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

Objectives: To 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 methods: Data 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). Results: Of 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. Conclusion: BiopPrev-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.

Top Ten Tips Palliative Care Clinicians Should Know About Urological Care.

Patients receiving palliative care (PC) can present with or develop a host of urological needs or complications. These needs can include attention to sexual health, urinary incontinence, genitourinary bleeding, and urinary tract obstruction by benign, malignant, or urinary stone diseases. These varied conditions require that PC clinicians understand invasive and noninvasive medical, surgical, and radiation options for treatment. This article, written by a team of urologists, geriatricians, and PC specialists, offers information and guidance to PC teams in an accessible "Top Ten Tips" format to increase comfort with and skills around assessment, evaluation, and specialist referral for urological conditions common in the PC setting.

Promoting continence in older people.

The prevalence of urinary incontinence (UI) is strongly associated with increasing age. Twenty five percent of women over 80 years of age have clinically significant symptoms in population surveys, but prevalence is as high as 70% in older hospital in-patients and residents of care homes with nursing. UI substantially affects quality of life and well-being, and generates significant economic burden for health and social care. Sadly, UI is considered as taboo by society, leading to isolation, depression and reluctance to seek help. As with all aspects of care of older people, a multi-modal approach to assessment and management is needed. Key to effective management of incontinence is recognition. As a minimum, clinicians should actively ask patients about continence, especially in older adults living with frailty. Careful evaluation and establishment of any underpinning diagnosis and aetiological factors requires comprehensive, multimodal, usually multidisciplinary, assessment. A lack of awareness of the problem and what can be done about it exists in both laypeople and clinicians, this needs correcting. An interdisciplinary approach to research and management must be the way into the future.

[Urinary stone disease - size isn't all that matters]. / Urolithiasis.

Urinary stone disease - size isn't all that matters Abstract. Urinary stone disease is a very frequent disease with a life-time-risk of about 10 - 15 % in industrialized countries. Meanwhile mostly asymptomatic stone formation takes place within the renal pelvic system (renal stone disease), the typical clinical manifestation results when these stones enter and consequently obstruct the ureter (ureteral stone disease). Hence, in case of acute flank pain, ureteral stone disease is one of the most important differential diagnosis and requires always an immediate as well as accurate diagnostic work up. In here, CT-scans have shown to be most accurate and outperform ultrasound, especially concerning the overall assessment of the stone situation in the patient. Beside the diagnosis of the stone disease, the medical history, vital signs as well as blood and urinary tests are of importance in the primary work up of the patient since the identification of a potential concurrent infection within the urinary tract is of highest importance. Both, renal stone disease (mostly asymptomatic) as well as ureteral stone disease (often associated with acute and destructive flank pain) are usually not associated with an immediate threat. Ureteral stone disease with a concurrent urinary tract infection in contrary is one of the most dangerous situations in urology and, if missed, associated with urosepsis and high morbidity even lethality. The immediate drainage of the obstructed and infected urinary tract is the most important emergency action in these patients.

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

[This corrects the article DOI: 10.1093/ckj/sfx151.].

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.

The German version of the Expanded Prostate Cancer Index Composite (EPIC): translation, validation and minimal important difference estimation.

