Prospective evaluation of the RT-PCR based urinary marker Bladder Epicheck® as a diagnostic tool in upper urinary tract tumor.

BACKGROUND: Upper-tract-urothelial-carcinoma (UTUC) represents 5-10% of all urothelial-neoplasms with increasing incidence in the last decades. Current standard tools for diagnosis of UTUC include cytology, computed tomography (CT) urography and ureterorenoscopy (URS). The aim of this study was to evaluate the impact of Bladder Epicheck® Test as diagnostic tool for UTUC diagnosis and recurrence. METHODS: Overall, 136 urine samples, selective collected from upper-urinary-tract before URS for suspicion of UTUC were analyzed with cytology and Bladder Epicheck® Test. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of both markers were calculated and compared to URS and/or histology as reference. RESULTS: UTUC was detected in 40 cases (33.3%), among them 30 were classified as low-grade (LG) and 10 as high-grade (HG). Overall sensitivity of Bladder Epicheck® for UTUC detection was 65% compared to 42.5% for cytology, increasing to 100% for Bladder Epicheck® and 90% for cytology if considering only HG tumors. Overall specificity of Bladder Epicheck® was 81.2% and of cytology 93.7%. PPV and NPV were 63.4% and 82.2% for Bladder Epicheck® and 77.2% and 76.5% for cytology. Considering an EpiScore cut-off >75, instead of 60, specificity of Bladder Epicheck® improves to 89% and PPV to 74.2%. Limitations include the use of a marker validated only for bladder-cancer and the relatively small number of cases. CONCLUSIONS: Due to its high sensitivity for HG tumors, the Bladder Epicheck® Test can be used in diagnosis and treatment decision-making of UTUC. Furthermore, it could be very useful in follow-up of UTUC, after endoscopic treatment to postpone or avoid unnecessary endoscopic exploration. Even if further studies are needed to validate these findings, Bladder Epicheck® could be a promising clinical tool for detection of UTUC.

Extended Safety and Tolerability of Darolutamide for Nonmetastatic Castration-Resistant Prostate Cancer and Adverse Event Time Course in ARAMIS.

BACKGROUND: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are usually asymptomatic and seek treatments that improve survival but have a low risk of adverse events. Darolutamide, a structurally distinct androgen receptor inhibitor (ARi), significantly reduced the risk of metastasis and death versus placebo in ARAMIS. We assessed the extended safety and tolerability of darolutamide and the time-course profile of treatment-emergent adverse events (TEAEs) related to ARis and androgen-suppressive treatment. PATIENTS AND METHODS: Patients with nmCRPC were randomized 2:1 to darolutamide (n = 955) or placebo (n = 554). After trial unblinding, patients could receive open-label darolutamide. Tolerability and TEAEs were assessed every 16 weeks. Time interval-specific new and cumulative event rates were determined during the first 24 months of the double-blind period. RESULTS: Darolutamide remained well tolerated during the double-blind and open-label periods, with 98.8% of patients receiving the full planned dose. The incidence of TEAEs of interest in the darolutamide group was low and ≤2% different from that in the placebo group, except for fatigue. When incidences were adjusted for exposure time, there were minimal differences between the darolutamide double-blind and double-blind plus open-label periods. The rate of initial onset and cumulative incidence of grade 3/4 TEAEs and serious TEAEs were similar for darolutamide and placebo groups over 24 months. CONCLUSION: Extended treatment with darolutamide was well tolerated and no new safety signals were observed. Most ARi-associated and androgen-suppressive treatment-related TEAEs occurred at low incidences with darolutamide, were similar to placebo, and showed minimal increase over time with continued treatment. TRIAL NUMBER: ClinicalTrials.gov identifier NCT02200614.

Safety and tolerability of long-term treatment with darolutamide in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: In patients with metastatic castration-resistant prostate cancer, darolutamide was well tolerated for 25 months, but minimal long-term safety data are available. METHODS: Treatment-emergent adverse events (TEAEs) for patients receiving darolutamide for a median of 38 months (n = 13) are described in this pooled analysis of individual patient data from phase 1/2 studies. RESULTS: All patients reported TEAEs (mostly grade 1/2). The most common TEAEs were diarrhea, abdominal pain, and nausea. Serious TEAEs were reported in six patients (none related to darolutamide). All treatment-related TEAEs (n = 5) were grade 1. CONCLUSIONS: Long-term darolutamide treatment was well tolerated; no new safety signals observed. In patients with mCRPC, long-term darolutamide treatment was well tolerated and no new safety signals were observed. These findings are consistent with previous reports, demonstrating a favorable safety and tolerability profile of darolutamide.

