Continuous saline bladder irrigation for two hours following transurethral resection of bladder tumors in patients with non-muscle invasive bladder cancer does not prevent recurrence or progression compared with intravesical Mitomycin-C.

BackgroundIntravesical Mitomycin-C (MMC) following transurethral resection of bladder tumor (TURBT), while efficacious, is associated with side effects and poor utilization. Continuous saline bladder irrigation (CSBI) has been examined as an alternative. In this study we sought to compare the rates of recurrence and/or progression in patients with NMIBC who were treated with either MMC or CSBI after TURBT.MethodsWe retrospectively reviewed records of patients with NMIBC at our institution in 2012-2015. Perioperative use of MMC (40 mg in 20 mL), CSBI (two hours), or neither were recorded. Primary outcome was time to recurrence or progression. Descriptive statistics, chi-squared analysis, Kaplan-Meier survival analysis, and Cox multivariable regression analyses were performed.Results205 patients met inclusion criteria. Forty-five (22.0%) patients received CSBI, 71 (34.6%) received MMC, and 89 (43.4%) received no perioperative therapy. On survival analysis, MMC was associated with improved DFS compared with CSBI (p = 0.001) and no treatment (p = 0.0009). On multivariable analysis, high risk disease was associated with increased risk of recurrence or progression (HR 2.77, 95% CI: 1.28-6.01), whereas adjuvant therapy (HR 0.35, 95% CI: 0.20-0.59) and MMC (HR 0.43, 95% CI: 0.25-0.75) were associated with decreased risk.ConclusionsPostoperative MMC was associated with improved DFS compared with CSBI and no treatment. The DFS benefit seen with CSBI in other studies may be limited to patients receiving prolonged irrigation. New intravesical agents being evaluated may consider saline as a control given our data demonstrating that short-term CSBI is not superior to TURBT alone

Association between Metabolic Syndrome and Recurrence of Nonmuscle Invasive Bladder Cancer following bacillus Calmette-Guérin Treatment

IntroductionIntravesical bacillus Calmette-Guérin (BCG) therapy is the gold standard adjuvant treatment for patients with high-grade non-muscle-invasive bladder cancer (NMIBC). Despite the association between metabolic syndrome (MetS) and bladder cancer, the association between MetS and BCG failure is unknown. The objective of this study was to characterize disease recurrence following BCG in patients with and without MetS.MethodsWe retrospectively evaluated the records of patients undergoing TURBT at our institution in 2012-2015 for NMIBC and identified those who received adjuvant BCG therapy. MetS was defined as having three of four components: diabetes mellitus, hyperlipidemia, hypertension, or body mass index (BMI)≥30kg/m2. The primary outcome was recurrence or progression. Descriptive statistics, chi-squared analysis, Kaplan-Meier survival analysis, and Cox multivariable regression analyses were performed.ResultsHigh grade was present in 83/90 (92.2%) patients. MetS was present in 27/90 (30%) patients. Median follow-up was 20 months. On Kaplan-Meier analysis, patients with MetS had worse DFS compared with patient without MetS. On multivariable analysis, BMI≥30 kg/m2 was a significant predictor of recurrence or progression (HR 2.94, 95% CI: 1.43-6.03). Presence of MetS did not significantly affect the type of BCG failure.ConclusionsThe association between MetS and failure to respond to BCG therapy is multifactorial but is in part associated with obesity. Elevated BMI is strongly associated with recurrence or progression. Further studies are warranted to investigate the relationship between increased adiposity and response to BCG, especially as other novel immunotherapeutic agents are likely to enter the NMIBC space

Role of cigarette smoking in urological malignancies and clinical interventions for smoking cessation

Cigarette smoking is the single greatest preventable cause of disease and death. Our literature review highlights the increased risk of cigarette smoking and kidney cancer, bladder cancer and prostate cancer

Adjuvant Therapy for High Risk Localized Kidney Cancer: Emerging Evidence and Future Clinical Trials