BACKGROUND: No official German translation exists for the 50-item Expanded Prostate Cancer Index Composite (EPIC), and no minimal important difference (MID) has been established yet. The aim of the study was to translate and validate a German version of the EPIC with cultural adaptation to the different German speaking countries and to establish the MID. METHODS: We translated and culturally adapted the EPIC into German. For validation, we included a consecutive subsample of 92 patients with localized prostate cancer undergoing radical prostatectomy who participated the Prostate Cancer Outcomes Cohort. Baseline and follow-up assessments took place before and six weeks after prostatectomy in 2010 and 2011. We assessed the EPIC, EORTC QLQ-PR25, Feeling Thermometer, SF-36 and a global rating of health state change variable. We calculated the internal consistency, test-retest reliability, construct validity, responsiveness and MID. RESULTS: For most EPIC domains and subscales, our a priori defined criteria for reliability were fulfilled (construct reliability: Cronbach's alpha 0.7-0.9; test-retest reliability: intraclass-correlation coefficient ≥ 0.7). Cross-sectional and longitudinal correlations between EPIC and EORTC QLQ-PR25 domains ranged from 0.14-0.79, and 0.06-0.5 and 0.08-0.72 for Feeling Thermometer and SF-36, respectively. We established MID values of 10, 4, 12, and 6 for the urinary, bowel, sexual and hormonal domain. CONCLUSION: The German version of the EPIC is reliable, responsive and valid to measure HRQL in prostate cancer patients and is now available in German language. With the suggested MID we provide interpretation to what extent changes in HRQL are clinically relevant for patients. Hence, study results are of interest beyond German speaking countries.

Prevalence and causes of abnormal PSA recovery.

BACKGROUND: Prostate-specific antigen (PSA) test is of paramount importance as a diagnostic tool for the detection and monitoring of patients with prostate cancer. In the presence of interfering factors such as heterophilic antibodies or anti-PSA antibodies the PSA test can yield significantly falsified results. The prevalence of these factors is unknown. METHODS: We determined the recovery of PSA concentrations diluting patient samples with a standard serum of known PSA concentration. Based on the frequency distribution of recoveries in a pre-study on 268 samples, samples with recoveries <80% or >120% were defined as suspect, re-tested and further characterized to identify the cause of interference. RESULTS: A total of 1158 consecutive serum samples were analyzed. Four samples (0.3%) showed reproducibly disturbed recoveries of 10%, 68%, 166% and 4441%. In three samples heterophilic antibodies were identified as the probable cause, in the fourth anti-PSA-autoantibodies. The very low recovery caused by the latter interference was confirmed in serum, as well as heparin- and EDTA plasma of blood samples obtained 6 months later. Analysis by eight different immunoassays showed recoveries ranging between <10% and 80%. In a follow-up study of 212 random plasma samples we found seven samples with autoantibodies against PSA which however did not show any disturbed PSA recovery. CONCLUSIONS: About 0.3% of PSA determinations by the electrochemiluminescence assay (ECLIA) of Roche diagnostics are disturbed by heterophilic or anti-PSA autoantibodies. Although they are rare, these interferences can cause relevant misinterpretations of a PSA test result.

Prognostic Role of Preoperative Serum Lipid Levels in Patients Undergoing Radical Prostatectomy for Clinically Localized Prostate Cancer.

BACKGROUND: The prognostic role of preoperative serum lipid levels in patients undergoing radical prostatectomy (RP) for clinically localized prostate cancer (PCa) is unclear. The aim of the present study was to investigate preoperative serum lipid levels in patients with clinically localized PCa undergoing RP and their association with clinicopathological features and oncological outcome. METHODS: Preoperative lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) and statin use from consecutive patients with clinically localized PCa undergoing RP in a tertiary referral center between 2008 and 2015 were recorded and patients were followed prospectively. Logistic regression analysis was used to test the association between lipid levels and clinicopathological parameters. Lipid values were analyzed both as continuous and dichotomized variables. Univariable and multivariable Cox regression analyses were performed to identify predictors for recurrence-free survival (RFS). Recurrence was defined as rising and verified PSA levels >0.1 ng/ml. RESULTS: Our cohort consisted of 371 men with a median age of 63 years (range 41-78 years) and a median preoperative PSA value of 6.79 ng/ml (0.43-81.4 ng/ml). Median follow-up was 28 months (1-64). No association was found between lipid levels and adverse pathological characteristics such as ≥pT3, Gleason score ≥8, positive nodal status and positive surgical margins. Recurrence occurred in 49 patients (15.4%) at a median time of 18 months (2-51 month). Compared to low LDL cholesterol, high LDL cholesterol was associated with longer RFS in univariable analysis (continuous: Hazard Ratio (HR): 0.67, 95%-Confidence Interval (CI): 0.47-0.96, P = 0.03; 3 mM cut-point: HR: 0.44, 95%-CI: 0.24-0.79, P = 0.006). Neither levels of other lipids, nor statin use were associated with RFS. Preoperative LDL cholesterol remained an independent predictor for PCa recurrence in a multivariable model adjusted for age, preoperative PSA, statin use, tumor stage, Gleason score, nodal status and surgical margin status (continuous: HR: 0.66, 95%-CI: 0.44-0.99, P = 0.04; 3 mM cut-point: HR: 0.41, 95%-CI: 0.21-0.78, P = 0.007). CONCLUSIONS: This is the first prospective study showing the potential adverse and independent prognostic role of low preoperative LDL cholesterol levels in patients with localized PCa undergoing RP. Prostate 77:549-556, 2017. © 2017 Wiley Periodicals, Inc.

