR 0.741-0.848 for non-South regions, P < .001). Starting in 2008, the rate of sacrocolpopexy procedures almost doubled yearly until 2011. Sacrocolpopexy was more common in younger patients (49% in women <70 years) and in white women (88%); the majority of sacrocolpopexies were performed in the South (60%) and laparoscopically (83%-98%). CONCLUSION: The treatment of POP has changed over time. The use of mesh increased significantly until 2008, after which it plateaued following the Food and Drug Administration warning regarding mesh-related complications. Concurrently, the number of sacrocolpopexy procedures increased significantly starting in 2008 as the use of laparoscopic and/or robotic technique and concern regarding transvaginal mesh increased.

Disparities in the Use of Sacral Neuromodulation among Medicare Beneficiaries.

PURPOSE: Sacral neuromodulation with the InterStim® has been done to treat urinary and bowel control. There are limited data in the literature on use trends of sacral neuromodulation. We explored disparities in use among Medicare beneficiaries. MATERIALS AND METHODS: We queried a 5% national random sample of Medicare claims for 2001, 2004, 2007 and 2010. All patients with an ICD-9 diagnosis code representing a potential urological indication for sacral neuromodulation were included. Patients who underwent device implantation were identified using CPT-4 codes. Statistical analysis was done with the chi-square and Fisher tests, and multivariate logistic regression using software. RESULTS: A total of 2,322,060 patients were identified with a diagnosis that could potentially be treated with sacral neuromodulation. During the 10-year study period the percent of these patients who ultimately underwent implantation increased from 0.03% to 0.91% (p <0.0001) for a total of 13,360 (0.58%). On logistic regression analysis women (OR 3.85, p <0.0001) and patients younger than 65 years (OR 1.00 vs 0.29 to 0.39, p <0.0001) were more likely to be treated. Minority patients (OR 0.38, p <0.0001) and those living in the western United States (OR 0.52, p <0.0001) were less likely to receive treatment. CONCLUSIONS: Sacral neuromodulation use significantly increased among Medicare beneficiaries in a 10-year period. Patients were more likely to be treated with sacral neuromodulation if they were female, white, younger (younger than 65 years) and living outside the western United States.

Renal calculi: trends in the utilization of shockwave lithotripsy and ureteroscopy.

INTRODUCTION: To assess trends in the usage of extracorporeal shockwave lithotripsy (SWL) and ureteroscopy (URS) in the treatment of renal calculi. MATERIALS AND METHODS: An analysis of the 5% Medicare Public Use Files (years 2001, 2004, 2007 and 2010) was performed to evaluate changes in the use of SWL and URS to treat renal calculi. Patients were identified using ICD-9 (cm) and CPT codes. Statistical analyses, including the Fisher, 2 tests, and multivariate logistic regression analysis were performed using SAS 9.3 (SAS Institute Inc., Cary, NC, USA) and SPSS v20 (IBM Corp., Armonk, NY, USA). RESULTS: The absolute number of patients diagnosed with (+85.1%) and treated for (+31.5%) kidney calculi increased from 2001 to 2010. The ratio of diagnosed/treated patients declined from 15.2% in 2001 to 10.8% in 2010. Whites (OR = 1.27, p < 0.0001), patients in the South (OR = 1.16, p < 0.0001) and those ≤ 84 years of age were more likely to be treated. The utilization of SWL (84.7%) was greater than URS (15.3%), but the utilization of URS increased over time from 8.4% in 2001 to 20.6% of cases by 2010 (p < 0.0001). Treatment via URS was more likely in women (OR = 1.28, p < 0.0001), in patients living outside the South (OR = 1.29-1.45, p ≤ 0.006) and in later years of the study (OR = 2.87, p < 0.0001). CONCLUSIONS: Treatment patterns for renal calculi changed from 2001 to 2010. The usage of URS increased at the cost of SWL. Multiple sociodemographic factors correlated with the likelihood of being treated surgically as well as the choice of the surgical approach.

