Adverse Event Assessment of Antimuscarinics for Treating Overactive Bladder: A Network Meta-Analytic Approach

BACKGROUND: Overactive bladder (OAB) affects the lives of millions of people worldwide and antimuscarinics are the pharmacological treatment of choice. Meta-analyses of all currently used antimuscarinics for treating OAB found similar efficacy, making the choice dependent on their adverse event profiles. However, conventional meta-analyses often fail to quantify and compare adverse events across different drugs, dosages, formulations, and routes of administration. In addition, the assessment of the broad variety of adverse events is dissatisfying. Our aim was to compare adverse events of antimuscarinics using a network meta-analytic approach that overcomes shortcomings of conventional analyses. METHODS: Cochrane Incontinence Group Specialized Trials Register, previous systematic reviews, conference abstracts, book chapters, and reference lists of relevant articles were searched. Eligible studies included randomized controlled trials comparing at least one antimuscarinic for treating OAB with placebo or with another antimuscarinic, and adverse events as outcome measures. Two authors independently extracted data. A network meta-analytic approach was applied allowing for joint assessment of all adverse events of all currently used antimuscarinics while fully maintaining randomization. RESULTS: 69 trials enrolling 26'229 patients were included. Similar overall adverse event profiles were found for darifenacin, fesoterodine, transdermal oxybutynin, propiverine, solifenacin, tolterodine, and trospium chloride but not for oxybutynin orally administered when currently used starting dosages were compared. CONCLUSIONS: The proposed generally applicable transparent network meta-analytic approach summarizes adverse events in an easy to grasp way allowing straightforward benchmarking of antimuscarinics for treating OAB in clinical practice. Most currently used antimuscarinics seem to be equivalent first choice drugs to start the treatment of OAB except for oral oxybutynin dosages of ≥ 10 mg/d which may have more unfavorable adverse event profiles

Inflammation in benign prostate tissue and prostate cancer in the finasteride arm of the Prostate Cancer Prevention Trial

BACKGROUND: A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here we studied these associations in the PCPT finasteride arm. METHODS: Prostate cancer cases (N=197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N=248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of H&E stained sections. Logistic regression was used for statistical analysis. RESULTS: In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas; p < 0.001 for difference compared to placebo arm. Overall, the odds of prostate cancer did not differ by prevalence (OR=0.90, 95% CI 0.44-1.84) or extent (P-trend=0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR=1.07, 95% CI 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammationin either cases or controls. CONCLUSION: The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer. IMPACT: Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation

ProCOC: The prostate cancer outcomes cohort study

BACKGROUND: Despite intensive research over the last several decades on prostate cancer, many questions particularly those concerning early diagnosis and the choice of optimal treatment for each individual patient, still remain unanswered. The goal of treating patients with localized prostate cancer is a curative one and includes minimizing adverse effects to preserve an adequate quality of life. Better understanding on how the quality of life is affected depending on the treatment modality would assist patients in deciding which treatment to choose; furthermore, the development of prognostic biomarkers that indicate the future course of the illness is a promising approach with potential and the focus of much attention. These questions can be addressed in the context of a cohort study. METHODS/DESIGN: This is a prospective, multi-center cohort study within the canton of Zurich, Switzerland. We will include patients with newly diagnosed localized prostate cancer independently of treatment finally chosen. We will acquire clinical data including quality of life and lifestyle, prostate tissue specimen as well as further biological samples (blood and urine) before, during and after treatment for setup of a bio-bank. Assessment of these data and samples in the follow up will be done during routine controls. Study duration will be at least ten years. Influence of treatment on morbidity and mortality, including changes in quality of life, will be identified and an evaluation of biomarkers will be performed. Further we intend to set up a bio-bank containing blood and urine samples providing research of various natures around prostate cancer in the future. DISCUSSION: We presume that this study will provide answers to pertinent questions concerning prognosis and outcomes of men with localised prostate cancer

BioPrev-C – development and validation of a contemporary prostate cancer risk calculator