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 hematoxylin and eosin-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 with placebo arm). Overall, the odds of prostate cancer did not differ by prevalence [OR, 0.90; 95% confidence interval (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 inflammation in 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.

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.

Bilaterally positive biopsy cores are associated with non-organ-confined disease in prostate cancer patients eligible for active surveillance.

PURPOSE: To investigate the association between the laterality of diagnostic prostate cancer-positive biopsy cores and definitive tumor stage on final pathology (organ-confined versus non-organ-confined). PATIENTS AND METHODS: This is a retrospective analysis of 165 men after radical prostatectomy fulfilling our active surveillance criteria at the time of surgery. Nominal variables were compared using Fisher's exact test, continuous variables using Mann-Whitney test. Odds ratios including 95% Wald and probabilities including 95% Wilson confidence intervals are provided. RESULTS: 5 (3%) patients had non-organ-confined disease: 2 out of 144 (1%) patients with unilateral and 3 out of 17 (18%) patients with bilateral cancer-positive biopsy cores (p = 0.009). The estimated odds ratio for non-organ-confined disease was 14.67 (95% confidence interval 1.55-189.23) for patients with bilateral compared to patients with unilateral cancer-positive biopsy cores. The sensitivity, specificity and accuracy of bilaterally positive biopsies as an additional criterion to identify non-organ-confined disease are 60, 91 and 90%, respectively. CONCLUSION: In our cohort, patients with bilaterally positive biopsy cores were significantly more likely to harbor a non-organ-confined tumor than patients with unilaterally positive cores. Due to their high specificity, bilaterally positive biopsies may represent a reasonable exclusion criterion for active surveillance if our results are corroborated in further studies.

Serum prostate-specific antigen (PSA) concentration is positively associated with rate of disease reclassification on subsequent active surveillance prostate biopsy in men with low PSA density.

OBJECTIVE: To investigate the association between serum prostate-specific antigen (PSA) concentration at active surveillance (AS) entry and disease reclassification on subsequent AS biopsy ('biopsy reclassification') in men with low PSA density (PSAD). To investigate whether a clinically meaningful PSA threshold for AS eligibility/ineligibility for men with low PSAD can be identified based on risk of subsequent biopsy reclassification. PATIENTS AND METHODS: We included men enrolled in the Johns Hopkins AS Study (JHAS) who had a PSAD of <0.15 ng/mL/g (640 men). We estimated the incidence rates (IRs; per 100 person years) and hazard ratios (HR) of biopsy reclassification (Gleason score ≥ 7, any Gleason pattern 4 or 5, ≥3 positive cores, or ≥50% cancer involvement/biopsy core) for categories of serum PSA concentration at the time of entry into AS. We generated predicted IRs using Poisson regression to adjust for age and prostate volume, mean percentage free PSA (ratio of free to total PSA) and maximum percentage biopsy core involvement with cancer. RESULTS: The unadjusted IRs (per 100 person years) of biopsy reclassification across serum PSA concentration at entry into JHAS showed, in general, an increase; however, the pattern was not linear with higher IRs in the group ≥ 4 to <6 ng/mL (14.2, 95% confidence interval [CI] 11.8-17.2%) when compared with ≥6 to <8 ng/mL (8.4, 95% CI 5.7-12.3%) but almost similar IRs when compared with the group ≥ 8 to <10 ng/mL (14.8, 95% CI 8.4-26.1%). The adjusted predicted IRs of reclassification showed a similar non-linear increase in IRs, whereby the rates around 4 ng/mL were similar to the rates around 10 ng/mL. CONCLUSION: Risk for biopsy reclassification increased non-linearly across PSA concentration in men with low PSAD, whereby no obvious clinically meaningful threshold could be identified. This information could be incorporated into decision-making for AS. However, longer follow-up times are needed to warrant final conclusions.