A meta-analysis of the performance of retropubic mid urethral slings versus transobturator mid urethral slings.

PURPOSE: We evaluate the efficacy and complications after retropubic and transobturator mid urethral slings in the treatment of female stress urinary incontinence. MATERIALS AND METHODS: A systematic literature review was performed using MEDLINE®, limited to randomized controlled trials with a minimum followup of 1 year and type 1 grafts. Statistical analyses were performed using StatsDirect Version 2.7.9 (StatsDirect Ltd, Altrincham, UK). RESULTS: Retropubic mid urethral sling procedures showed statistically significant improvements in objective cure (OR 1.35, 95% CI 1.10-1.67, p=0.005) and subjective cure (OR 1.24, 95% CI 1.04-1.49, p=0.02). Bladder perforations (OR 5.72, CI 2.94-11.12, p <0.0001) and bleeding (OR 2.65, CI 1.54-4.59, p=0.0005) were significantly more common with retropubic mid urethral slings, whereas vaginal perforations (OR 0.29, CI 0.15-0.56, p=0.0002) and neurological symptoms (OR 0.35, CI 0.25-0.5, p <0.0001) were more common with transobturator mid urethral slings. Operative time was significantly longer for retropubic mid urethral slings than transobturator mid urethral slings (OR 1.38, p <0.0001). No significant differences were noted in mesh erosions and exposure, urinary retention, infection, lower urinary tract symptoms and length of hospital stay. CONCLUSIONS: Retropubic mid urethral slings showed better objective and subjective cure rates than transobturator mid urethral slings. However, bladder perforation and bleeding were more common with retropubic mid urethral slings. Operative time was longer for retropubic mid urethral slings. Transobturator mid urethral slings were associated with more cases of neurological symptoms and vaginal perforation.

Image-based simulation of urethral distensibility and flow resistance as a function of pelvic floor anatomy.

AIMS: The goal of this study is to develop an image-based model of urethral distention and resistance in women with and without SUI. METHODS: A biomechanical vector force model was created to simulate the mechanical deformation of pelvic floor structures during cough and Valsalva in order to measure urethral distension and predict flow resistance patterns. Dynamic MRI images were used to create a spatial model to construct an accurate representation of tissue thickness and location, which was combined with tissue property values (MATLAB 2011a, MathWorks, Natick, MA). Spatial profiles were created to demonstrate the effects of hypermobility and tissue property variability on distensibility and flow resistance along the urethra. Sensitivity analyses were conducted to demonstrate the relationship between flow resistance and various tissue properties. RESULTS: The average distension for incontinent cases (3.8 mm) was significantly greater than that of continent cases (2.6 mm) (t = 3.3083, df = 8, P < 0.01), corresponding to a 70% drop in average resistance to urine flow. Sensitivity analyses demonstrated that the stiffness and contractility of the vagina and urethra had the greatest effect on continence. CONCLUSIONS: We present a novel, 2-dimensional biomechanical model of female stress urinary incontinence (SUI) that relates the effects of various factors such as tissue elasticity, pelvic floor structure, and muscle activation. A better understanding of the pathophysiology underlying SUI has potential implications for the creation of novel targeted treatments.

Urodynamic characterization of lower urinary tract symptoms in women less than 40 years of age.

INTRODUCTION: Lower urinary tract symptoms (LUTS) in young women is becoming a more recognized urologic issue that can arise from many causes, each with their own management strategy. The purpose of this study was to determine the rates of various etiologies for LUTS in women under 40 years of age. MATERIALS AND METHODS: Video urodynamic studies (VUDS) were performed in 70 women age 40 years or less with LUTS for greater than 6 months between March 2005 and June 2012 at Weill Cornell Medical College. Patients with culture-proven bacterial urinary tract infections, pelvic organ prolapse greater than grade I, symptoms for less than 6 months, a history of neurologic disease, or previous urological surgery affecting voiding function, were excluded from the analysis. RESULTS: The mean age of the patients was 31.95 ± 5.57. There were 48 patients that presented with more than one urinary symptom (68.57%). The most frequent complaints included: urinary frequency (n = 42, 34.15%), incontinence (n = 26, 21.14%), and urinary urgency (n = 22, 17.89%). The most common urodynamic abnormality was dysfunctional voiding (n = 25, 28.74%), detrusor overactivity (n = 15, 20.00%), bladder outlet obstruction (n = 8, 11.43%). There were no significant differences seen in complaints or AUA symptom and quality of life scores across diagnosis groups. CONCLUSIONS: Persistent LUTS can present in younger women with an unclear etiology, which may be characterized using VUDS. The most common etiology found is dysfunctional voiding followed by detrusor overactivity. This study shows that the etiology can be more accurately determined using VUDs, which can assist in management.

