Effectiveness of convective water vapor energy therapy versus prostatic urethral lift for symptomatic benign prostatic hyperplasia: a systematic review and indirect comparison.

PURPOSE: To synthesize the evidence from randomized controlled trials of prostatic urethral lift (PUL) and convective water vapor thermal energy therapy (WAVE) for minimally invasive treatment of men with benign prostatic hyperplasia. METHODS: A systematic search of databases was performed to identify trials comparing WAVE or PUL to either an active or sham surgery control in subjects with symptomatic benign prostatic obstruction. A controlled indirect treatment comparison based on the approach of Bucher was performed for outcomes including International Prostate Symptom Score and maximum urinary flow rate (Qmax). The durability of treatment response was assessed by life-table analysis of freedom from retreatment through 4 years. RESULTS: Two multicenter sham-controlled trials (Rezum II Study, NCT01912339: LIFT Study, NCT01294150) were identified. The trials employed a common sham procedure and were similar with respect to their designs and subjects' baseline characteristics. Comparisons on the treatment effect in excess of sham response found non-significant differences between WAVE and PUL for symptom score [mean difference (MD): - 1.7 points; 95% confidence interval (CI): - 4.8, 1.4] but Qmax improvements favored WAVE [MD: 3.4 ml/sec; CI: 1.2, 5.6]. The proportion free of retreatment through 4 years was 89.1% for WAVE versus 75.4% for PUL [log-rank P = 0.004]. CONCLUSIONS: PUL and WAVE provide similar subjective improvements but flow-rate improvement and durability of response seem greater for WAVE. The confirmation of these findings in a randomized trial is warranted.

Functional Recovery, Oncologic Outcomes and Postoperative Complications after Robot-Assisted Radical Prostatectomy: An Evidence-Based Analysis Comparing the Retzius Sparing and Standard Approaches.

PURPOSE: We report a 1-year update of functional urinary and sexual recovery, oncologic outcomes and postoperative complications in patients who completed a randomized controlled trial comparing posterior (Retzius sparing) with anterior robot-assisted radical prostatectomy. MATERIALS AND METHODS: A total of 120 patients with clinically low-intermediate risk prostate cancer were randomized to undergo robot-assisted radical prostatectomy via the posterior and anterior approach in 60 each. Surgery was performed by a single surgical team at an academic institution. An independent third party ascertained urinary and sexual function outcomes preoperatively, and 3, 6 and 12 months after surgery. Oncologic outcomes consisted of positive surgical margins and biochemical recurrence-free survival. Biochemical recurrence was defined as 2 postoperative prostate specific antigen values of 0.2 ng/ml or greater. RESULTS: Median age of the cohort was 61 years and median followup was 12 months. At 12 months in the anterior vs posterior prostatectomy groups there were no statistically significant differences in the urinary continence rate (0 to 1 security pad per day in 93.3% vs 98.3%, p = 0.09), 24-hour pad weight (median 12 vs 7.5 gm, p = 0.3), erection sufficient for intercourse (69.2% vs 86.5%) or postoperative Sexual Health Inventory for Men score 17 or greater (44.6% vs 44.1%). In the posterior vs anterior prostatectomy groups a nonfocal positive surgical margin was found in 11.7% vs 8.3%, biochemical recurrence-free survival probability was 0.84 vs 0.93 and postoperative complications developed in 18.3% vs 11.7%. CONCLUSIONS: Among patients with clinically low-intermediate risk prostate cancer randomized to anterior (Menon) or posterior (Bocciardi) approach robot-assisted radical prostatectomy the differences in urinary continence seen at 3 months were muted at the 12-month followup. Sexual function recovery, postoperative complication and biochemical recurrence rates were comparable 1 year postoperatively.

Efficient delivery of radical cystectomy after neoadjuvant chemotherapy for muscle-invasive bladder cancer: a multidisciplinary approach.

