Lifestyle aspects in a contemporary middle-European cohort of patients undergoing androgen deprivation therapy for advanced prostate cancer: data from the non-interventional LEAN study.

Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with significant side effects. With the transition of PCa from a foudroyant course to a chronic disease, managing these side effects has become increasingly important. There is growing evidence that nutritional changes and physical activity are beneficial in these patients. Here we examine the impact of written patient information on the physical activity and dietary habits of PCa patients receiving ADT and behaviour changes between baseline and 1 year, in the open-label, non-interventional LEAN study. In total, 959 patients with advanced hormone-sensitive PCa requiring ADT with the Leuprorelin Sandoz® implant were included from January 2014 to July 2015 and followed for ≥ 12 months. At the start of the study, urologists received a questionnaire concerning the written information provided to patients regarding their disease, patient advocacy groups, diet and physical activity. Patients received a questionnaire on their dietary habits and physical activity at the start and end of the study. Urologists from 147 study centres and 540 patients responded to the questionnaires. While 69 % of these patients received disease-specific information, only 30 % and 17 % received information regarding nutrition and physical activity, respectively. The majority of urologists estimate that their patients rarely or never follow guidance on nutrition or physical activity, yet > 90 % of patients indicate they would make use of this information, if provided. Few patients showed behavioural changes between baseline and 1 year without evident differences between patients that received information and those that did not.

Effectiveness and Distribution of Testosterone Levels within First Year of Androgen Deprivation Therapy in a Real-World Setting: Results from the Non-Interventional German Cohort LEAN Study.

BACKGROUND: Observational studies generate information on real-world therapy and complement data from prospective randomized trials. LEAN is an open-label, non-interventional, multi-centre, German cohort study on leuprorelin in routine clinical practice. OBJECTIVES: To extend knowledge on the use, effectiveness, and tolerability of HEXAL/Sandoz leuprorelin (in this article, the term Leuprone® HEXAL® covers Leuprorelin Sandoz® as well) solid implant in patients with prostate cancer (PCa) in a real-world setting. METHODS: 959 PCa patients scheduled for androgen deprivation therapy (ADT) received leuprorelin acetate implant. Metabolism, serum prostate-specific antigen (PSA), and testosterone data, if available, were collected at baseline and follow-up visits for ≥12 months. RESULTS: Of 694 patients in the modified full analysis set, 26.4% received GnRH analogues ≤6 months before enrolment. Fifty-one percent of patients were treated for locally advanced or metastatic PCa. In 19.6% of patients, ADT was used in neoadjuvant or adjuvant settings and in 28.5% with rising PSA after definite therapy. Testosterone levels <0.5 ng/mL were achieved in >90% of patients. Safety profile was in line with the summary of product characteristics. Therapy was well tolerated, with patient-triggered therapy discontinuation in 3.6%. CONCLUSIONS: This interim analysis confirmed previous efficacy findings for leuprorelin implant in a real-world setting. This contemporary cohort showed a shift in the use of ADT to non-metastatic PCa stages.

Potential of an mRNA-Based Urine Assay (Xpert® Bladder Cancer Detection1) in Hematuria Patients - Results from a Cohort Study.

BACKGROUND AND OBJECTIVE: Assessment of patients with hematuria (aH) remains a challenge in urological practice, balancing the benefits of diagnosing a potentially underlying bladder cancer (UCa) against the risks of possibly unnecessary diagnostic interventions. This study analyzes the potential of an mRNA-based urine assay, the Xpert® Bladder Cancer Detection- CE-IVD (Xpert BC-D), in patients with hematuria. MATERIALS AND METHODS: Overall, 368 patients with newly observed painless hematuria and no history of UCa were included in this observational study. Patients received urological workup, including urethrocystoscopy (WLC), upper tract imaging, urine cytology and Xpert BC-D. Patients with positive WLC were recommended to undergo tumor resection (TUR-B). RESULTS: After excluding non-assessable cases, 324 patients were considered for analysis (188 males, 136 females; median age: 61 years). Eight of twenty-eight patients with a positive TUR-B had Ta low grade (LG) tumors; the others were diagnosed with high grade (HG) lesions (Ta: 4, CIS: 2, T1:11, > T1:3). The Xpert BC-D was more sensitive than urine cytology (96% vs. 61%) (p = 0.002). Increased risk ratios (RR) were observed for gross hematuria, gender, urine cytology, and positive Xpert BC-D (all p < 0.05). Age and positive Xpert BC-D remained independent predictors of UCa in multivariate analysis. Simulating a triage with WLC restricted to patients with positive Xpert BC-D could have saved 240 (74.1%) assessments at the cost of missing one pTa LG tumor. CONCLUSIONS: The results suggest a potential role for Xpert BC-D in preselecting patients with hematuria for either further invasive diagnosis or an alternate diagnostic procedure.

