Early PSA decline after starting second-generation hormone therapy in the post-docetaxel setting predicts cancer-specific survival in metastatic castrate-resistant prostate cancer.

BACKGROUND: The objective of this study was to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in patients with taxane-refractory metastatic castrate-resistant prostate cancer (mCRPC) and evaluate utility of this metric in informing intensified surveillance/imaging protocols. METHODS: We retrospectively identified 75 mCRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized patients into two cohorts based on the first PSA within 3 months after initiation of therapy: PSA reduction ≥50% (Group A) and PSA reduction <50% (Group B). The primary endpoint was cancer-specific mortality (CSM). The secondary endpoint was radiographic disease progression (rDP) on 2nd HT. In univariate and multivariate analyses, we investigated factors associated with rPD and CSM. RESULTS: We included 75 patients (52 in Group A, 23 in Group B) in the analytic cohort. Baseline clinico-demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. Median follow up time was 30 months and the median time to radiographic disease progression was 28.1 and 12.5 months (p = 0.002) in cohorts A and B, respectively. On univariate and multivariate analyses, both PSA reduction ≥50% and volume of metastatic disease were significantly associated with a decreased risk of radiographic disease progression (HR 0.41, 95% CI 0.21-0.80, p = 0.0113) as well as a decreased risk of cancer-specific mortality (HR 0.29, 95% CI 0.09-0.87, p = 0.0325). CONCLUSION: PSA reduction ≥50% within 3 months of starting 2nd HT was associated with significantly improved radiographic disease progression-free survival and 3-year cancer-specific mortality. This suggests using PSA 50%-decline metric in surveillance patients with on 2nd HT and identifies patients who require further evaluation with imaging.

Partial versus radical nephrectomy in clinical T2 renal masses.

OBJECTIVE: To report perioperative, renal functional and oncologic outcomes for patients undergoing partial or radical nephrectomy for cT2 renal masses. METHODS: Retrospective review of patients who underwent partial (n = 72) or radical nephrectomy (n = 379) for cT2 renal masses from 2000 to 2016. After propensity adjustment using inverse probability weighting, the following were compared by surgery (partial or radical nephrectomy): complications, renal function measured by estimated glomerular filtration rate as continuous and as <60 mL/min/1.73 m2 at 1 and 3 years postoperatively and overall, metastases-free survival and cancer-specific survival in patients with renal cell carcinoma. RESULTS: After propensity adjustment, clinical and radiographic features were well-balanced between groups. Overall and severe complications were more common for partial compared with radical nephrectomy, although not statistically significant (19 vs 13%, P = 0.14 and 4 vs 2%, P = 0.3, respectively). Estimated glomerular filtration rate change at 1 and 3 years was more pronounced in radical compared with partial nephrectomy (median -16 vs -5 and -14 vs -2, respectively, P < 0.001). A greater proportion of radical nephrectomy patients had an estimated glomerular filtration rate <60 at 1 and 3 years (55 vs 17% and 48 vs 17%, respectively, P < 0.01). In renal cell carcinoma patients, overall, metastases-free and cancer-specific survival were not significantly different between groups (median survivor follow up 7.1 years, interquartile range 3.6-11.4). CONCLUSIONS: Partial nephrectomy appears to be a relatively safe and a potentially effective treatment for cT2 renal masses, conferring better renal functional preservation compared with radical nephrectomy. These data support continued use of partial nephrectomy for renal masses >7 cm in appropriately selected patients.

Patient Attitudes Towards Surgical Management of Peyronie's Disease Prior to Men's Health Consultation.