Efficacy and safety outcomes of darolutamide in patients with non-metastatic castration-resistant prostate cancer with comorbidities and concomitant medications from the randomised phase 3 ARAMIS trial.

PURPOSE: In patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the Androgen Receptor Antagonizing Agent for Metastasis-free Survival (ARAMIS) trial, darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable safety/tolerability profile. This post hoc analysis of ARAMIS evaluated efficacy and safety in patients by number of comorbidities and concomitant medications. METHODS: Patients with nmCRPC were randomised 2:1 to darolutamide (n = 955) or placebo (n = 554) while continuing androgen-deprivation therapy. Overall survival (OS) and treatment-emergent adverse events (TEAEs) were evaluated in subgroups by median numbers of ongoing comorbidities and concomitant medications. HRs were determined from univariate analysis using Cox regression. FINDINGS: Median numbers of comorbidities and concomitant medications were 6 and 10, respectively, with 41.6% of patients having >6 comorbidities and 48.8% taking >10 concomitant medications. For patients with ≤ 6 and >6 comorbidities, darolutamide increased OS versus placebo (hazard ratio [HR] 0.65 and 0.73, respectively), and this benefit was consistent for cardiovascular, metabolic, and other comorbidities (HR range: 0.39-0.88). For patients taking ≤ 10 and >10 concomitant medications, increased OS was also observed with darolutamide versus placebo (HR 0.76 and 0.66, respectively), and the benefit was consistent across medication classes (HR range: 0.45-0.80). Incidences of TEAEs and TEAEs leading to treatment discontinuation with darolutamide were similar to placebo across subgroups by numbers of comorbidities and concomitant medications. CONCLUSIONS: The OS benefit and safety of darolutamide remained consistent with that observed in the overall ARAMIS population, even in patients with high numbers of comorbidities or concomitant medications. GOV REGISTRATION: NCT02200614. TWEETABLE ABSTRACT: Darolutamide increased overall survival versus placebo, and incidences of most adverse events were similar between treatments in patients with ≤ 6 or >6 comorbidities and those taking ≤ 10 or >10 concomitant medications.

A randomised, double-blind, dose-finding, phase II multicentre study of ODX in the treatment of patients with castration-resistant prostate cancer and skeletal metastases.

AIMS: This study aimed to assess the efficacy and safety of ODX, a novel, cytotoxic, bone-targeting drug candidate, in castration-resistant prostate cancer bone metastatic disease. METHODS: Patients with progressive disease were randomised to ten cycles of ODX, intravenous infusion Q2W (3, 6, and 9 mg/kg, respectively). The primary objective was to assess the relative change from baseline in bone alkaline phosphatase (B-ALP) and serum-aminoterminal-propeptide of Type I procollagen (S-P1NP) at 12 weeks. The inclusion criteria selected were broad, and a double-blind design was used to ensure objective recruitment of patients for the assessment of efficacy. None of the patients received bone-protecting agents during the ODX treatment period. RESULTS: Fifty-five 21,20 and 14) patients were randomised to ODX (3, 6 and 9 mg/kg), respectively. The lower number of patients in arm 3 was due to too low a recruitment rate towards the end of the study. The median treatment time were 14, 13 and 14 weeks, respectively. The decrease in B-ALP at 12 weeks in study arms 3, 6 and 9 mg/kg was seen in 6/15 (40%), 8/12 (67%) and 5/12 (42%) patients, respectively, whereas the corresponding numbers for P1NP were 8/15 (53%), 8/12 (67%), and 4/12 (33%), respectively. The median decrease in B-ALP and P1NP at 12 weeks for study arms 3, 6 and 9 mg/kg were 37%, 14% and 43%, respectively, and 51%, 40% and 64%, respectively. The decrease in serum C-terminal telopeptide at 12 weeks was seen in the vast majority of patients and in about one-third of patients in bone scan index. ODX was well tolerated, and no drug-related serious adverse events occurred. There were no significant differences between study arms regarding efficacy and safety. CONCLUSIONS: ODX was well tolerated and demonstrated inhibitory effects on markers related to the vicious cycle in bone at all three doses. The reduction in metastatic burden, assessed with bone scan index, supports this finding. Studies with continued ODX treatment until disease progression are being planned (ClinicalTrials.gov Identifier: NCT02825628).