Pathologic Outcomes following Urethral Diverticulectomy in Women.

Purpose. Although most urethral diverticula in women are benign, there is a subset of patients who develop malignant changes. Limited studies report the pathologic findings associated with this relatively rare entity. We describe the clinicopathologic findings of women who underwent urethral diverticulectomy. Methods. A consecutive series of 29 women who underwent surgical resection of a urethral diverticulum were identified between 1992 and 2013. Clinical and radiographic data was collected by retrospective review of patient medical records. All pathological slides were rereviewed by a single urologic pathologist. Results. Of the 14 women with clinical data, 9 (64%) presented with urgency, 7 (50%) with urinary frequency, 3 (21%) with urinary incontinence, and 3 (21%) with dysuria. Mean diverticular size was 2.3 (±1.4) cm. Although one patient (3%) had invasive adenocarcinoma on final pathology, the remaining 28 cases (97%) demonstrated benign features. The most common findings were inflammation (55%) and nephrogenic adenoma (21%). Conclusions. Although most urethral diverticula in women are benign, there is a subset of patients who develop malignancy in association with the diverticulum. In this series, 97% of cases had a benign histology. These findings are important when counseling patients regarding treatment options.

Identification of spermatogenesis in a rat sertoli-cell only model using Raman spectroscopy: a feasibility study.

PURPOSE: We determined whether Raman spectroscopy could identify spermatogenesis in a Sertoli-cell only rat model. MATERIALS AND METHODS: A partial Sertoli-cell only model was created using a testicular hypothermia-ischemia technique. Bilateral testis biopsy was performed in 4 rats. Raman spectra were acquired with a probe in 1 mm3 samples of testicular tissue. India ink was used to mark the site of spectral acquisition. Comparative histopathology was applied to verify whether Raman spectra were obtained from Sertoli-cell only tubules or seminiferous tubules with spermatogenesis. Principal component analysis and logistic regression were used to develop a mathematical model to evaluate the predictive accuracy of identifying tubules with spermatogenesis vs Sertoli-cell only tubules. RESULTS: Raman peak intensity changes were noted at 1,000 and 1,690 cm(-1) for tubules with spermatogenesis and Sertoli-cell only tubules, respectively. When principal components were used to predict whether seminferous tubules were Sertoli-cell only tubules or showed spermatogenesis, sensitivity and specificity were 96% and 100%, respectively. The ROC AUC to predict tubules with spermatogenesis with Raman spectroscopy was 0.98. CONCLUSIONS: Raman spectroscopy is capable of identifying seminiferous tubules with spermatogenesis in a Sertoli-cell only ex vivo rat model. Future ex vivo studies of human testicular tissue are necessary to confirm whether these findings can be translated to the clinical setting.

Clinical and investigative applications of Raman spectroscopy in Urology and Andrology.

Raman spectroscopy (RS) is an optical technique that allows for real-time interrogation of biologic tissues with chemical specificity. Using a diode laser, incident photons are scattered on the tissue of interest and the spectral wavelength output is a reflection of the tissues' molecular fingerprint. Naturally, this technology has come into clinical usage to evaluate benign versus malignant tissue. Within the field of Urology, RS has seen tremendous growth as an optical biopsy tool for the real-time evaluation of diseases of the bladder, prostate, kidney, and testis. With such growing fervor for this emerging spectroscopic modality, we present a current summary of clinical studies utilizing RS within Urology and Andrology to highlight its potential applications.