OBJECTIVE: To evaluate clinical characteristics associated with patient attitudes toward surgical treatment of Peyronie's disease (PD) prior to consultation in a high-volume male sexual health clinic. METHODS: From 2014-2018 a prospective database was created of patients presenting to the sexual health clinic at our institution. Multivariable regression analysis was conducted to determine factors associated with pre-visit consideration of surgery. RESULTS: Of 1359 men presenting to clinic, 342 had a chief complaint of PD. Prior to consultation, 79% of patients (n = 270) stated they were willing to consider surgery to correct their PD symptoms. Factors associated with consideration of surgery included younger patient age (mean 55.8 vs 60.0 years; P = .008), history of depression/anxiety (21% vs 8%, P = .01), greater penile curvature (43.3 vs 34.6 degrees; P = .002), penile shortening (64% vs 44%; P = .003), pain with erections (46% vs 33%; P = .05) and decreased ability to have penetrative intercourse (51.9% vs 65.3%, P = .04). On multivariable analysis, age, history of depression, penile shortening, and mean curvature remained significantly associated. Symptom duration and relationship factors were not associated with a difference in the stated preference to consider surgery prior to consultation (P >.05 for all). CONCLUSION: Nearly 4 out of 5 patients reported willingness to consider surgical intervention for their PD-related symptoms prior to urologic consultation. On multivariable analysis, younger age, history of depression/anxiety, penile shortening, and curvature were associated with a greater likelihood of considering surgery. This information provides important insight into patient attitude toward undergoing surgery and will help drive patient counseling for men with PD.

Predictors of Patient Willingness to Consider Surgery Prior to Consultation at Sexual Health Clinic.

OBJECTIVE: To identify factors associated with patient willingness to consider surgical treatment for erectile dysfunction (ED) prior to urologic consultation. METHODS: A prospective database of patients presenting to the sexual health clinic at our institution was created from 2014 to 2018, consisting of previsit patient questionnaires and clinical information. Univariable and multivariable logistic regression analysis was performed to determine factors associated with consideration of surgery and decision to undergo surgery. RESULTS: Of 1359 men presenting to the clinic, 991 men had a chief complaint of ED with 630 (63.6%) considering surgery. On multivariable analysis, factors significantly associated with previsit willingness for surgery included history of diabetes mellitus (P = .0009), increasing symptom bother (P <.0001), and decreasing relationship duration (P = .0005). Approximately 16% (162/991) patients considering surgery prior to consultation ultimately underwent penile implant insertion. Multivariable analysis demonstrated that older age (P = .003), history of diabetes mellitus (P = .03), lower international index of erectile function-EF domain (P = .0009) and history of intracavernosal injection therapy (P <.0001) were significantly associated with proceeding to ED surgery. Initial declaration of willingness to undergo ED surgery led to nearly 8-fold increased odds for surgery (P <.0001). CONCLUSION: Over 60% of patients presenting for ED consultation considered surgical intervention, of whom 25% underwent penile prosthesis. Both patient and relationship factors were predictors of surgical willingness. Previsit surgical willingness was associated with highest odds of eventual decision for surgery, suggesting that knowledge of ED treatment options in the general public may play a role. Our findings highlight opportunities for shared decision-making in a patient-centered model of care.

Diet and Exercise Are not Associated with Skeletal Muscle Mass and Sarcopenia in Patients with Bladder Cancer.

BACKGROUND: There is limited understanding about why sarcopenia is happening in bladder cancer, and which modifiable and nonmodifiable patient-level factors affect its occurrence. OBJECTIVE: The objective is to determine the extent to which nonmodifiable risk factors, modifiable lifestyle risk factors, or cancer-related factors are determining body composition changes and sarcopenia in bladder cancer survivors. DESIGN, SETTING, AND PARTICIPANTS: Patients above 18 yr of age with a histologically confirmed diagnosis of bladder cancer and a history of receiving care at Duke University Medical Center between January 1, 1996 and June 30, 2017 were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bladder cancer survivors from our institution were assessed for their dietary intake patterns utilizing the Diet History Questionnaire II (DHQ-II) and physical activity utilizing the International Physical Activity Questionnaire long form (IPAQ-L) tools. Healthy Eating Index 2010 (HEI2010) scores were calculated from DHQ-II results. Body composition was evaluated using Slice-O-Matic computed tomography scan image analysis at L3 level and the skeletal muscle index (SMI) calculated by three independent raters. RESULTS AND LIMITATIONS: A total of 285 patients were evaluated in the study, and the intraclass correlation for smooth muscle area was 0.97 (95% confidence interval: 0.94-0.98) between raters. The proportions of patients who met the definition of sarcopenia were 72% for men and 55% of women. Univariate linear regression analysis demonstrated that older age, male gender, and black race were highly significant predictors of SMI, whereas tumor stage and grade, chemotherapy, and surgical procedures were not predictors of SMI. Multivariate linear regression analysis demonstrated that modifiable lifestyle factors, including total physical activity (p=0.830), strenuousness (high, moderate, and low) of physical activity (p=0.874), individual nutritional components (daily calories, p=0.739; fat, p=0.259; carbohydrates, p=0.983; and protein, p=0.341), and HEI2010 diet quality (p=0.822) were not associated with SMI. CONCLUSIONS: Lifestyle factors including diet quality and physical activity are not associated with SMI and therefore appear to have limited impact on sarcopenia. Sarcopenia may largely be affected by nonmodifiable risk factors. PATIENT SUMMARY: In this report, we aim to determine whether lifestyle factors such as diet and physical activity were the primary drivers of body composition changes and sarcopenia in bladder cancer survivors. We found that lifestyle factors including dietary habits, individual nutritional components, and physical activity do not demonstrate an association with skeletal muscle mass, and therefore may have limited impact on sarcopenia.