Efficacy and Safety of Darolutamide in Patients with Nonmetastatic Castration-resistant Prostate Cancer Stratified by Prostate-specific Antigen Doubling Time: Planned Subgroup Analysis of the Phase 3 ARAMIS Trial.

BACKGROUND: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific antigen doubling time (PSADT) is ≤6 mo. However, patients remain at a high risk with a PSADT of >6 mo. OBJECTIVE: To evaluate the efficacy and safety of darolutamide versus placebo in patients stratified by PSADT >6 or ≤6 mo. DESIGN, SETTING, AND PARTICIPANTS: A planned subgroup analysis of a global multicenter, double-blind, randomized, phase 3 trial in men with nmCRPC and PSADT ≤10 mo was conducted. INTERVENTION: Patients were randomized 2:1 to oral darolutamide 600 mg twice daily or placebo, while continuing androgen-deprivation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was metastasis-free survival (MFS). Secondary endpoints were overall survival (OS) and times to pain progression, first cytotoxic chemotherapy, and symptomatic skeletal events. Quality of life (QoL) was measured using validated prostate-relevant tools. Safety was recorded throughout the study. RESULTS AND LIMITATIONS: Of 1509 patients enrolled, 469 had PSADT >6 mo (darolutamide n = 286; placebo n = 183) and 1040 had PSADT ≤6 mo (darolutamide n = 669; placebo n = 371). Baseline characteristics were balanced between subgroups. Darolutamide significantly prolonged MFS versus placebo in both subgroups (unstratified hazard ratio [95% confidence interval]: PSADT >6 mo, 0.38 [0.26-0.55]; PSADT ≤6 mo, 0.41 [0.33-0.52]). OS and other efficacy and QoL endpoints favored darolutamide with significant improvement over placebo in both subgroups. The incidence of adverse events, including events commonly associated with androgen receptor inhibitors (fractures, falls, hypertension, and mental impairment), and discontinuations due to adverse events were low and similar to placebo. Limitations include small subgroup populations. CONCLUSIONS: In patients with nmCRPC and PSADT >6 mo (maximum 10 mo), darolutamide provided a favorable benefit/risk ratio, characterized by significant improvements in MFS, OS, and other clinically relevant endpoints; maintenance of QoL; and favorable tolerability. PATIENT SUMMARY: In patients with prostate cancer that has stopped responding to standard hormonal therapy (indicated by an increase in prostate-specific antigen [PSA] levels), there is a risk that the cancer will spread to other parts of the body. This risk is highest when the time it takes for the PSA level to double (ie, "PSA doubling time" [PSADT]) is less than 6 mo. However, there is still a risk that the cancer will spread even if the PSADT is longer than 6 mo. In a group of patients whose PSADT was more than 6 mo but no more than 10 mo, treatment with darolutamide slowed the cancer spread and allowed them to live longer than patients who received placebo (inactive drug). Darolutamide treatment did not cause many side effects and helped maintain patients' quality of life without disruptions.

Recurrent Prostate Cancer Diagnostics with 18F-PSMA-1007 PET/CT: A Systematic Review of the Current State.

BACKGROUND: Early diagnosis of recurrent prostate cancer is a cornerstone for further adequate therapy planning. Therefore, clinical practice and research still focuses on diagnostic tools that can detect prostate cancer in early recurrence when it is undetectable in conventional diagnostic imaging. 18F-PSMA-1007 PET/CT is a novel method to evaluate patients with biochemical recurrent PCa. The aim of this review was to evaluate the role of 18F-PSMA-1007 PET/CT in prostate cancer local recurrence, lymph node metastases and bone metastases detection. METHODS: Original studies, reviews and five meta-analyses were included in this article. A total of 70 studies were retrieved, 31 were included in the study. RESULTS: All patients described in the studies underwent 18F-PSMA-1007 PET/CT. The administered 18F-PSMA-1007 individual dose ranged from 159 ± 31 MBq to 363.93 ± 69.40 MBq. Results showed that 18F-PSMA-1007 PET/CT demonstrates a good detection rate in recurrent prostate cancer. CONCLUSIONS: 18F-PSMA-1007 PET/CT appears to achieve reliable performance in detecting recurrent prostate cancer. The high detection rate of 18F-PSMA-1007 PET/CT in recurrent prostate cancer was confirmed, especially in local recurrence and small lymph nodes with non-specific characteristics on conventional diagnostic imaging methods. However, several authors emphasize some limitations for this tracer-for example, non-specific uptake in bone lesions that can mimic bone metastases.