Simulation of the effects of molecular urine markers in follow-up of patients with high-risk non-muscle invasive bladder cancer.

A plethora of urine markers for the management of patients with bladder cancer has been developed and studied in the past. However, the clinical impact of urine testing on patient management remains obscure. The goal of this manuscript is to identify scenarios for the potential use of molecular urine markers in the follow-up of patients with high-risk non-muscle-invasive BC (NMIBC) and estimate potential risks and benefits. Information on the course of disease of patients with high-risk NMIBC and performance data of a point-of-care test (UBC rapid™), an MCM-5 directed ELISA (ADXBLADDER™), and 2 additional novel assays targeting alterations of mRNA expression and DNA methylation (Xpert bladder cancer monitor™, Epicheck™) were retrieved from high-quality trials and/or meta-analyses. In addition, the sensitivity of white light cystoscopy (WLC) and the impact of a urine marker result on the performance of WLC were estimated based on fluorescence cystoscopy data and information from the CeFub trial. This information was applied to different scenarios in patient follow-up and sensitivity, estimated number of cystoscopies, and the numbers needed to diagnose were calculated. The sensitivity of guideline-based regular follow-up (SOC) at 1 year was calculated at 96%. For different marker-supported strategies sensitivities ranging from 77% to 97.9% were estimated. Calculations suggest that several strategies are effective for the SOC. While for the SOC 24.6 WLCs were required to diagnose 1 tumor recurrence (NND), this NND dropped below 5 in some marker-supported strategies. Based on the results of this simulation, a marker-supported follow-up of patients with HR NMIBC is safe and offers the option to significantly reduce the number of WLCs. Further research focusing on prospective randomized trials is needed to finally find a way to implement urine markers into clinical decision-making.

Skeletal-related events in metastatic prostate cancer and the number needed to treat: a critical consideration.

PURPOSE: With stage migration induced by early diagnosis of prostate-specific antigen, the course of disease for prostate cancer (PCa) patients has changed. Increasingly, patients undergo long-term androgen ablation with consecutive risks including osteoporosis and pathologic fractures. A recent randomized trial found that the RANK ligand inhibitor denosumab was more effective preventing skeletal-related events in patients with metastatic PCa as compared to treatment with the bisphosphonate zoledronic acid. This improved efficacy was linked to an increase of side effects. METHODS: The present analysis compares results reported for both substances using a number needed to treat analysis approach. Based upon these findings, risk-benefit calculations were performed. RESULTS: The results demonstrate that for patients with bone metastatic castration-resistant PCa, decision for or against treatment with either denosumab or zoledronic acid must not only consider efficacy but needs to balance the desired effects versus potential side effects. This is of specific relevance since life expectancy is limited in this patient cohort with end-stage disease. CONCLUSIONS: Further scientific efforts are necessary to identify optimal dosing and application intervals for denosumab and zoledronic acid as well as to answer the question of optimal duration of treatment. These findings will directly impact the risk versus benefit relations for both therapeutic options.

Considering the Effects of Modern Point-of-Care Urine Biomarker Assays in Follow-Up of Patients with High-Risk Non-muscle-Invasive Bladder Cancer.

BACKGROUND: Although a plethora of urine markers for diagnosis and follow-up of patients with bladder cancer (BC) has been developed and studied, the clinical impact of urine testing on patient management remains unclear. The goal of this manuscript is to identify scenarios for a potential use of modern point-of-care (POC) urine marker assays in the follow-up of patients with high-risk non-muscle-invasive BC (NMIBC) and estimate potential risks and benefits. METHODS: To permit comparison between different assays, the results of 5 different POC assays studied in a recent prospective multicenter study including 127 patients with suspicious cystoscopy undergoing TURB were used for this simulation. For the current standard of care (SOC), a "marker-enforced" procedure, and a combined strategy sensitivity (Se), estimated number of cystoscopies, and the numbers needed to diagnose (NND) over a 1-year follow-up period were calculated. RESULTS: For regular cystoscopy (SOC), a Se of 91.7% and a NND of 42.2 repetitive office cystoscopies (WLCs) for 1 recurrent tumor at 1 year were calculated. For the "marker-enforced" strategy, marker sensitivities between 94.7% and 97.1% were observed. The "combined" strategy yielded for markers with a Se exceeding 50% an overall Se at 1 year similar or superior to the current SOC. Savings regarding the number of cystoscopies in the "marker-enforced" strategy vs. the SOC were small, while, depending on the marker, up to 45% of all cystoscopies may be saved using the "combined" strategy. CONCLUSIONS: Based on the results of this simulation, a marker-supported follow-up of patients with high-risk (HR) NMIBC is safe and offers options to significantly reduce the number of cystoscopies without compromising the Se. Further research focusing on prospective randomized trials is needed to finally find a way to include marker results into clinical decision-making.