BACKGROUND: Cystectomy delay >90 days after a diagnosis of muscle-invasive bladder cancer (MIBC) adversely affects pathologic stage and survival outcomes in patients who undergo primary surgery. After neoadjuvant chemotherapy (NAC), the impact of the timing of cystectomy delivery on these outcomes is uncertain. Poor communication between urologic and medical oncologists can result in cystectomy delay after systemic treatment. The authors of this report hypothesized that a delay in cystectomy delivery after NAC is associated with adverse survival outcomes. METHODS: An eligible cohort of 153 patients with MIBC received NAC and underwent radical cystectomy between 1990 and 2007. At the authors' institution, the genitourinary team strives to schedule patients for surgery at the time of initial evaluation or after their first chemotherapy cycle. Clinicopathologic characteristics, including timing of cystectomy, chemotherapy delivery, vital status, and reasons for excessive surgical delay, were analyzed retrospectively using an institutional database. A Cox proportional regression model was used to test the association between the timing of cystectomy delivery and survival. RESULTS: The median follow-up for all patients was 3.6 years. The median time to cystectomy was 16.6 weeks and 6.9 weeks from the first and last day of NAC, respectively. In multivariate analyses, the timing of cystectomy delivery from the termination of NAC did not significantly alter the risk of survival. The most common reason for cystectomy delivery beyond 10 weeks (28 patients; 18%) was procedural scheduling. CONCLUSIONS: Cystectomy delivery within 10 weeks after NAC did not compromise patient survival and, thus, provided a reasonable window for patient recovery and surgical intervention.

Loss of 15-hydroxyprostaglandin dehydrogenase expression contributes to bladder cancer progression.

Prostaglandin E2, which is known to contribute to cancer progression, is inactivated by the catabolic enzyme, 15-hydroxyprostaglandin dehydrogenase (PGDH), which has tumor-suppressor activity in lung, colon, breast, and gastric cancers. Therefore, we evaluated the expression of PGDH in human bladder cancer tissue specimens and cell lines. Immunoperoxidase staining of bladder cancer tissues demonstrated that (1) PGDH is highly expressed by normal urothelial cells but (2) reduced in many low stage (Ta/Tis) bladder cancers, and (3) PGDH is completely lost in most invasive bladder cancers. Of eight cancer cell lines tested, only two relatively well-differentiated bladder cancer cell lines, RT4 and UM-UC9, expressed PGDH. Moreover, inhibition of PGDH expression in well-differentiated RT4 cells using small inhibitory RNA or short hairpin RNA resulted in a more aggressive phenotype with increased motility and anchorage-independent growth. Additionally, PGDH knockdown affected prostaglandin E2 signaling as measured by cAMP generation. These data indicate that loss of PGDH expression contributes to a more malignant bladder cancer phenotype and may be necessary for bladder cancer development and/or progression.

Long-term outcomes of intravesical therapy for non-muscle invasive bladder cancer.

OBJECTIVES: The purpose of the current review was to evaluate the long-term outcomes of intravesical therapy for non-muscle invasive bladder cancer. METHODS: A literature search was performed to identify studies documenting long-term outcomes of intravesical therapy for non-muscle invasive bladder cancer. Data from each study were collected using standardized forms that included information on author, date of study, journal, study type, intravesical therapy used, number of patients, length of follow-up, and outcome measures (recurrence, progression, and disease-specific and overall mortality). This information was then tabulated and summarized. RESULTS: Of 420 publications identified, 79 were chosen for data abstraction. The long-term impact of intravesical BCG, mitomycin, epirubicin (with or without maintenance/with or without immediate therapy), and transurethral resection alone demonstrated marginal impact on recurrence. However, BCG with or without maintenance appeared to reduce disease progression over the long term compared to other therapies. Data on mortality associated with intravesical therapy were limited. In general, the literature was limited by inconsistent reporting of outcomes and lack of standardization. CONCLUSIONS: Long-term outcomes after intravesical therapy for non-muscle invasive bladder cancer are difficult to asses due to the lack of quality long-term data and inconsistencies in reporting results. It is clear that better long-term data are needed to define the impact of intravesical therapy on the natural history of the disease.

Low Interrater Reliability of Videourodynamic Diagnosis of Detrusor External Sphincter Dyssynergia.

OBJECTIVES: Complex bladder dysfunction requires urodynamic testing, often under fluoroscopy termed videourodynamic study (VUDS), to assist the diagnosis and management. Videourodynamic study is an objective tool with high interrater reliability (IRR) for identifying detrusor overactivity. However, IRR has not been validated with disorders associated with neurogenic bladder (NGB). We aim to investigate the IRR of VUDS to diagnose detrusor external sphincter dyssynergia (DESD) among NGB patients and hypothesize a high IRR to DESD diagnosis on VUDS. METHODS: Videourodynamics tracings with fluoroscopic images were rated either positive or negative for evidence of DESD by 4 raters (2 neurourologists, neurourology fellow, and urology postgraduate year 2 resident), in patients who underwent VUDS from 2013 to 2017. The study population had known NGB without previous bladder reconstruction. The IRR was determined using percent agreement and κ values. RESULTS: The experts had a percent agreement of 82.1% (κ = 0.26). Expert 1 and expert 2 had a percent agreement of 63.6% (κ = 0.1497) and 68.9% (κ = 0.2967), respectively, when compared with the fellow. Sensitivity and specificity ranged from 28% to 75% and 64% to 93%, respectively. The negative predictive values ranged from 90% to 95%. CONCLUSIONS: The IRR to diagnose DESD on VUDS was much lower than expected, even among experts, and was likely multifactorial and partially owing to lack of clinical context and lack of standardized VUDS interpretation of the electromyogram. A high negative predictive value was found among all participants. Further research is needed to evaluate factors contributing to the low reproducibility of DESD diagnosis on VUDS.

Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy: A Meta-analysis of Oncologic, Perioperative, and Complication-related outcomes.

Robot-assisted radical cystectomy (RARC) is increasingly being used to treat muscle-invasive bladder cancer in an attempt to improve functional outcomes and complication rates over open radical cystectomy (ORC). We performed a meta-analysis of randomized controlled trials (RCTs) to compare patient outcomes between RARC and ORC. The primary outcome measure was a composite of recurrence-free survival (RFS) or progression-free survival (PFS). As a secondary measure, we examined other surrogate oncologic endpoints, perioperative outcomes, and complications. We found no difference between RARC and ORC with respect to RFS/PFS (hazard ratio 0.89, 95% confidence interval 0.64-1.24), surgical margin rates, or lymph node dissection yield. Analysis of patterns of recurrence for (pelvic) versus distant/abdominal sites indicated a significant difference between RARC and ORC (p=0.04). This analysis represents a combination of post hoc analyses using RCT data and inconsistent between-study definitions of recurrence sites, and must be interpreted with caution. Lastly, RARC was associated with an advantage in estimated blood loss, but a longer operative time, with no difference in hospital length of stay or complication rates. These data support the oncologic safety of RARC; however, further research is required to assess potential differences in recurrence patterns. PATIENT SUMMARY: We synthesized data from recent randomized controlled trials to examine differences in cancer control between minimally invasive, robot-assisted radical cystectomy and traditional, open radical cystectomy. Our study shows that cancer control outcomes are comparable between robotic and open techniques, supporting the safety of minimally invasive surgery. Blood loss was lower in robotic surgery, but the robotic procedure was longer and did not have lower complications rates after surgery.

Aquablation outcomes for the U.S. cohort of men with LUTS due to BPH in large prostates (80-150 cc).

Between September and December 2017, 82 men with moderate-to-severe lower urinary tract symptoms due to benign prostatic hyperplasia LUTS/BPH and prostate volume of 80-150 cc underwent Aquablation in a prospective multicenter clinical trial in the United States. Baseline patient and clinical demographics and standardized postoperative parameters were collected and tabulated in a central independently monitored database. Adverse events through 3 months were adjudicated by an independent clinical events committee. Mean pre-treatment prostate volume was 108 ± 21.1 cc. Mean operative time was 38.2 ± 14.4 min and mean Aquablation resection time was 7.7 ± 3.3 min. Additional electrocautery for hemostasis was not needed in any patient following Aquablation. The average length of stay following the procedure was 1.6 ± 1.0 days. Mean pre- and 3 months post-treatment IPSS scores were 23.7 ± 6.4 and 7.1 ± 5.1, -16.6, p < 0.01. Mean pre- and 3 months post-treatment Qmax were 9.2 ± 3.3 ml/s and 19.5 ± 13 ml/s, + 10.8 ml/s, p < 0.01. Mean pre- and 3 months post-treatment post-void residuals were 120.6 ± 119.1 cc and 50.6 ± 61.6 cc, -72.0 cc, p < 0.01. The observed Clavien-Dindo grade 2 or higher event rate at 3 months was 34.1%. Aquablation is a safe and effective treatment option for men with large prostates (80-150 cc) suffering from LUTS/BPH.

Overactive bladder: recognition requires vigilance for symptoms.

Overactive bladder (OAB) is a prevalent condition in both men and women that imposes significant burdens on the patient and his or her quality of life. Nevertheless, only a small percentage of patients with OAB receive diagnosis and treatment. The identification of OAB is well within the scope of the primary care provider, as it is symptom-based and does not generally require specialized testing. The treatment of OAB relies on behavioral modification and/or pharmacologic options, primarily antimuscarinic therapy. Better identification of OAB symptoms in the primary care setting should reduce the number of patients suffering from untreated OAB.

Complications associated with single-dose, perioperative mitomycin-C for patients undergoing bladder tumor resection.