Diagnostic scope of 18F-PSMA-1007 PET/CT: comparison with multiparametric MRI and bone scintigraphy for the assessment of early prostate cancer recurrence.

The aim of this study was to compare the diagnostic tools-18F-PSMA-1007 positron emission tomography (PET/CT), magnetic resonance imaging (MRI) and bone scintigraphy for the evaluation of local recurrence, regional lymph nodes and bone metastases of recurrent prostate cancer (PCa). 28 PCa patients after radical prostatectomy and/or radiation therapy and with biochemical relapse were enrolled in this study. The evaluation of local recurrence and regional lymph node metastases was based on results of PET/CT and MRI. Local recurrent disease in 28 patients was detected by PET/CT in 36% (10/28) and by MRI in 32% (9/28) with sensitivity, specificity, accuracy of 90.9%, 100%, 96.4% and 81.8%, 100%, 92.9%, respectively (kappa 0.92, P<0.001). Nodal involvement was confirmed by PET/CT and MRI in 46% (13/28) and 25% (7/28) with sensitivity, specificity and accuracy for PET/CT 92.3%, 93.3%, 92.9% and for MRI-53.8%, 100%, 78.6%, respectively (kappa 0.57, P<0.001). The evaluation of skeletal metastases was based on PET/CT and bone scintigraphy. Bone metastases were seen on PET/CT and bone scintigraphy in 21% (6/28) and 20% (5/25) with sensitivity, specificity and accuracy of 100%; 91.7%; 92.9% and 50.0%; 85.7%; 80.0%, respectively (kappa 0.41, P<0.01). In conclusion, our comparative study demonstrates advantages of 18F-PSMA-1007 PET/CT compared to MRI and scintigraphy for the evaluation of recurrent prostate cancer. Both methods, 18F-PSMA-1007 PET/CT and MRI, detect local recurrence with high accuracy and excellent agreement, which may be attributed to the low urinary background clearance of 18F-PSMA-1007.

Darolutamide and health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: An analysis of the phase III ARAMIS trial.

BACKGROUND: In the ARAMIS trial, darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT significantly improved metastasis-free survival (MFS), overall survival (OS) and time to pain progression in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Herein, we present analyses of patient-reported health-related quality of life (HRQoL) outcomes. PATIENTS AND METHODS: This double-blind, placebo-controlled, phase III trial randomised patients with nmCRPC and prostate-specific antigen doubling time ≤10 months to darolutamide 600 mg (n = 955) twice daily or matched placebo (n = 554) while continuing ADT. The primary end-point was MFS; the secondary end-points included OS and time to pain progression. In this analysis, HRQoL was assessed by the time to deterioration using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) prostate cancer subscale (PCS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module (EORTC QLQ-PR25) subscales. RESULTS: Darolutamide significantly prolonged time to deterioration of FACT-P PCS versus placebo (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.70-0.91; P = 0.0005) at the primary analysis (cut-off date: 3rd September 2018). Time to deterioration of EORTC QLQ-PR25 outcomes showed statistically significant delays with darolutamide versus placebo for urinary (HR 0.64, 95% CI 0.54-0.76; P < 0.0001) and bowel (HR 0.78, 95% CI 0.66-0.92; P = 0.0027) symptoms. Time to worsening of hormonal treatment-related symptoms was similar between the two groups. CONCLUSION: In patients with nmCRPC who are generally asymptomatic, darolutamide maintained HRQoL by significantly delaying time to deterioration of prostate cancer-specific quality of life and disease-related symptoms versus placebo.

Bladder cancer trends in Latvia during 1990-2017: incidence, mortality, and survival rates.

INTRODUCTION: The aim of this article was to evaluate bladder cancer (BC) incidence, mortality and survival trends in Latvia over the past 28 years. MATERIAL AND METHODS: Our study included patients diagnosed with BC between 1990 and 2017. The data were obtained from the national population-based cancer registry. Joinpoint regression analysis was used to identify points where a significant change in incidence and mortality trends occurred, accordingly with the patient's gender and age. Relative survival (RS) was estimated by Ederer I and II methods. RESULTS: Altogether, 9589 patients with initial BC diagnosis were included in the study. The age-standardised (ASR) incidence rates (per 100,000) increased from 6.8 in 1990 to 12.5 in 2014 followed by a statistically insignificant decrease continuing up to 2017. The ASR BC mortality rates (per 100,000) also rose from 3.9 in 1990 to 4.4 in 2017. However, there was a decline in BC mortality trends in the age-group 40-59 with annual percentage change (APC) -1.1%. RS rates increased from 55.0 % in 1990-2000 to 59.0% in years 2013-2017. CONCLUSIONS: This study revealed that the incidence and mortality rates have been gradually increasing over the past 28 years. The exception being cancer-specific mortality in the age group 40-59, which tends to decrease. Although the 5-year RS rates improved over the reviewed period, there is still plenty of room for improvement.