Comparative Postoperative Outcomes of Rezum Prostate Ablation in Patients with Large Versus Small Glands.

Introduction: Rezum water vapor thermal ablation is a new minimally invasive technique used to treat benign prostatic hyperplasia. Major advantages include minimal anesthesia and recovery time, low rate of sexual side effects, and durable clinical improvement. However, data are lacking regarding use of Rezum in prostate glands >80 cc. Here we seek to examine the clinical outcomes of men with large prostate glands following Rezum. Patients and Methods: We retrospectively reviewed patients who underwent Rezum therapy at our institution since July 2017. Three-month postoperative outcomes were analyzed, including American Urological Association symptom score (AUASS), peak flow, and postvoid residual (PVR). Complications, including hematuria and urinary tract infections, were also assessed. All statistical analyses were conducted using RStudio 1.2.1335. Results: One hundred eighty-two patients undergoing Rezum were identified, of whom 25.8% had prostate volume >80 cc. Mean gland volume in this group was 119 cc and 55.3% were catheter dependent. Following Rezum, statistically significant improvement was seen in AUASS from 22 to 13.4 (p = 0.04) and PVR from 305 to 149 cc (0.05). Statistically significant improvement was seen in peak flow rate from 7.7 to 12.7 mL/second (p = 0.002). In a subset of catheter-dependent patients, the postoperative catheter-free rate was 83% for men with glands >80 cc, which was comparable with 88% in the smaller gland group. Postoperative complication rate was not significantly different between large or small glands. Conclusions: In our experience, Rezum is efficacious in patients with glands >80 cc. Patients experience symptomatic and objective improvement in voiding parameters that is comparable with patients with glands smaller than 80 cc. Among catheter-dependent patients with glands >80 cc, over 80% are catheter free after Rezum. Our experience supports the consideration of Rezum in patients with prostate glands >80 cc; further studies are warranted to confirm long-term outcomes.

Use of Nitrous Oxide in Office-based Urologic Procedures: A Review.

Nitrous oxide (N2O) is underutilized in ambulatory urology. Here, we review available data regarding application, efficacy, and side effect profile of N2O in ambulatory urologic procedures. Data were available from 11 studies. N2O has been described in the setting of transrectal ultrasound-guided prostate biopsies, flexible cystoscopy, ureteral stent placement, and extracorporeal shockwave lithotripsy in adult patients and catheterization in children. Studies showed significant improvements in peri-procedural pain and anxiety relative to alternative (or none) forms of analgesia. Adverse effects were rare and self-limited. More widespread use of N2O may result in cost savings and better patient tolerance with outpatient procedures.

Prevalence and Predictors of Climacturia and Associated Patient/Partner Bother in Patients With History of Definitive Therapy for Prostate Cancer.