OBJECTIVES: To better understand the risk of short-term complications associated with perioperative intravesical mitomycin-C (MMC) therapy for patients undergoing endoscopic management of non-muscle invasive bladder cancer. METHODS AND MATERIALS: Using an institutional database of patients with bladder cancer, we performed a retrospective case-control study of patients receiving perioperative MMC after tumor resection (2008-2012). MMC cases were matched by clinical stage to controls receiving endoscopic resection alone. Demographic information, clinicopathologic details, and outcomes were compared between groups. Outcomes of interest included overall, genitourinary, and major complications. Chi-square tests and multivariable logistic regression were used to evaluate associations among patient characteristics, clinical factors, exposure to MMC, and outcomes of interest. RESULTS: One-hundred sixteen patients treated with MMC were matched to 116 controls. Patients receiving MMC were younger (P = 0.04) and more likely to have invasive disease (i.e. T1 or greater) (23% vs. 15%, P = 0.02). Complications were more frequent among patients who were treated with MMC (34.5% vs. 19.8%, Odds Ratio 2.89, 95% Confidence Interval 1.43-5.81). The most common complication among MMC patients that required medical management was dysuria (17%). Major complications were more common among MMC patients (5.2% vs. 0.9%), but this difference did not reach statistical significance (P = 0.11). CONCLUSIONS: Use of MMC is associated with a greater odds of complications compared with controls. Patients should be counseled regarding both the benefits and potential risks of perioperative intravesical MMC. Continued research is required to understand the safety implications associated with the use of perioperative, intravesical MMC.

Health-related quality of life outcomes after robot-assisted and open radical cystectomy using a validated bladder-specific instrument: a multi-institutional study.

OBJECTIVE: To evaluate health-related quality of life (HRQL) using validated bladder-specific Bladder Cancer Index (BCI) and European Organization for Research and Treatment of Cancer Body Image scale (BIS) between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC). METHODS: This was a retrospective case series of all patients who underwent radical cystectomy. Patients were grouped based on surgical approach (open vs robot assisted) and diversion technique (extracorporeal vs intracorporeal). Patients completed BCI and BIS preoperatively and at standardized postoperative intervals (at least 2). The primary exposure variable was surgical approach. The primary outcome measure was difference in interval and baseline BCI and BIS scores in each group. The Fisher exact, Wilcoxon rank-sum, and Kruskal-Wallis tests were used for comparisons. RESULTS: Eighty-two and 100 patients underwent RARC and ORC, respectively. Compared with RARC, more patients undergoing ORC had an American Society of Anesthesiology score≥3 (66% vs 45.1% RARC; P=.007) and shorter median operative time (350 vs 380 minutes; P=.009). Baseline urinary, bowel, sexual function, and body image were not different between both the groups (P=1.0). Longitudinal postoperative analysis revealed better sexual function in ORC group (P=.047), with no significant differences between both the groups in the other 3 domains (P=.11, .58, and .93). Comparisons regarding diversion techniques showed similar findings in baseline and postoperative HRQL data, with no significant differences in the HRQL and body image domains. CONCLUSION: RARC has comparable HRQL outcomes to ORC using validated BCI and BIS. The diversion technique used does not seem to affect patients' quality of life.

Matched comparison of robotic-assisted and open radical cystectomy.

OBJECTIVE: To evaluate our initial robotic-assisted radical cystectomy (RARC) experience compared with a robust open radical cystectomy (ORC) series performed at a single institution using a matched-pair analysis. Although early results suggest that RARC is safe, with favorable perioperative and early oncologic outcomes, limited data exist comparing ORC and RARC. METHODS: RARC and ORC patients were identified through a prospectively maintained institutional review board-approved bladder cancer database. RARC and ORC cases performed from September 2007 to November 2010 were matched 1:2 by age, sex, urinary diversion, and clinical stage. The perioperative, complication, and pathologic outcomes were compared. RESULTS: A total of 50 RARC and 100 ORC cases were reviewed, with a median follow-up of 8 and 13.5 months, respectively. No differences in the demographic parameters were present between the 2 groups. RARC was associated with a significantly decreased median estimated blood loss (350 vs 475 mL) and 30-day transfusion rate (2% vs 24%) but with longer operative times (454.9 vs 349.1 minutes). No difference was found in the rate of 30-day minor or major Clavien complications, length of stay, or 30-day readmissions between groups. The 90-day mortality rate was 3% versus 0% for ORC and RARC, respectively. No difference in the final pathologic findings, number of lymph nodes removed, or margin status was identified. CONCLUSION: Early experience with RARC compared with a robust ORC experience demonstrated similar perioperative and pathologic outcomes. Continued experience with RARC has the potential to bring improved perioperative results.

Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression.

Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.