ObjectivesTo develop a novel biopsy prostate cancer (PCa) prevention calculator (BioPrev-C) using data from a prospective cohort all undergoing mpMRI targeted and transperineal template saturation biopsy.Materials and methodsData of all men who underwent prostate biopsy in our academic tertiary care center between 11/2016 and 10/2019 was prospectively collected. We developed a clinical prediction model for the detection of high-grade PCa (Gleason score ≥7) based on a multivariable logistic regression model incorporating age, PSA, prostate volume, digital rectal examination, family history, previous negative biopsy, 5-alpha-reductase inhibitor use and MRI PI-RADS score. BioPrev-C performance was externally validated in another prospective Swiss cohort and compared with two other PCa risk-calculators (SWOP-RC and PBCG-RC).ResultsOf 391 men in the development cohort, 157 (40.2%) were diagnosed with high-grade PCa. Validation of the BioPrev C revealed good discrimination with an area under the curve for high-grade PCa of 0.88 (95% Confidence Interval 0.82-0.93), which was higher compared to the other two risk calculators (0.71 for PBCG and 0.84 for SWOP). The BioPrev-C revealed good calibration in the low-risk range (0 - 0.25) and moderate overestimation in the intermediate risk range (0.25 - 0.75). The PBCG-RC showed good calibration and the SWOP-RC constant underestimation of high-grade PCa over the whole prediction range. Decision curve analyses revealed a clinical net benefit for the BioPrev-C at a clinical meaningful threshold probability range (≥4%), whereas PBCG and SWOP calculators only showed clinical net benefit above a 30% threshold probability.ConclusionBiopPrev-C is a novel contemporary risk calculator for the prediction of high-grade PCa. External validation of the BioPrev-C revealed relevant clinical benefit, which was superior compared to other well-known risk calculators. The BioPrev-C has the potential to significantly and safely reduce the number of men who should undergo a prostate biopsy

Metabolomics: A Novel Approach to Early and Noninvasive Prostate Cancer Detection

Prostate cancer (PCa) is the most commonly diagnosed visceral cancer in men and is responsible for the second highest cancer-related male mortality rate in Western countries, with increasing rates being reported in Korea, Japan, and China. Considering the low sensitivity of prostate-specific antigen (PSA) testing, it is widely agreed that reliable, age-independent markers of the presence, nature, and progression of PCa are required to facilitate diagnosis and timely treatment. Metabolomics or metabonomics has recently emerged as a novel method of PCa detection owing to its ability to monitor changes in the metabolic signature, within biofluids or tissue, that reflect changes in phenotype and function. This review outlines the physiology of prostate tissue and prostatic fluid in health and in malignancy in relation to metabolomics as well as the principles underlying the methods of metabolomic quantification. Promising metabolites, metabolic profiles, and their correlation with the presence and stage of PCa are summarized. Application of metabolomics to biofluids and in vivo quantification as well as the direction of current research in supplementing and improving current methods of detection are discussed. The current debate in the urology literature on sarcosine as a potential biomarker for PCa is reviewed and discussed. Metabolomics promises to be a valuable tool in the early detection of PCa that may enable earlier treatment and improved clinical outcomes

Extracorporeal shock wave lithotripsy versus flexible ureterorenoscopy in the treatment of untreated renal calculi

Background: The reported success rates for treatments of kidney stones with either extracorporeal shock wave lithotripsy (ESWL) or flexible ureterorenoscopy (URS) are conflicting. We aimed to compare the efficacy and safety of ESWL and URS for previously untreated renal calculi. Methods: All patients treated with ESWL or URS at our tertiary care centre between 2003 and 2015 were retrospectively identified. Patients with previously untreated kidney stones and a stone diameter of 5-20 mm were included. Stone-free, freedom from reintervention and complication rates were recorded. Independent predictors of stone-free and freedom from reintervention rates were identified by multivariable logistic regression and a propensity score-matched analysis was performed. Results: A total of 1282 patients met the inclusion criteria, of whom 999 (78%) underwent ESWL and 283 (22%) had URS. During post-operative follow-up, only treatment modality and stone size could independently predict stone-free and freedom from reintervention rates. After propensity score matching, ESWL showed significantly lower stone-free rates [ESWL (71%) versus URS (84%)] and fewer patients with freedom from reintervention [ESWL (55%) versus URS (79%)] than URS. Complications were scarce for both treatments and included Clavien Grade 3a in 0.8% versus 0% and Grade 3b in 0.5% versus 0.4% of ESWL and URS treated patients, respectively. Conclusions: Treatment success was mainly dependent on stone size and treatment modality. URS might be the better treatment option for previously untreated kidney stones 5-20 mm, with similar morbidity but higher stone-free rates and fewer reinterventions than ESWL. Keywords: adverse effects; kidney calculi; lithotripsy; minimally invasive surgery; treatment outcome

The role of 11C-Choline and 18F-Fluorocholine Positron Emission Tomography (PET) and PET/CT in prostate cancer: A systematic review and meta-analysis