BACKGROUND: Climacturia is an under-reported complication of definitive therapy for prostate cancer (PCa) - that is, radical prostatectomy (RP) and/or radiation therapy (RT). AIM: We sought to identify the prevalence and predictors of climacturia and associated patient/partner bother in patients with and without prior PCa treatment. METHODS: We analyzed a database of patients who presented to our Men's Health clinic and filled out a questionnaire related to sexual function and pertinent medical histories. The prevalence of climacturia and associated patient/partner bother in patients with/without prior RP/RT was calculated. Univariable and multivariable logistic regressions were performed to identify predictors associated with climacturia and patient/partner bother. OUTCOMES: The primary outcomes were the prevalence and predictors of climacturia and associated patient/partner bother in patients with/without history of definitive PCa treatment. RESULTS: Among 1,117 patients able to achieve orgasm, 192 patients (17%) had prior history of definitive therapy for PCa (RP alone = 139 [72%]; RT alone = 22 [11%]; RP + RT = 31 [16%]). Climacturia was reported by 39%, 14%, 52%, and 2.4% of patients with history of RP alone, RT alone, RP + RT, and neither RP nor RT, respectively (P < .05 between all groups). 33 to 45 percent of patients with climacturia noted significant patient/partner bother. Factors significantly associated with climacturia were prior RP, prior RT, history of other prostate surgery, and erectile dysfunction, although erectile dysfunction was not significant on multivariable analysis. Significant reduction in climacturia prevalence was noted for patients who were ≥1 year out from RP, compared with patients who were <1 year out. Among patients with prior RP/RT, stress urinary incontinence was associated with increased risk of climacturia, whereas diabetes was associated with decreased risk. No factors were associated with patient/partner bother. Among patients with prior RP, nerve-sparing technique did not predict presence of climacturia but was associated with reduced patient/partner bother. CLINICAL TRANSLATION: Given significant prevalence of climacturia and associated patient/partner bother, patients should be counseled on the risk of climacturia before undergoing RP/RT. STRENGTHS AND LIMITATIONS: Strengths include the large study population and the focus on both RP and RT. Limitations include the facts that this is a single-institution study that primarily relies on patients' subjective reporting and that the study population may not represent the general population. CONCLUSIONS: Climacturia affects a significant proportion of patients with history of RP/RT for PCa, and many patients and their partners find this bothersome. Jimbo M, Alom M, Pfeifer ZD, et al. Prevalence and Predictors of Climacturia and Associated Patient/Partner Bother in Patients With History of Definitive Therapy for Prostate Cancer. J Sex Med 2020;17:1126-1132.

Dietary patterns and health-related quality of life in bladder cancer survivors.

PURPOSE: A nutritious diet has been associated with better health-related quality of life (HRQOL) in a variety of cancer survivors. However, little is known about dietary habits and its association with HRQOL in bladder cancer survivors. The objective of this cross-sectional study is to describe dietary intake patterns and its relationship to HRQOL in a large cohort of bladder cancer survivors. METHODS: Bladder cancer survivors within our institutional database were mailed surveys to assess dietary intake patterns utilizing the Diet History Questionnaire II and assessing HRQOL utilizing the Functional Assessment of Cancer Therapy-Bladder Cancer. Diet quality was assessed via Healthy Eating Index 2010 scores based on subjects' Diet History Questionnaire II results. Univariate and multivariate analyses of HRQOL based on diet quality were used to evaluate whether diet quality was associated with HRQOL. RESULTS: Four hundred and fifty-nine patients (48%) returned questionnaires. Mean age was 74 years, 81% were male and 28% underwent radical cystectomy. Diet quality and quantity in our cohort was similar to the general older U.S. population and did not differ significantly between those managed conservatively or long-term following cystectomy. Our cohort had low intake of whole grains and fat-soluble vitamins, particularly vitamin D. Diet quality was significantly associated with HRQOL in the univariate analysis but lost statistical significance in our multivariate analysis. Elixhauser Comorbidity Index was significantly associated with HRQOL in the multivariate analysis. CONCLUSIONS: This study demonstrates a similar diet quality of bladder cancer survivors to the older general U.S. population that, on average, "needs improvement." Dietary intake is particularly lacking in whole grain and vitamin D intake. Future studies are warranted to determine the impact on long-term outcome, but bladder cancer survivors should be counseled on the importance and benefits of adherence to dietary guidelines, including its potential contribution toward better HRQOL.

Physical activity patterns and associations with health-related quality of life in bladder cancer survivors.