Microsurgical denervation of the rat spermatic cord and its connection to the diagnosis and treatment of chronic orchialgia: a bench to bedside experience.

Chronic orchialgia is a common urologic problem, however, determination of the etiology is often difficult and the pathophysiology is poorly understood. As a result, there is no clear algorithm for surgical treatment for men who have failed conservative medical treatment. This review aims to describe microsurgical denervation of the rat spermatic cord (SC) and summarize several surgical techniques that have been described in the literature ranging from orchiectomy to epididymectomy to vasectomy reversal for post-vasectomy orchialgia. More recent studies advocate for microsurgical denervation of the spermatic cord (MDSC), which can be performed with a standard operating microscope or laparoscopic/robotic techniques providing optical magnification. Data regarding efficacy and complications for all surgical treatments is outlined. Experimental modalities, such as the use of multiphoton microscopy (MPM) to identify and ablate nerves surrounding the vas deferens are also described. Finally, given the fact that chronic orchialgia often affects young men, we summarize safety data generated from an animal model regarding the effect of microsurgical denervation on the structure and function of the testis and vas deferens.

A cost-effectiveness analysis of retropubic midurethral sling versus transobturator midurethral sling for female stress urinary incontinence.

AIMS: To compare the cost-effectiveness (CE) of retropubic midurethral sling (RMS) versus transobturator midurethral sling (TMS) for the treatment of female stress urinary incontinence (SUI). METHODS: A Markov chain decision model was created to simulate treatment of SUI with RMS versus TMS. Costing data were obtained from the Medicare RBRVS. Data regarding the efficacy and complications associated with RMS versus TMS was compiled from a literature review of 21 randomized RCTs with a minimum of 12 months follow-up, as were corresponding utilities for different continence states. Deterministic and probabilistic estimates of cost-effectiveness (CE) for each procedure were calculated and compared, and sensitivity analyses were performed. RESULTS: In the base-case deterministic analysis, the efficacy of RMS was 6.275 versus 6.272 QALYs for TMS. QALYs represent a measure of disease burden accounting for both quantity and quality of life lived and are used to assess the monetary value of a medical intervention. The average cost for treatment with RMS however was higher at $9,579 versus $9,017 with TMS. TMS was therefore overall more cost-effective than RMS (CE = $1,438/QALY vs. $1,527/QALY). Sensitivity analysis demonstrated that physician and sling characteristics such as device cost, surgeon fee, efficacy of treatment, operative time, and duration of hospitalization could all affect the relative CE of the therapies. CONCLUSIONS: Our study demonstrated that TMS was more cost-effective than RMS as a treatment for female SUI. The efficacy of the two treatments could be affected by physician and sling characteristic factors.

Microsurgical denervation of rat spermatic cord: safety and efficacy data.

OBJECTIVE: To describe a microsurgical technique for denervation of the spermatic cord and use of multiphoton microscopy (MPM) laser to identify and ablate residual nerves after microsurgical denervation. To evaluate structural and functional changes in the rat testis and vas deferens after denervation. MATERIALS AND METHODS: Nine Sprague-Dawley rats were divided into three experimental groups: sham, microsurgical denervation of the spermatic cord (MDSC), and MDSC immediately followed by laser ablation with MPM. At 2 months after surgery, we assessed testicular volume, functional circulation of the testicular artery with Doppler, patency of the vas deferens, and histology of the testis and vas deferens. RESULTS: There was a significant decrease in the median number of nerves remaining around the vas deferens with MDSC alone (3.5 nerves) or MDSC with MPM (1.5 nerves) compared with sham rats (15.5 nerves) (P = 0.003). Although, MDSC with MPM resulted in the fewest remaining nerves, this result was similar to MDSC alone (P = 0.29). No deleterious effects on spermatogenesis or vas patency were seen in the experimental groups when compared with the sham rats. CONCLUSION: A microsurgical approach can be used to effectively and safely denervate the rat spermatic cord with minimal changes to structure and function of the testis and vas deferens. MPM can be used as an adjunct to identify and ablate residual nerves after MDSC.