CONTEXT: The role of positron emission tomography (PET) and PET/computed tomography (PET/CT) in prostate cancer (PCa) imaging is still debated, although guidelines for their use have emerged over the last few years. OBJECTIVE: To systematically review and conduct a meta-analysis of the available evidence of PET and PET/CT using 11C-choline and 18F-fluorocholine as tracers in imaging PCa patients in staging and restaging settings. EVIDENCE ACQUISITION: PubMed, Embase, and Web of Science (by citation of reference) were searched. Reference lists of review articles and included articles were checked to complement electronic searches. EVIDENCE SYNTHESIS: In staging patients with proven but untreated PCa, the results of the meta-analysis on a per-patient basis (10 studies, n = 637) showed pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of 84% (95% confidence interval [CI], 68-93%), 79% (95% CI, 53-93%), and 20.4 (95% CI, 9.9-42.0), respectively. The positive and negative likelihood ratios were 4.02 (95% CI, 1.73-9.31) and 0.20 (95% CI, 0.11-0.37), respectively. On a per-lesion basis (11 studies, n = 5117), these values were 66% (95% CI, 56-75%), 92% (95% CI, 78-97%), and 22.7 (95% CI, 8.9-58.0), respectively, for pooled sensitivity, specificity, and DOR; and 8.29 (95% CI, 3.05-22.54) and 0.36 (95% CI, 0.29-0.46), respectively, for positive and negative likelihood ratios. In restaging patients with biochemical failure after local treatment with curative intent, the meta-analysis results on a per-patient basis (12 studies, n = 1055) showed pooled sensitivity, specificity, and DOR of 85% (95% CI, 79-89%), 88% (95% CI, 73-95%), and 41.4 (95% CI, 19.7-86.8), respectively; the positive and negative likelihood ratios were 7.06 (95% CI, 3.06-16.27) and 0.17 (95% CI, 0.13-0.22), respectively. CONCLUSIONS: PET and PET/CT imaging with 11C-choline and 18F-fluorocholine in restaging of patients with biochemical failure after local treatment for PCa might help guide further treatment decisions. In staging of patients with proven but untreated, high-risk PCa, there is limited but promising evidence warranting further studies. However, the current evidence shows crucial limitations in terms of its applicability in common clinical scenarios

How accurate is unenhanced multidetector-row CT (MDCT) for localization of renal calculi?

PURPOSE: To investigate the correlation between unenhanced MDCT and intraoperative findings with regard to the exact anatomical location of renal calculi. DESIGN, SETTING, AND PARTICIPANTS: Fifty-nine patients who underwent unenhanced MDCT for suspected urinary stone disease, and who underwent subsequent flexible ureterorenoscopy (URS) as treatment of nephrolithiasis were included in this retrospective study. All MDCT data sets were independently reviewed by three observers with different degrees of experience in reading CT. Each observer was asked to indicate presence and exact anatomical location of any calcification within pyelocaliceal system, renal papilla or renal cortex. Results were compared to intraoperative findings which have been defined as standard of reference. Calculi not described at surgery, but present on MDCT data were counted as renal cortex calcifications. RESULTS: Overall 166 calculi in 59 kidneys have been detected on MDCT, 100 (60.2%) were located in the pyelocaliceal system and 66 (39.8%) in the renal parenchyma. Of the 100 pyelocaliceal calculi, 84 (84%) were correctly located on CT data sets by observer 1, 62 (62%) by observer 2, and 71 (71%) by observer 3. Sensitivity/specificity was 90-94% and 50-100% if only pyelocaliceal calculi measuring >4 mm in size were considered. For pyelocaliceal calculi≤4 mm in size diagnostic performance of MDCT was inferior. CONCLUSION: Compared to flexible URS, unenhanced MDCT is accurate for distinction between pyelocaliceal calculi and renal parenchyma calcifications if renal calculi are >4 mm in size. For smaller renal calculi, unenhanced MDCT is less accurate and distinction between a pyelocaliceal calculus and renal parenchyma calcification is difficult

Influence of Varying Assessment Parameters on the Diagnostic Accuracy of Magnetic Resonance Imaging in the Local Staging of Prostate Cancer

INTRODUCTION There is a broad variability in the accuracy levels of MRI with regard to the local staging of prostate cancer (PCa). METHODS A prospective analysis was conducted in patients with localized PCa with MRI of the prostate before radical prostatectomy. MRI and pathology findings were independently reviewed and reported based on a standardized map of the prostate with 16 regions of interest (ROIs). Diagnostic accuracy analysis of the MRI was performed using varying prostate-subpart sizes and varying cutoffs for the radiological probability for PCa presence. RESULTS Seventy four patients were included. Using varying cutoff probabilities and varying sizes of prostate-subparts resulted in a broad range of sensitivity (6-88%) and specificity (38-100%). Lower probabilities of PCa presence and larger prostate-subparts resulted in higher sensitivity but lower specificity and vice versa. Best diagnostic performance was achieved by using prostate sextants and at least moderate probabilities for PCa presence; mean sensitivity and specificity were 38% (95% CI 13-75) and 95% (95% CI 88-98). CONCLUSION The use of varying assessment parameters strongly affects the diagnostic accuracy of MRI in the local staging of PCa. Hence, precise and standardized reporting regarding these parameters is important. In our study, using at least moderate probabilities for PCa presence on MRI and prostatic sextants as ROI size was associated with best diagnostic performance