INTRODUCTION: Physical activity has been shown to significantly improve health-related quality of life (HRQOL) and survivorship in a variety of patients with cancer . However, little is known about the physical activity patterns of bladder cancer survivors and how these are related to HRQOL in the United States. Our objective was to describe self-reported physical activity patterns and HRQOL and examine the association between these measures in a large cohort of bladder cancer survivors. MATERIAL AND METHODS: In this cross-sectional study, long-term bladder cancer survivors identified through an institutional database were mailed a survey that included the Functional Assessment of Cancer Therapy Bladder Cancer (FACT-BL) and the International Physical Activity Questionnaire (IPAQ). Associations between HRQOL, as assessed by the FACT-BL, and physical activity, as assessed by the IPAQ, were examined by stratified analyses of HRQOL by different levels of physical activity, proportional odds ordinal logistic regression models, and local polynomial regression models. RESULTS: A total of 472 subjects (49% response rate) completed the survey. The mean age was 74 years; 81% were male and 87% were white. The median total weekly physical activity was 2,794 MET-min. Subjects reporting "high" physical activity had a median FACT-BL score of 129 compared with 119 among those reporting "low" physical activity, a statistically and clinically significant difference. Similarly, subjects reporting "high" physical activity had a 2.2-fold increased odds of reporting higher global HRQOL compared with subjects reporting "low" physical activity. CONCLUSIONS: This large cohort of bladder cancer survivors reported high levels of physical activity. Physical activity was positively associated with HRQOL. Further studies investigating the causal relationship between physical activity and HRQOL in the posttreatment setting in bladder cancer survivors are warranted.

Urinary NID2 and TWIST1 methylation to augment conventional urine cytology for the detection of bladder cancer.

BACKGROUND: Abnormal methylation of urinary TWIST1 and NID2 conferred high sensitivity and specificity for the detection of urothelial carcinoma. OBJECTIVE: We examine the performance of the urine-based TWIST1/NID2 methylation assay with the addition of urine cytology for the detection of urothelial carcinoma. MATERIALS AND METHODS: A prospective multi-institutional study was conducted to assess the performance of a methylation assay for patients with hematuria or under surveillance for non-muscle invasive bladder cancer (NMIBC). All patients underwent cystoscopy, a methylation assay, and cytology. Receiver operator characteristic (ROC) curves were constructed for cytology alone, the methylation assay alone, and a combined model. Areas under the curve (AUC) were compared using likelihood ratio tests. RESULTS: A total of 172 patients were enrolled (37% for hematuria and 63% NMIBC). The AUC for cytology alone with equivocal cytologies positive was 0.704, and improved to 0.773 with the addition of the DNA methylation assay (p < 0.001). When the equivocal cytologies were considered negative, the AUC improved from 0.558 to 0.697 with the addition of the DNA methylation assay (p = 0.003). CONCLUSIONS: Addition of a TWIST1/NID2-based DNA methylation assay adds diagnostic value to urine cytology and the model is sensitive to the classification of equivocal cytology.

Anticipatory Positive Urine Tests for Bladder Cancer.

PURPOSE: The aim of this study was to establish the criteria defining an anticipatory positive test for bladder cancer. METHODS: We reviewed all patients at our institution who underwent urine cytology or UroVysion fluorescence in situ hybridization (FISH) and cystoscopy from 2003 to 2012. Test performance and cancer anticipation was assessed using generalized linear mixed models, mixed-effects proportional hazards models, and cumulative incidence curves using tests performed within 30 days of each other as well as within a lag time of 1 year. RESULTS: Overall, 6729 urine tests (4729 cytology and 2040 UroVysion FISH) were paired with gold-standard cystoscopies. Sensitivity and specificity were 63 and 41% for cytology, and 37 and 84% for UroVysion FISH, respectively. A 1-year lag time allowed for cancer anticipation and neither test improved. Among patients with positive cytology and initially negative cystoscopy, the hazard ratio of developing a bladder tumor at 1 year was 1.83; 76% of these patients developed a tumor within 1 year. Similarly, among patients with a positive FISH and initially negative cystoscopy, the hazard ratio of developing a bladder tumor at 1 year was 1.56; 40% of these patients developed a tumor within 1 year. CONCLUSIONS: Urine-based tests for bladder cancer are frequently falsely positive. With further follow-up time, some of these false positive tests are vindicated as true (anticipatory) positive tests, although many will remain false positives. We developed statistical criteria to determine if a test anticipates future cancers or not.

Reporting Bias Leading to Discordant Venous Thromboembolism Rates in the United States Versus Non-US Countries Following Radical Cystectomy: A Systematic Review and Meta-analysis.