Eosinophilic cystitis mimicking bladder cancer-considerations on the management based upon a case report and a review of the literature.

The hypereosinophilic syndrome (HES) is a rare disorder characterized by hypereosinophilia and infiltration of various organs with eosinophils. Eosinophilic cystitis (EC), mimicking bladder cancer clinically but also in ultrasound and in radiographic imaging, is one potential manifestation of the HES occurring in adults as well as in children. This case report describes the course of disease in a 57-year-old male presenting with severe gait disorders and symptoms of a low compliance bladder caused by a large retropubic tumor. After extensive urine and serologic examination and histologic confirmation of EC the patient was subjected to medical treatment with cetirizine and prednisolone for 5 weeks. While gait disorders rapidly resolved, micturition normalized only 10 months after initiation of therapy. Based upon this course the authors recommend patience and reluctance concerning radical surgical intervention in EC. Key Points • Eosinophilic cystitis is a rare condition with app. 200 cases reported, so far. • Etiology of eosinophilic cystitis is obscure, but allergies and parasitic infections may trigger the disease. • Genetic alterations (e.g., BRAF mutations) may predispose for the disease • Corticosteroids and antihistamines are the backbone of therapy and may be complemented by antibiotics and non-steroidal anti-inflammatory drugs in case of concomitant (underlying) infections. • As recovery can occur even after a long time, radical surgery should be restricted to highly selected cases.

Immunocytology in the assessment of patients with painless gross haematuria.

OBJECTIVE: To evaluate, in a prospective study, the role of immunocytology in assessing patients with gross haematuria. Due to the high prevalence of urothelial cancer in this population, a thorough assessment is mandatory to identify all patients with tumours. PATIENTS AND METHODS: We used Ucyt (DiagnoCure Inc., Quebec, Canada), a commercially available immunocytological assay based on the microscopic detection of tumour-associated antigens on the membrane of urothelial cells by immunofluorescence. Between October 2000 and March 2007, 61 consecutive patients with a first episode of painless gross haematuria, but no previous transitional cell carcinoma, were included. Urine samples were obtained from all patients and examined cytologically and immunocytologically. RESULTS: Clinically (by physical examination, laboratory tests, endoscopy and imaging) there was bladder cancer in 17 patients (28%); further diagnoses were benign prostatic enlargement (20, 33%), urinary tract infection (seven, 12%), urolithiasis (two, 3%), and 'further conditions' (seven, 12%). In 10 patients (16%) the reasons for haematuria were not disclosed. Of the 61 samples, 59 (97%) were assessable by cytology and immunocytology. For cystoscopy, immunocytology and conventional urine cytology the sensitivity was 76%, 88% and 47%, and the specificity 100%, 77% and 95%, respectively. Two bladder tumours were not detected by cystoscopy and immunocytology (one each), and two upper urinary tract tumours were diagnosed by imaging and immunocytology. CONCLUSIONS: The combination of cystoscopy and immunocytology gave 100% sensitivity, while combining cystoscopy and cytology only marginally improved the sensitivity of cystoscopy alone. As sensitivity appears to be of key relevance in assessing patients with gross haematuria, we suggest adding immunocytology to the diagnostic protocol in this situation.

Immunocytology in the assessment of patients with asymptomatic microhaematuria.

INTRODUCTION: Discrimination between malignant and nonmalignant conditions remains the key problem in assessing microhaematuria. This prospective study investigated the role of immunocytology in the evaluation of patients with microhaematuria. METHODS: uCyt+ is a commercially available immunocytologic assay based on microscopic detection of tumour-associated antigens on the membrane of urothelial cells by immunofluorescence. Between October 2000 and August 2005, 189 consecutive patients with newly diagnosed painless microhaematuria without prior transitional cell carcinoma were included. All urine samples were examined cytologically and immunocytologically. Of the 189 samples, 178 (94%) were assessable. RESULTS: Clinical assessment by physical examination, laboratory tests, endoscopy, and imaging modalities found bladder cancer in 8 patients (4%). Further diagnoses were benign prostatic hyperplasia (54 cases, 29%), cystitis (including interstitial cystitis; 20 cases, 11%), urolithiasis (18 cases, 9%), tumours of other origin (6 cases, 2%), and "further conditions" (26 cases, 13%). In 57 patients (30%) the reasons for haematuria were not disclosed. Immunocytology was positive in 7 of 8 bladder tumours (87%) and negative in 154 of 170 patients with haematuria for other reasons (91%). CONCLUSIONS: The high sensitivity and good specificity of immunocytology in the diagnosis of bladder cancer was confirmed in this population with a low disease prevalence. Only one tumour of low malignant potential was missed by immunocytology. If assessment of these patients would have been based only on immunocytology, 154 costly and invasive diagnostic procedures could have been avoided, with only 16 of 170 individuals (9%) undergoing these examinations unnecessarily. The findings justify a prospective investigation of this issue.