Trends and inequalities in the surgical management of ureteric calculi in the USA.

OBJECTIVE: To assess trends in the surgical management of ureteric calculi over a 10-year period. MATERIALS AND METHODS: An analysis of the 5% Medicare Public Use Files, from 2001, 2004, 2007 and 2010, was performed to assess the use of ureteroscopy (URS), extracorporal shockwave lithotripsy (ESWL) and ureterolithotomy (UL) in treating ureteric calculi. Patients were identified using International Classification of Diseases 9th edition (Clinical Modification) and Current Procedure Terminology codes. Statistical analyses using the Fisher and chi-squared tests, and multivariate logistic regression analysis (dependent variables: URS, ESWL, UL, treatment, no treatment; independent variables: age, gender, ethnicity, geography and year of treatment) were performed. RESULTS: A total of 299 920 patients with ureteric calculi were identified. Of these, 115 200 underwent surgery. Men (odds ratio [OR] = 1.15, P < 0.001) were more likely, while patients from ethnic minorities (OR = 0.84, P = 0.004) were less likely to be treated. Patients in the West of the USA were also less likely to be treated (OR = 0.76, P < 0.001) as were patients aged <65 or >84 years old (P = 0.29). The predominant surgical approach was URS (65.2%), followed by ESWL (33.6%) and UL (1.2%). The use of URS increased over time, while the use of ESWL and UL declined. Women (OR = 1.25, P < 0.001) were more likely to undergo URS. Patients in the South of the USA (OR = 1.51, P < 0.001) and patients from ethnic minorities were more likely to undergo ESWL (OR = 1.23, P = 0.03). CONCLUSIONS: The surgical treatment of ureteric calculi changed significantly between 2001 and 2010. The use of URS expanded at the expense of ESWL and UL. Multiple inequalities existed in overall surgical treatment rates and in the choice of treatment; age, gender, ethnicity and geography influenced both whether patients underwent surgical intervention and the type of surgical approach used.

Cost-effectiveness analysis of tension-free vaginal tape vs burch colposuspension for female stress urinary incontinence in the USA.

OBJECTIVE: To compare the cost-effectiveness (CE) of tension-free vaginal tape (TVT) with that of burch colposuspension (BC) for the treatment of female stress urinary incontinence (SUI). MATERIALS AND METHODS: A Markov-chain decision model was created to simulate treatment of SUI with TVT or BC using Treeage Pro 2011 software (Treeage Software Inc., Williamstown, MA, USA). Costing data were obtained from the Medicare Resource-Based Relative Value Scale. Data regarding the success of TVT vs BC were obtained from the peer-reviewed literature, as were corresponding utilities for different continence states. The CE of each procedure was calculated and compared, and sensitivity analyses were performed. RESULTS: At 10-year follow-up, TVT was more cost-effective (CE = $1495/quality-adjusted life year [QALY]) than BC (CE = $1824/QALY). Sensitivity analysis showed that TVT was more cost-effective than BC if the cost of the TVT device was <$3220. If the probability of success after TVT was <42%, then BC became the more cost-effective strategy (CE = $1827/QALY). CONCLUSION: Our study showed that TVT was more cost-effective than BC as a treatment for female SUI. Both cost of TVT device and efficacy of the procedure affect the CE analysis.

Trends in the utilization of percutaneous and open nephrolithotomy in the treatment of renal calculi.