CONTEXT: Postcystectomy bladder cancer (BCa) patients are at high risk for developing venous thromboembolism (VTE). The literature varies widely in the reporting of VTE in this population. OBJECTIVE: To determine the VTE rate in subjects undergoing radical cystectomy (RC) and highlight specific factors affecting this rate. EVIDENCE ACQUISITION: This meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database, registration number: CRD42015016776. We queried MEDLINE, the Cochrane Library, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Search terms captured BCa, RC, and VTE. Per the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, abstracts were reviewed for inclusion/exclusion criteria by two reviewers, and disagreements were resolved by a third reviewer. A search of the gray literature and references of pertinent articles was also performed. The date of our last search was December 15, 2014. For unreported data, authors were contacted. Data were abstracted in duplicate and pooled using a random effects (RE) model. Subgroup analyses and meta-regression were performed to determine risk factors for VTE. EVIDENCE SYNTHESIS: We identified 2927 publications, of which 223 met inclusion criteria for this review. A total of 1 115 634 surgeries were performed on patient population (80% men) with a total of 51 908 VTEs. The VTE rate estimated by the RE model was 3.7%. Due to significant heterogeneity, subgroup and meta-regression analyses were undertaken. These revealed a higher rate of VTE in US studies at 4.49% compared with "westernized" non-US studies at 3.43% and "nonwesternized" non-US based studies at 2.50%. Other important modifiers included minimally invasive surgery at 5.54% versus open surgery at 3.55%, and age. The case-fatality rate of pulmonary emboli was 44%. CONCLUSIONS: VTE is common in patients undergoing RC. Reporting of VTE is heterogeneous and the rate varies according to study-level factors, including surgery type and country of origin. Limitations of this study include the preponderance of observational studies in the final analysis and lack of complete reporting of all variables of interest within each study. PATIENT SUMMARY: In this review, we determined the venous thromboembolism (VTE) rate in postsurgical bladder cancer patients. VTE events did vary significantly among certain subgroups.

The diagnostic accuracy of urine-based tests for bladder cancer varies greatly by patient.

BACKGROUND: Spectrum effects refer to the phenomenon that test performance varies across subgroups of a population. When spectrum effects occur during diagnostic testing for cancer, difficult patient misdiagnoses can occur. Our objective was to evaluate the effect of test indication, age, gender, race, and smoking status on the performance characteristics of two commonly used diagnostic tests for bladder cancer, urine cytology and fluorescence in situ hybridization (FISH). METHODS: We assessed all subjects who underwent cystoscopy, cytology, and FISH at our institution from 2003 to 2012. The standard diagnostic test performance metrics were calculated using marginal models to account for clustered/repeated measures within subjects. We calculated test performance for the overall cohort by test indication as well as by key patient variables: age, gender, race, and smoking status. RESULTS: A total of 4023 cystoscopy-cytology pairs and 1696 FISH-cystoscopy pairs were included in the analysis. In both FISH and cytology, increasing age, male gender, and history of smoking were associated with increased sensitivity and decreased specificity. FISH performance was most impacted by age, with an increase in sensitivity from 17 % at age 40 to 49 % at age 80. The same was true of cytology, with an increase in sensitivity from 50 % at age 40 to 67 % at age 80. Sensitivity of FISH was higher for a previous diagnosis of bladder cancer (46 %) than for hematuria (26 %). Test indication had no impact on the performance of cytology and race had no significant impact on the performance of either test. CONCLUSIONS: The diagnostic performance of urine cytology and FISH vary significantly according to the patient demographic in which they were tested. Hence, the reporting of spectrum effects in diagnostic tests should become part of standard practice. Patient-related factors must contextualize the clinicians' interpretation of test results and their decision-making.

High rates of venous thromboembolic events in patients undergoing systemic therapy for urothelial carcinoma: A systematic review and meta-analysis.