Diagnostic value of Xpert® Bladder Cancer Monitor in the follow-up of patients affected by non-muscle invasive bladder cancer: an update.

AIMS: Xpert® Bladder Cancer Monitor is a urinary marker based on the evaluation of five target mRNAs overexpressed in patients with bladder cancer (BC). The aim of our study is to update our results regarding the diagnostic accuracy of the Xpert® Bladder Cancer Monitor test in the follow-up of patients with non-muscle invasive bladder cancer (NMIBC). METHODS: We conducted a prospective study on 1015 samples of 416 patients (mean age 72.2 ± 10.3 years) under follow-up for NMIBC. Patients underwent voided urinary cytology, the Xpert® Bladder Cancer Monitor test and cystoscopy and, if positive, a transurethral resection of the bladder. Xpert® Bladder Cancer Monitor was reported as negative or positive: cut-off total Linear Discriminant Analysis (LDA) = 0.5. RESULTS: We identified 168 recurrent tumours: 126 (75%) were low-grade (LG) and 42 (25%) high-grade (HG). Overall sensitivity was 17.9% for cytology, 52.4% for Xpert® Bladder Cancer Monitor and 54.2% for the two tests combined. The sensitivity of cytology increased from 6.3% in LG to 52.4% in HG tumours whereas Xpert® Bladder Cancer Monitor showed a sensitivity ranging from 42.9% in LG to 80.9% in HG tumours. Combined cytology and Xpert® Bladder Cancer Monitor yielded an overall sensitivity of 45.2% for LG and 80.9% for HG tumours. Overall specificity was 98.5% for cytology and 78.4% for Xpert® Bladder Cancer Monitor and 78.2% for the two tests combined. The area under the curve (AUC) for Xpert® Bladder Cancer Monitor was 0.71; stratifying the patients according to the European Association of Urology risk groups, the AUC was 0.69, 0.67 and 0.85 for low, intermediate and high risk, respectively (p = 0.0003). CONCLUSION: Our data confirm a significantly higher sensitivity of Xpert® Bladder Cancer Monitor than for cytology in a larger patient cohort. The test performed very well in terms of specificity but could not reach the high value of cytology. Along with voided urinary cytology the test could allow to reduce cystoscopies in follow-up patients, reducing discomfort to the patients and costs.

Can conventional urodynamic variables help to predict the necessity of overactive bladder symptomatic therapy in women after transobturator tape surgery?

INTRODUCTION: The aim of this study was to find out if there are any conventional urodynamic (UDS) variables that would help to predict the necessity of overactive bladder (OAB) symptomatic therapy in women after transobturator tape surgery (TOT). MATERIAL AND METHODS: A total of 487 females after TOT were enrolled in this retrospective study. Inclusion criteria (UDS before surgery, follow-up visit within 2-6 month after TOT) were met in 169 women. Based on patient history, questionnaires and physical examination, two groups were distinguished: pure stress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (MixUI). A statistical analysis was performed including age and UDS variables. T-test was used for continuous data and Chi-squared test for categorical data. Combinations of these factors were analyzed using binary logistic regression and surgery outcome as the target variable. RESULTS: Significant correlations between the probability of a need for OAB therapy after TOT were observed with age (higher age increases OAB therapy necessity, p <0.001) and such UDS variables as cystometric capacity (CC) p <0.001; maximum flow rate (Qmax) p <0.001; detrusor contractility index (DCI) p <0.015 - higher value decreased the need for OAB therapy. Critical limit for these values: 60 years for age, 300 ml for CC, 15 ml/s for Qmax, but no specific value for DCI was observed. Binary logistic regression showed that the UI Group (p <0.01) and CC (p = 0.01) allow correctly classify 78.9% of TOT outcome (increased CC and SUI group are factors for TOT normal outcome). CONCLUSIONS: UI group, age, CC, Qmax, DCI can help to predict the necessity of OAB symptomatic therapy in women after TOT.

Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide.

BACKGROUND: Darolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. In the planned primary analysis of a phase 3 trial, the median metastasis-free survival was significantly longer with darolutamide (40.4 months) than with placebo (18.4 months). The data for the analysis of overall survival were immature at the time of the primary analysis. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 1509 men, in a 2:1 ratio, to receive darolutamide (955 patients) or placebo (554 patients) while they continued to receive androgen-deprivation therapy. After the results of the primary end-point analysis were found to be positive, unblinding of the treatment assignments occurred, and patients in the placebo group were permitted to cross over to receive open-label darolutamide treatment. At the time of this prespecified final analysis, which had been planned to be performed after approximately 240 deaths had occurred, overall survival and all other secondary end points were evaluated. RESULTS: The median follow-up time was 29.0 months. At the time of unblinding of the data, all 170 patients who were still receiving placebo crossed over to receive darolutamide; 137 patients who had discontinued placebo before unblinding had occurred received at least one other life-prolonging therapy. Overall survival at 3 years was 83% (95% confidence interval [CI], 80 to 86) in the darolutamide group and 77% (95% CI, 72 to 81) in the placebo group. The risk of death was significantly lower, by 31%, in the darolutamide group than in the placebo group (hazard ratio for death, 0.69; 95% CI, 0.53 to 0.88; P = 0.003). Darolutamide was also associated with a significant benefit with respect to all other secondary end points, including the time to first symptomatic skeletal event and the time to first use of cytotoxic chemotherapy. The incidence of adverse events after the start of treatment was similar in the two groups; no new safety signals were observed. CONCLUSIONS: Among men with nonmetastatic, castration-resistant prostate cancer, the percentage of patients who were alive at 3 years was significantly higher among those who received darolutamide than among those who received placebo. The incidence of adverse events was similar in the two groups. (Funded by Bayer HealthCare and Orion Pharma; ARAMIS ClinicalTrials.gov number, NCT02200614.).

Accuracy of 68Ga-PSMA-11 PET/CT and multiparametric MRI for the detection of local tumor and lymph node metastases in early biochemical recurrence of prostate cancer.

Anatomical and functional imaging plays a decisive role for detection and staging, of prostate cancer both primarily and post-treatment. While multiparametric MRI offers anatomic imaging with excellent soft tissue contrast, hybrid imaging based on positron emission tomography in combination with computed tomography (PET/CT) contributes functional imaging capacities. Since 68Ga-PSMA-11 was expected to be more efficient than the prior Choline-based PET radiotracers, it was the aim of the study to evaluate the diagnostic performance of the 68Ga-PSMA-11 PET/CT and multiparametric MRI in patients with recurrent prostate cancer and low PSA levels. 32 out of a cohort of 128 prostate cancer patients with biochemical relapse were referred for 68Ga-PSMA-11 PET/CT, MRI and bone scintigraphy. According to the histopathologically or clinically defined reference standard all results were classified as true positive, false positive, true negative or false negative. Local recurrence was present in 11/32 patients, lymph node metastases - in 13/32 patients and, bone metastases - in 6/32 patients. Against the standard of reference, sensitivity, specificity and accuracy for local recurrence of PET/CT were 63.6 %; 73.7%; 77.8%, respectively. MRI reached 90.9%; 94.7%; 92.3%, respectively. For local lymph node metastases PET/CT - 83.3%; 80.0% and 90.6%, respectively. MRI - 41.7%; 94.4%; 72.0%, respectively. For evaluation of bone metastases in PET/CT - 83.3%; 92.0%; 71.0%, respectively. Bone scintigraphy - 50.0%; 84.0%; 77.4%, respectively. In conclusion, mpMRI offered the better diagnostic accuracy in the detection of local recurrence and while PSMA PET/CT was superior in the detection of distant and lymph node metastases.

The role of conventional urodynamic in diagnosing specific types of urinary incontinence in women.