PURPOSE: To evaluate trends in the use of percutaneous nephrolithotomy (PCNL) and nephrolithotomy (NL) in patients with renal pelvis calculi. MATERIALS AND METHODS: An analysis of the 5% Medicare Public Use Files (years 2001, 2004, 2007, and 2010) was performed to assess changes in the use of PCNL and NL over a 10-year period. Patients were identified using the International Classification of Diseases-9 (cm) and Current Procedure Terminology codes. Statistical analyses, including the Fisher and chi-square tests and multivariate regression analyses, were performed using SAS 9.3 (SAS Institute Inc, Cary, NC) and SPSS v20 (IBM Corp., Armonk, NY). RESULTS: A total of 26,100 patients underwent either PCNL or NL. Use of PCNL and NL decreased from 3.1% to 2.5% in patients with a diagnosis of stones (P<0.0001). Women (odds ration [OR]=1.19, P=0.003) were more likely to undergo surgery. Patients aged ≥65 years were less likely to be treated (OR=0.65-0.71, P<0.05). Patients treated after 2004 were less likely to undergo surgery (OR=0.77-0.84, P<0.05). The use of PCNL exceeded NL at a stable 10:1 ratio. CONCLUSIONS: The use of PCNL and NL for treatment of patients with stone disease slightly decreased from 2001 to 2010, although the number of patients with renal calculi increased. The use of PCNL vs NL was unchanged during this period. Multiple inequalities existed in overall surgical treatment rates and were influenced by sociodemographic factors such as age and sex.

Use of the Bulbocavernosus Reflex System in assessing voiding dysfunction.

PURPOSE: The Bulbocavernosus Reflex System (BRS) (Laborie, Canada) is an office-based procedure used to measure the bulbocavernosus reflex (BCR) latency period. The aim of this study is to evaluate the BCR as a predictor of specific voiding dysfunction patterns confirmed by urodynamics (UDS). METHODS: A total of 87 men were evaluated with BRS, UDS, and electromyography at Weill Cornell Medical College from March to August 2010. Baseline characteristics, demographics, UDS, and latency parameters were recorded. Multivariate logistic regression analysis was performed to evaluate prolonged BCR (latency >45 ms) as a predictor of specific voiding dysfunction patterns. RESULTS: The median age of men was 70.4 years (IQR 57.6-75.6). Based on UDS, 60 men were given a primary or secondary diagnosis of bladder outlet obstruction (BOO), 43 a diagnosis of detrusor overactivity (DO), 11 a diagnosis of intrinsic sphincter deficiency (ISD), and 4 a diagnosis of detrusor sphincter dyssynergia (DSD). Median BCR latency was 57.0 ms (IQR 47.5-76.5) and 68 (78%) men demonstrated a prolonged latency. In multivariate analysis, latency period was not significantly associated with DO, BOO, ISD, or DSD (p = 0.067, 0.696, 0.999, 0.971, respectively). CONCLUSIONS: Prolonged bulbocavernosus reflex latency was not associated with DO, BOO, ISD, or DSD. Although evidence in the literature suggests a link between this reflex arc and voiding, its specific diagnostic role remains unclear. Large prospective trials are needed to further explore the role of BCR in the evaluation of patients with voiding dysfunction.

A phase I trial of intravesical nanoparticle albumin-bound paclitaxel in the treatment of bacillus Calmette-Guérin refractory nonmuscle invasive bladder cancer.

PURPOSE: Up to 50% of patients treated with intravesical agents for high grade nonmuscle invasive bladder cancer will have disease recurrence. Response rates to current second line intravesical therapies are low and for these high risk patients novel agents are necessary. Our previously completed phase I trial showed docetaxel was a safe agent for intravesical use. Nanoparticle albumin-bound paclitaxel (Abraxane®, ABI-007) has been shown to have increased solubility and lower toxicity compared to docetaxel in systemic therapy. Thus, we assessed the dose limiting toxicity and maximum deliverable dose of intravesical nanoparticle albumin-bound paclitaxel. MATERIALS AND METHODS: Inclusion criteria for this institutional review board approved phase I trial were recurrent high grade Ta, T1 and Tis transitional cell carcinoma of the bladder for which at least 1 prior standard intravesical regimen failed. Six weekly instillations of nanoparticle albumin-bound paclitaxel were administered with a modified Fibonacci dose escalation model used until the maximum deliverable dose was achieved. The primary end point was dose limiting toxicity and the secondary end point was response rate. RESULTS: A total of 18 patients were enrolled in the study. One patient demonstrated measurable systemic absorption after 1 infusion. Grade 1 local toxicities were experienced by 10 (56%) patients with dysuria being the most common, and no grade 2, 3 or 4 drug related local toxicities were encountered. Of the 18 patients 5 (28%) had no evidence of disease at posttreatment evaluation. CONCLUSIONS: Intravesical nanoparticle albumin-bound paclitaxel exhibited minimal toxicity and systemic absorption in the first human intravesical phase I trial to our knowledge. A larger phase II study has begun to formally evaluate the activity of this regimen.