PurposeWe reviewed the literature on adjuvant therapies for patients with high risk localized kidney cancer following surgical resection. In this analysis we merge 2 recently published prospective trials with conflicting results within the context of their respective designs. In addition, we spotlight upcoming trials that use novel immunotherapy based checkpoint inhibitors and have the potential to establish a new standard of care.Materials and methodsWe searched PubMed® for English language articles published through January 2017 using the keywords "renal cell carcinoma," "kidney cancer," "immunotherapy," "targeted therapy" and "adjuvant therapy." ClinicalTrials.gov was queried for ongoing studies. Relevant data recently presented at major urology and medical oncology meetings are also included.ResultsAdjuvant therapies for high risk localized kidney cancer can be grouped into the categories of 1) traditional immunotherapy, 2) inhibitors of the vascular endothelial growth factor and mTOR (mammalian target of rapamycin) pathways, 3) vaccines and antibody dependent cytotoxic agents, and 4) immune checkpoint inhibitors. Several trials of traditional immunotherapy, such as interferon-α and high dose interleukin-2, failed to demonstrate benefit as adjuvant treatment and were associated with significant adverse events. Vascular endothelial growth factor and mTOR inhibitors have less severe toxicity in metastatic disease and, therefore, are natural considerations for adjuvant trials. However, current data are conflicting. The ASSURE (Sunitinib Malate or Sorafenib Tosylate in Treating Patients with Kidney Cancer that was Removed by Surgery, NCT00326898) trial found no recurrence-free survival benefit of sorafenib or sunitinib over placebo, while S-TRAC (Clinical Trial Comparing Efficacy and Safety of Sunitinib versus Placebo for the Treatment of Patients at High Risk of Recurrent Renal Cell Cancer, NCT00375674) revealed that 1 year of sunitinib improved recurrence-free survival by 1.2 years. Vaccine based treatments and antibody dependent cytotoxic agents have had mixed results. New trials evaluating immune checkpoint inhibitors are planned, given the impressive efficacy and tolerability as second line agents in metastatic disease. Future adjuvant trials are likely to be guided by molecular signatures to treat patients most likely to benefit.ConclusionsBased on the available data, there appears to be no role for traditional immunotherapy as adjuvant treatment in patients with high risk localized kidney cancer following surgical resection. S-TRAC provides evidence that 1 year of adjuvant sunitinib in patients with higher risk locoregional disease increases the median time to recurrence. However, the data on overall survival are immature and adverse effects are common. Results from trials investigating immune checkpoint inhibitors are highly anticipated

Association Between Number of Endoscopic Resections and Utilization of Bacillus Calmette-Guérin Therapy for Patients With High-Grade, Non–Muscle-Invasive Bladder Cancer

BackgroundBacillus Calmette-Guérin (BCG) is the reference standard treatment for patients with high-grade, non-muscle-invasive bladder cancer (NMIBC). We previously described noncompliance with guidelines for BCG use in patients with high-risk disease. In the current study, we sought to characterize how the number of endoscopic resections of bladder tumors affects BCG utilization using population-level data.Patients and methodsWe queried a Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to evaluate claims records of 4776 patients diagnosed with high-grade NMIBC between 1992 and 2002 and followed until 2007, who survived for at least 2 years and who did not undergo definitive treatment with cystectomy, radiotherapy, or systemic chemotherapy. We stratified patients on the basis of the number of endoscopic resections of bladder tumors. We used chi-square analysis to compare number of resections to BCG utilization and multinomial logistic regression analysis to quantify BCG utilization by patient and tumor characteristics.ResultsUtilization of BCG increases with increasing endoscopic resections from 40% at diagnosis to 72% after 6 resections. The cumulative rate of at least an induction course of BCG plateaus after 3 resections. Lower BCG utilization was associated with advanced age (≥ 80 years), while increased utilization was associated with being married, higher disease stage (Tis and T1) and grade (undifferentiated), and increasing endoscopic resections.ConclusionA significant fraction of patients with NMIBC do not receive induction BCG despite its proven benefit in minimizing recurrences. Most patients receive BCG only after multiple endoscopic resections. Strategies focused on earlier adoption of BCG to prevent recurrences instead of reacting to recurrences may limit progression and improve survival

Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines

SummaryThe concept of tumor stem cells (TSCs) provides a new paradigm for understanding tumor biology, although it remains unclear whether TSCs will prove to be a more robust model than traditional cancer cell lines. We demonstrate marked phenotypic and genotypic differences between primary human tumor-derived TSCs and their matched glioma cell lines. Unlike the matched, traditionally grown tumor cell lines, TSCs derived directly from primary glioblastomas harbor extensive similarities to normal neural stem cells and recapitulate the genotype, gene expression patterns, and in vivo biology of human glioblastomas. These findings suggest that TSCs may be a more reliable model than many commonly utilized cancer cell lines for understanding the biology of primary human tumors