OBJECTIVE: To analyze the association between patient history profile, conventional urodynamic variables, and specific types of urinary incontinence (UI) in order to establish the role of urodynamic in differentiating various types of UI in women. MATERIAL AND METHODS: This cross-sectional study enrolled 547 women with UI. All patients were divided into three groups according to the UI type based on questionnaires: stress UI (SUI), mixed UI (MixUI), and urgent UI (UUI). Patient history taking, physical examination, and conventional urodynamics were performed. The association between patient profile characteristics, urodynamic data, and type of UI were assessed using one-way analysis of variance and chi-square tests. RESULTS: Significant correlations were observed between the age, body mass index (BMI), cystocele, menopausal status, and most urodynamic data in at least one UI group (p<0.05). Age differed among all three groups (p<0.001), with SUI group consisting the youngest patients. BMI was higher in the MixUI group (p=0.001). The maximum cystometric capacity differed among all three groups (p<0.001), with the highest in the SUI. The maximum flow rate was higher in the SUI group than that in the UUI group (p<0.001). Residual urine, opening detrusor pressure, and pressure transmission ratio were significantly higher in the UUI group. Detrusor overactivity and menopause were less frequently observed in the SUI group. The least pronounced urodynamic SUI was found in the UUI group. Spearman correlation for cystocele was negative in the SUI and positive in the UUI group. CONCLUSION: Conventional urodynamics give additional information to correctly diagnose specific types of UI in women.

Comparison of 2 new real-time polymerase chain reaction-based urinary markers in the follow-up of patients with non-muscle-invasive bladder cancer.

BACKGROUND: The objective of the current study was to compare the diagnostic accuracy of 2 new real-time polymerase chain reaction-based urinary markers with each other and with urinary cytology, cystoscopy, and/or histology in patients being followed for non-muscle-invasive bladder cancer. METHODS: A total of 487 patients were enrolled in the study. Patients were evaluated using voided urine cytology, the Xpert Bladder Cancer Monitor, the Bladder EpiCheck test, and white light cystoscopy. RESULTS: The overall sensitivity was 27.17% for cytology, 64.13% for the Bladder EpiCheck test, and 66.3% for the Xpert Bladder Cancer Monitor. The overall specificity was 98.82% for cytology, 82.06% for the Bladder EpiCheck test, and 76.47% for the Xpert Bladder Cancer Monitor. The negative predictive value was very similar for the 3 tests at 83.56% for cytology, 89.42% for the Bladder EpiCheck test, and 89.35% for the Xpert Bladder Cancer Monitor. When combined, the Bladder EpiCheck test and Xpert Bladder Cancer Monitor detected overall 79.35% of the tumors: 70.37% in low-grade and 92.11% in high-grade tumors. CONCLUSIONS: The Xpert Bladder Cancer Monitor and Bladder EpiCheck test were found to perform very well in terms of sensitivity. Together, the 2 tests detected approximately 92.11% of high-grade tumors. Their specificity was high but could not reach the excellent value of cytology. The negative predictive value was the same for both tests and was higher than that for cytology, especially when the tests were used together (92.24%). These 2 new tests hold promise as urinary biomarkers. They may be used in combination to maximize sensitivity in a less invasive way, thereby reducing invasiveness in the follow-up of patients with non-muscle-invasive bladder cancer and decreasing discomfort for the patients as well as complications and costs.

ODM-204, a Novel Dual Inhibitor of CYP17A1 and Androgen Receptor: Early Results from Phase I Dose Escalation in Men with Castration-resistant Prostate Cancer.

BACKGROUND: Most prostate cancer patients develop castration-resistant prostate cancer (CRPC) after androgen deprivation therapy treatment. CRPC growth is mediated mostly by androgen receptor signalling driven by primary androgens synthesised largely by the CYP17A1 enzyme. OBJECTIVE: To evaluate the safety profile and dose-limiting toxicities of ODM-204. DESIGN, SETTING, AND PARTICIPANTS: In this open, uncontrolled, nonrandomised, multicentre, tolerability and pharmacokinetic first-in-man phase I dose escalation study, patients with metastatic CRPC were randomised to receive ODM-204 in sequential cohorts of five dose levels (ie, 50, 100, 200, 300, and 500mg twice daily) concomitantly with prednisone. INTERVENTION: ODM-204, a novel, orally administered, investigational, nonsteroidal dual inhibitor of CYP17A1 and androgen receptor. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: ODM-204 plasma concentrations, serum testosterone, and prostate-specific antigen (PSA) levels were evaluated and imaging of lesions was performed. RESULTS AND LIMITATIONS: Of the 23 patients enrolled into the study, 60.9% experienced mild adverse effects considered to be related to the study treatment, which were fatigue, increased/decreased appetite, nausea, asthenia, diarrhoea, and weight decrease. ODM-204 area under the curve (AUC0-12) values increased dose dependently until the 300mg dose. The AUC was lower on day 8 after repeated dosing compared with day 1 from the 200mg dose upwards. Decreases in testosterone levels were seen with ODM-204 treatment confirming androgen deprivation. Of the patients, 13% also demonstrated a >50% decrease in PSA at week 12 and continued ODM-204 treatment for over a year. CONCLUSIONS: ODM-204 was well tolerated up to the highest evaluated dose. There were decreases in both testosterone and PSA levels, suggesting preliminary antitumour activity in the treatment of CRPC. The pharmacokinetic properties of the molecule, however, prevent further development. PATIENT SUMMARY: This study looked at the safety of ODM-204, a novel dual inhibitor of CYP17A1 and the androgen receptor, in castration-resistant prostate cancer patients. ODM-204 treatment was found to be well tolerated, and it also reduced both serum testosterone and prostate-specific antigen levels, but the properties of the molecule prevent further development.