BACKGROUND: Patients undergoing systemic therapy for urothelial carcinoma (UC) are at increased risk for venous thromboembolic (VTE) events. The objective of the current study was to determine the rate of VTE events in patients undergoing systemic therapy for UC and assess factors affecting this rate. METHODS: This study was registered with the PROSPERO database (CRD42015025774). We searched Pubmed, MEDLINE, EMBASE, The Cochrane Library, CINAHL, and Web of Science libraries through August 2014. As per PRISMA guidelines, 2 reviewers independently reviewed titles and abstracts. Disagreements were arbitrated by a third reviewer. After full text review, data were abstracted and pooled using a random effects model. Authors were contacted for clarification of data. To determine VTE risk factors, subgroup analyses and meta-regression were conducted. RESULTS: We identified 3,635 publications in the initial search, of which 410 met inclusion criteria for full text review. Of these, we were able to obtain data on the outcome of interest for 62 publications. A total of 5,082 patients, of which 77% were male, underwent systemic therapy for UC, with 373 VTE events. The proportion of patients who had had prior surgery, chemotherapy, or radiation was 55%, 25%, and 9%, respectively. Fixed effects and random effects models were used to estimate the VTE rate, yielding event rates of 6.7% and 5.4%, respectively. CONCLUSIONS: VTE occurs frequently in patients undergoing systemic therapy for UC. The VTE rate was affected by the country of origin, history of radiation, as well as by the systemic treatment class. The study was limited by the incomplete reporting of all variables of interest.

A systematic review of regional hyperthermia therapy in bladder cancer.

CONTEXT: Bladder cancer therapy remains suboptimal as morbidity and mortality remain high amongst those with non-muscle-invasive and muscle-invasive disease. Regional hyperthermia therapy (RHT) is a promising adjunctive therapy being tested in multiple clinical contexts. OBJECTIVE: The aim of this study was to systematically review the literature on the efficacy and toxicity of RHT. EVIDENCE ACQUISITION: This systematic review was registered with the PROSPERO database (Registration number: CRD42015025780) and was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We queried PubMed, EMBASE, and Cochrane libraries. Two reviewers reviewed abstracts independently and a third reviewer arbitrated disagreements. The last search was performed on 28 August 2015. A descriptive analysis was performed and quality assessment was conducted using the Newcastle-Ottawa Quality Assessment Scale for observational studies, and the Cochrane Risk of Bias Assessment Tool for trials. EVIDENCE SYNTHESIS: We identified 859 publications in the initial search, of which 24 met inclusion criteria for full-text review. Of these, we were able to obtain data on the outcomes of interest for 15 publications. CONCLUSIONS: The review underscores the limited nature of the evidence; definitive conclusions are elusive. However, the promising results of RHT in the setting of intravesical chemotherapy, chemotherapy and radiotherapy show a trend towards legitimate efficacy.

Lifestyle factors and health-related quality of life in bladder cancer survivors: a systematic review.

PURPOSE: Diet, physical activity, and smoking cessation are modifiable lifestyle factors that have been shown to improve health-related quality of life (HRQOL) in many cancer survivors. Our objective was to systematically review the literature on the associations between lifestyle factors, namely diet, physical activity, smoking status, and HRQOL in bladder cancer survivors. METHODS: We queried PubMed, EMBASE, and Cochrane libraries. Two reviewers reviewed abstracts independently, and a third reviewer arbitrated disagreements. A descriptive analysis was performed. Quality assessment was conducted using the Newcastle-Ottawa Quality Assessment Scale for observational studies and the Cochrane Risk of Bias Tool for clinical trials. RESULTS: We identified 1167 publications in the initial search, of which 9 met inclusion criteria for full-text review. We were able to obtain data on the outcomes of interest for 5 publications. A total of 1288 patients who underwent treatment for bladder cancer were included. Three studies were observational by design and two were randomized controlled trials. Physical activity was addressed by 4 studies, smoking status by 2 studies, and diet by 1 study. CONCLUSIONS: The review highlights the limited evidence around lifestyle factors and quality of life in bladder cancer survivors. There is some evidence for a positive association between HRQOL and physical activity, but insufficient evidence upon which to draw conclusions about the effects of consuming fruits and vegetables or non-smoking. IMPLICATIONS FOR CANCER SURVIVORS: There is limited evidence to support a positive association between health-related quality of life and physical activity, but insufficient evidence upon which to base any conclusions about consumption of fruits and vegetables or smoking cessation in bladder cancer survivors.

Reporting Bias Leading to Discordant Venous Thromboembolism Rates in the United States Versus Non-US Countries Following Radical Cystectomy: A Systematic Review and Meta-analysis.

