Tamsulosin oral controlled absorption system (OCAS) in the treatment of benign prostatic hypertrophy

The efficacy of tamsulosin at the cost of a relatively benign side effect profile has been attributed to receptor selectivity directed at the α1a and α1d adrenergic receptor subtypes. The oral-controlled absorption system (OCAS®) represents a drug delivery refinement that incorporates a matrix of gel-forming and gel-enhancing agents to promote a constant drug release independent of environmental food or fluid. There are clinical data to support the concept that drug peaks are lessened and that drug release continues throughout the alimentary tract due to the OCAS formulation. Furthermore this equates with less adverse effects on physiologic parameters. To date however improvements in cardiovascular symptoms such as dizziness, headache and syncope have not been demonstrated in healthy men. Ejaculatory dysfunction appears less problematic with the OCAS preparation. Tamsulosin OCAS may be of greatest benefit to men with cardiovascular co-morbidities taking anti-hypertensive medications that might predispose them to symptomatic hypotensive episodes. It will be necessary to evaluate this group of men more closely in further trials to determine what they stand to gain from changing medications, and then relate this to drug costs to draw a final conclusion as to the place of tamsulosin OCAS in contemporary urological practice

Does patient age affect survival after radical cystectomy?

OBJECTIVE To analyse the impact of patient age on survival after radical cystectomy (RC). PATIENTS AND METHODS After ethics review board approval, two databases of patients with bladder cancer (BC) undergoing RC at the University Heath Network, Toronto, Canada (1992-2008) and the University of Turku, Turku, Finland (1986-2005) were retrospectively analysed. A total of 605 patients who underwent this procedure between June 1985 and March 2010 were included. Patients were divided into four age groups: = 80 years. Demographic, clinical and pathological data were compared, as well as recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OAS) rates. RESULTS Compared with younger patients (age = 80 years) had higher American Society of Anesthesiologists scores (P = 80 years (P = 80 years) should not be denied RC if they are deemed fit to undergo surgery. Senior adults do not suffer from adverse histopathological features as compared with younger patients

Systematic review and meta-analysis on trimodal therapy versus radical cystectomy for muscle-invasive bladder cancer: Does the current quality of evidence justify definitive conclusions?

OBJECTIVES To systematically review and meta-analyze the current literature in a methodologically rigorous and transparent manner for quantitative evidence on survival outcomes among patients diagnosed with muscle-invasive bladder cancer that were treated by either trimodal therapy or radical cystectomy. MATERIALS AND METHODS MEDLINE, EMBASE, CENTRAL were systematically searched for comparative observational studies reporting disease-specific survival and/or overall survival on adult patients diagnosed with localized muscle-invasive bladder cancer that were exposed to either trimodal therapy or radical cystectomy. Studies qualified for meta-analysis (random effects model) if they were not at critical risk of bias (RoB). RESULTS The literature search identified 12 eligible studies. Three (all rated as "moderate RoB") out of 6 studies reporting on disease-specific survival qualified for quantitative analysis and yielded a pooled hazard ratio (trimodal therapy versus radical cystectomy) of 1.39 (95% confidence interval: 1.03-1.88). Four (mainly rated as "serious RoB") out of 12 studies were included in the meta-analysis of overall survival and estimated a hazard ratio of 1.39 (1.20-1.59). CONCLUSION Pooled results were significant in favor of radical cystectomy. The conclusion is mainly driven by large population-based studies that are at high RoB. Hence, the certainty of these treatment estimates can be considered very low and further research will likely have an important impact on these estimates. At present, the ultimate decision between trimodal therapy and radical cystectomy should be left to the patient based on individual preferences and on the recommendation of a multidisciplinary provider team experienced with both approaches

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Treatment of bladder cancer in the elderly

As the population ages and life expectancy increases in the human population, more individuals will be diagnosed with bladder cancer (BC). The definition of who is elderly is likely to change in the future from the commonly used cut-off of ≥75 years of age. Physiological rather than chronological age is key. BC care in the elderly is likely to become a very common problem in daily practice. Concerns have been raised that senior BC patients are not given treatments that could cure their disease. Clinicians lack quantitative and reliable estimates of competing mortality risks when considering treatments for BC. Majority of patients diagnosed with BC are elderly, making treatment decisions complex with their increasing number of comorbidities. A multidisciplinary approach to these patients may be a way to incorporate discussion from various disciplines regarding treatment options available. Here we review various treatment options for elderly patients with muscle invasive BC and nonmuscle invasive BC. We include differences in treatments from robotic versus open radical cystectomy, various urinary diversion techniques, chemotherapy, radiation therapy and combination treatments. In clinical practice, treatment decisions for elderly patients should be done on a case-bycase basis, tailored to each patient with their specific histories and comorbidities considered. Some healthy elderly patients may be better candidates for extensive curative treatments than their younger counterparts. This implies that these important, life-altering decisions cannot be solely based on age as many other factors can affect patient survival outcomes