Long-term clinical outcomes of a phase I trial of intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to standard intravesical therapy.

OBJECTIVES: To report the long-term clinical outcomes and durability of response after treatment with induction intravesical docetaxel. Most novel agents used to treat bacillus Calmette-Guerin refractory high-grade non-muscle-invasive (NMI) bladder cancer are evaluated only after short follow-up periods. Our previously published phase I trial demonstrated that docetaxel is a safe agent for intravesical therapy with minimal toxicity and no detectable systemic absorption. We sought to determine long-term clinical outcomes after treatment with intravesical docetaxel. METHODS: Eighteen patients with recurrent Ta (n = 7), T1 (n = 5), and Tis (n = 6) transitional cell carcinoma who experienced treatment failure with at least 1 prior intravesical therapy completed the phase I trial. Docetaxel was administered as 6 weekly intravesical instillations using a dose-escalation model terminated at 0.75 mg/mL. Efficacy was evaluated by interval cystoscopy with biopsies when indicated, cytology, and computed tomography imaging. Follow-up consisted of quarterly cystoscopy, cytology, computed tomography, and biopsy when indicated. RESULTS: With a median follow-up of 48.3 months, 4 patients (22%) have demonstrated a complete durable response and currently remain disease-free without further treatment. Three patients (17%) had a partial response, defined as a single NMI recurrence with no further therapy for bladder cancer. Eleven patients (61%) failed treatment, and required another intervention. One patient developed stage progression. No delayed toxicities were noted. The median disease-free survival time was 13.3 months. CONCLUSIONS: After 4 years of follow-up without maintenance therapy, intravesical docetaxel has demonstrated the ability to prevent recurrence in a select number of patients with refractory NMI bladder cancer and warrants further investigation.

Significant change in predicted risk of biochemical recurrence after radical prostatectomy more common in black than in white men.

OBJECTIVES: To examine by race how frequently the data after radical prostatectomy translates into a substantial change in prognosis. Many nomograms exist to predict the survival outcomes using the pretreatment clinical parameters and post-treatment pathologic parameters. Race might be an important factor affecting their predictive ability. METHODS: Kattan nomograms were used to calculate the pretreatment and post-radical prostatectomy 5-year progression-free probability for each patient. The difference between the nomogram scores was used to divide the patients into 3 groups. A decrease in probability of >or=15 percentage points was classified as a significant increase in the probability of recurrence, an increase of >or=15 points was classified as a significant decrease in the probability of recurrence, and an absolute change of <15 points was considered no significant change. RESULTS: The data from 1709 (132 black and 1577 white) men were analyzed. Among the black men, 26.5% had an increase in the probability of recurrence, 57.6% had no change, and 15.9% had a decrease in the probability of recurrence. Among the white men, 13.8% had an increase in the probability of recurrence, 64.5% had no change, and 21.7% had a decrease in the probability of recurrence. Black men were twice as likely to have a significant increase in the probability of recurrence postoperatively compared with white men after adjusting for preoperative prostate-specific antigen level, clinical stage, and biopsy Gleason sum (odds ratio 2.0, 95% confidence interval 1.3-3.1, P = .002). CONCLUSIONS: These data could assist clinicians when counseling black men regarding their treatment options according to their preoperative risk profile.