All that glitters isn't gold: a survey on acknowledgment of limitations in biomedical studies.

BACKGROUND: Acknowledgment of all serious limitations to research evidence is important for patient care and scientific progress. Formal research on how biomedical authors acknowledge limitations is scarce. OBJECTIVES: To assess the extent to which limitations are acknowledged in biomedical publications explicitly, and implicitly by investigating the use of phrases that express uncertainty, so-called hedges; to assess the association between industry support and the extent of hedging. DESIGN: We analyzed reporting of limitations and use of hedges in 300 biomedical publications published in 30 high and medium -ranked journals in 2007. Hedges were assessed using linguistic software that assigned weights between 1 and 5 to each expression of uncertainty. RESULTS: Twenty-seven percent of publications (81/300) did not mention any limitations, while 73% acknowledged a median of 3 (range 1-8) limitations. Five percent mentioned a limitation in the abstract. After controlling for confounders, publications on industry-supported studies used significantly fewer hedges than publications not so supported (p = 0.028). LIMITATIONS: Detection and classification of limitations was--to some extent--subjective. The weighting scheme used by the hedging detection software has subjective elements. CONCLUSIONS: Reporting of limitations in biomedical publications is probably very incomplete. Transparent reporting of limitations may protect clinicians and guideline committees against overly confident beliefs and decisions and support scientific progress through better design, conduct or analysis of new studies.

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.

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.

Combined magnetic resonance imaging and magnetic resonance spectroscopy imaging in the diagnosis of prostate cancer: a systematic review and meta-analysis.

CONTEXT: Magnetic resonance imaging (MRI) combined with magnetic resonance spectroscopy imaging (MRSI) emerged as a promising test in the diagnosis of prostate cancer and showed encouraging results. OBJECTIVE: The aim of this systematic review is to meta-analyse the diagnostic accuracy of combined MRI/MRSI in prostate cancer and to explore risk profiles with highest benefit. EVIDENCE ACQUISITION: The authors searched the MEDLINE and EMBASE databases and the Cochrane Library, and the authors screened reference lists and contacted experts. There were no language restrictions. The last search was performed in August 2008. EVIDENCE SYNTHESIS: We identified 31 test-accuracy studies (1765 patients); 16 studies (17 populations) with a total of 581 patients were suitable for meta-analysis. Nine combined MRI/MRSI studies (10 populations) examining men with pathologically confirmed prostate cancer (297 patients; 1518 specimens) had a pooled sensitivity and specificity on prostate subpart level of 68% (95% CI, 56-78%) and 85% (95% CI, 78-90%), respectively. Compared with patients at high risk for clinically relevant cancer (six studies), sensitivity was lower in low-risk patients (four studies) (58% [46-69%] vs 74% [58-85%]; p>0.05) but higher for specificity (91% [86-94%] vs 78% [70-84%]; p<0.01). Seven studies examining patients with suspected prostate cancer at combined MRI/MRSI (284 patients) had an overall pooled sensitivity and specificity on patients level of 82% (59-94%) and 88% (80-95%). In the low-risk group (five studies) these values were 75% (39-93%) and 91% (77-97%), respectively. CONCLUSIONS: A limited number of small studies suggest that MRI combined with MRSI could be a rule-in test for low-risk patients. This finding needs further confirmation in larger studies and cost-effectiveness needs to be established.

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.