First-in-man Safety and Efficacy of the ClearRing Implant for the Treatment of Benign Prostatic Hyperplasia.

BACKGROUND: Although effective for benign prostatic hyperplasia (BPH), transurethral resection of the prostate (TURP) can be associated with side effects including prolonged recovery, storage and voiding symptoms, and a risk of acute urinary retention. OBJECTIVE: To test a new minimally invasive device for the treatment of lower urinary tract symptoms (LUTS) due to BPH, involving implantation of a C-shaped nitinol ring (ClearRing) in a circular incision in the prostatic tissue using an electrocuting blade over a dilatation balloon. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter single-arm clinical trial involving 29 men with severe symptomatic BPH. INTERVENTION: Implantation of a ClearRing device under regional anesthesia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Effectiveness in alleviating LUTS was assessed in terms of International Prostate Symptom Score (IPSS) at baseline and 3, 6, and 12 mo after the procedure. To evaluate changes from baseline, a general estimating equation model was fitted to IPSS, the Quality of Life (QOL) scale, Benign Prostatic Hyperplasia Impact Index, maximum flow rate (Qmax), and postvoid residual volume. Statistical significance was defined as p<0.05. RESULTS AND LIMITATIONS: The average age was 71.4 yr, prostate size was 35-50cm3, and IPSS was 21.6. All procedures were successfully completed with one implant in 28 patients and two implants in one patient. No serious complications occurred. Patients experienced symptom relief by 3 mo that was sustained to 12 mo. Mean IPSS, QOL, and Qmax improved by 45%, 41%, and 40% by 3 mo, and 53%, 52%, and 49% by 12 mo, respectively (p<0.05). Adverse events were mild and transient. There were no reports of loss of antegrade ejaculation or any effects on erectile function. Implantation positioning failed in 11/29 patients, who then underwent uneventful TURP. After modification of the delivery device, the success rate for implant positioning improved from 5/13 patients to 13/16 patients. Study limitations include the single-arm nature and the low patient number. CONCLUSIONS: We demonstrated preliminary feasibility of the ClearRing device for minimally invasive treatment of BPH in men. Further studies are needed to confirm the safety and efficacy of this approach. PATIENT SUMMARY: In this study we tested outcomes after implantation of a ClearRing device in patients with benign prostatic hyperplasia. We found that the device was safe and effective. However, there was a high rate of implantation failure due to malpositioning, which was significantly improved following modification of the delivery device.

Differential binding cell-SELEX method to identify cell-specific aptamers using high-throughput sequencing.

Aptamers have in recent years emerged as a viable alternative to antibodies. High-throughput sequencing (HTS) has revolutionized aptamer research by increasing the number of reads from a few (using Sanger sequencing) to millions (using an HTS approach). Despite the availability and advantages of HTS compared to Sanger sequencing, there are only 50 aptamer HTS sequencing samples available on public databases. HTS data in aptamer research are primarily used to compare sequence enrichment between subsequent selection cycles. This approach does not take full advantage of HTS because the enrichment of sequences during selection can be due to inefficient negative selection when using live cells. Here, we present a differential binding cell-SELEX (systematic evolution of ligands by exponential enrichment) workflow that adapts the FASTAptamer toolbox and bioinformatics tool edgeR, which are primarily used for functional genomics, to achieve more informative metrics about the selection process. We propose a fast and practical high-throughput aptamer identification method to be used with the cell-SELEX technique to increase the aptamer selection rate against live cells. The feasibility of our approach is demonstrated by performing aptamer selection against a clear cell renal cell carcinoma (ccRCC) RCC-MF cell line using the RC-124 cell line from healthy kidney tissue for negative selection.