CONTEXT: Postcystectomy bladder cancer (BCa) patients are at high risk for developing venous thromboembolism (VTE). The literature varies widely in the reporting of VTE in this population. OBJECTIVE: To determine the VTE rate in subjects undergoing radical cystectomy (RC) and highlight specific factors affecting this rate. EVIDENCE ACQUISITION: This meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database, registration number: CRD42015016776. We queried MEDLINE, the Cochrane Library, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Search terms captured BCa, RC, and VTE. Per the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, abstracts were reviewed for inclusion/exclusion criteria by two reviewers, and disagreements were resolved by a third reviewer. A search of the gray literature and references of pertinent articles was also performed. The date of our last search was December 15, 2014. For unreported data, authors were contacted. Data were abstracted in duplicate and pooled using a random effects (RE) model. Subgroup analyses and meta-regression were performed to determine risk factors for VTE. EVIDENCE SYNTHESIS: We identified 2927 publications, of which 223 met inclusion criteria for this review. A total of 1 115 634 surgeries were performed on patient population (80% men) with a total of 51 908 VTEs. The VTE rate estimated by the RE model was 3.7%. Due to significant heterogeneity, subgroup and meta-regression analyses were undertaken. These revealed a higher rate of VTE in US studies at 4.49% compared with "westernized" non-US studies at 3.43% and "nonwesternized" non-US based studies at 2.50%. Other important modifiers included minimally invasive surgery at 5.54% versus open surgery at 3.55%, and age. The case-fatality rate of pulmonary emboli was 44%. CONCLUSIONS: VTE is common in patients undergoing RC. Reporting of VTE is heterogeneous and the rate varies according to study-level factors, including surgery type and country of origin. Limitations of this study include the preponderance of observational studies in the final analysis and lack of complete reporting of all variables of interest within each study. PATIENT SUMMARY: In this review, we determined the venous thromboembolism (VTE) rate in postsurgical bladder cancer patients. VTE events did vary significantly among certain subgroups.

Multi-institutional external validation of urinary TWIST1 and NID2 methylation as a diagnostic test for bladder cancer.

OBJECTIVES: We previously reported a clinical trial in which we were unable to replicate the excellent diagnostic metrics produced in the developmental study of the TWIST1 and NID2 gene methylation assay. In this expanded trial with subjects enrolled from another institution, we reexamine the diagnostic capabilities of the test to externally validate our previous study. MATERIALS AND METHODS: TWIST1 and NID2 gene methylation was assessed in DNA isolated from the urine of subjects at risk of bladder cancer undergoing cystoscopy for hematuria or bladder cancer surveillance. The diagnostic gold standard was cystoscopy. Two thresholds of TWIST1 and NID2 gene methylation were used for determining test result positivity, those published by Renard et al. and Abern et al. The sensitivity, specificity, positive and negative predictive values, diagnostic likelihood ratios, and receiver operating characteristic curves were calculated for each gene, as well as their combination. In all, 3 methods were used to combine TWIST1 and NID2 into a single composite test: (1) believe-the-positive decision rule-if either gene is methylated the test result is positive, which maximizes test sensitivity; (2) believe-the-negative decision rule-if either gene is not methylated the test result is negative, which maximizes test specificity; and (3) a likelihood-based logistic regression model approach that balances sensitivity and specificity. Clinical utility was determined using a decision curve analysis. RESULTS: A total of 209 subjects were evaluated: 40% for hematuria and 60% for bladder cancer surveillance. Approximately 75% were male, most of the prior cancers being low-grade Ta. Using cystoscopy as the gold standard, areas under the curve were 0.67 for TWIST1, 0.64 for NID2, and 0.66 for combined TWIST1 and NID2. Decision rule results revealed optimization of sensitivity at 67% using Renard thresholds and specificity using the Abern thresholds at 69%. We found improved sensitivity (78%) in current smokers. Decision curve analyses revealed that the methylation assay provided only a modest benefit even at high probabilities of missed cancer. CONCLUSION: A urine DNA test measuring TWIST1 and NID2 methylation was externally examined with a larger cohort and its results continue to be poor. These 2 biomarkers are unlikely to replace cystoscopy, but they may be worthy of study in active smokers.