Validation of an mRNA-based Urine Test for the Detection of Bladder Cancer in Patients with Haematuria.

BACKGROUND: In patients with haematuria, a fast, noninvasive test with high sensitivity (SN) and negative predictive value (NPV), which is able to detect or exclude bladder cancer (BC), is needed. A newly developed urine assay, Xpert Bladder Cancer Detection (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC. OBJECTIVE: To validate the performance of Xpert in patients with haematuria. DESIGN, SETTING, AND PARTICIPANTS: Voided precystoscopy urine specimens were prospectively collected at 22 sites from patients without prior BC undergoing cystoscopy for haematuria. Xpert, cytology, and UroVysion procedures were performed. Technical validation was performed and specificity (SP) was determined in patients without BC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion. RESULTS AND LIMITATIONS: We included 828 patients (mean age 64.5 yr, 467 males, 401 never smoked). Xpert had an SN of 78% (95% confidence interval [CI]: 66-87) overall and 90% (95% CI: 76-96) for high-grade (HG) tumours. The NPV was 98% (95% CI: 97-99) overall. The SP was 84% (95% CI: 81-86). In patients with microhaematuria, only one HG patient was missed (NPV 99%). Xpert had higher SN and NPV than cytology and UroVysion. Cytology had the highest SP (97%). In a separate SP study, Xpert had an SP of 89% in patients with benign prostate hypertrophy and 92% in prostate cancer patients. CONCLUSIONS: Xpert is an easy-to-use, noninvasive test with improved SN and NPV compared with cytology and UroVysion, representing a promising tool for identifying haematuric patients with a low likelihood of BC who might not need to undergo cystoscopy. PATIENT SUMMARY: Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help identify (micro)haematuria patients with a very low likelihood to have bladder cancer.

Prospective Validation of an mRNA-based Urine Test for Surveillance of Patients with Bladder Cancer.

BACKGROUND: A fast, noninvasive test with high sensitivity (SN) and a negative predictive value (NPV), which is able to detect recurrences in bladder cancer (BC) patients, is needed. A newly developed urine assay, Xpert Bladder Cancer Monitor (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC. OBJECTIVE: To validate Xpert characteristics in patients previously diagnosed with non-muscle-invasive BC. DESIGN, SETTING, AND PARTICIPANTS: Voided precystoscopy urine samples were prospectively collected at 22 sites. Xpert, cytology, and UroVysion were performed. If cystoscopy was suspicious for BC, a histologic examination was performed. Additionally, technical validation was performed and specificity was determined in patients without a history or clinical evidence of BC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion. RESULTS AND LIMITATIONS: Of the eligible patients, 239 with a history of BC had results for all assays. The mean age was 71 yr; 190 patients were male, 53 never smoked, and 64% had previous intravesical immunotherapy (35%) or chemotherapy (29%). Forty-three cases of recurrences occurred. Xpert had overall SN of 74% (95% confidence interval [CI]: 60-85) and 83% (95% CI: 64-93) for high-grade (HG) tumors. The NPV was 93% (95% CI: 89-96) overall and 98% (95% CI: 94-99) for HG tumors. Specificity was 80% (95% CI: 73-85). Xpert SN and NPV were superior to those of cytology and UroVysion. Specificity in non-BC individuals (n=508) was 95% (95% CI: 93-97). CONCLUSIONS: Xpert has an improved NPV compared with UroVysion and cytology in patients under follow-up for BC. It represents a promising tool for excluding BC in these patients, reducing the need for cystoscopy. PATIENT SUMMARY: Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help optimize the follow-up of recurrent bladder cancer patients.

A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer.

BACKGROUND: The 4Kscore combines measurement of four kallikreins in blood with clinical information as a measure of the probability of significant (Gleason ≥7) prostate cancer (PCa) before prostate biopsy. OBJECTIVE: To perform the first prospective evaluation of the 4Kscore in predicting Gleason ≥7 PCa in the USA. DESIGN, SETTING, AND PARTICIPANTS: Prospective enrollment of 1012 men scheduled for prostate biopsy, regardless of prostate-specific antigen level or clinical findings, was conducted at 26 US urology centers between October 2013 and April 2014. INTERVENTION: The 4Kscore. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was Gleason ≥7 PCa on prostate biopsy. The area under the receiver operating characteristic curve, risk calibration, and decision curve analysis (DCA) were determined, along with comparisons of probability cutoffs for reducing the number of biopsies and their impact on delaying diagnosis. RESULTS AND LIMITATIONS: Gleason ≥7 PCa was found in 231 (23%) of the 1012 patients. The 4Kscore showed excellent calibration and demonstrated higher discrimination (AUC 0.82) and net benefit compared to a modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model and standard of care (biopsy for all men) according to DCA. A possible reduction of 30-58% in the number biopsies was identified with delayed diagnosis in only 1.3-4.7% of Gleason ≥7 PCa cases, depending on the threshold used for biopsy. Pathological assessment was performed according to the standard of care at each site without centralized review. CONCLUSION: The 4Kscore showed excellent diagnostic performance in detecting significant PCa. It is a useful tool in selecting men who have significant disease and are most likely to benefit from a prostate biopsy from men with no cancer or indolent cancer. PATIENT SUMMARY: The 4Kscore provides each patient with an accurate and personalized measure of the risk of Gleason ≥7 cancer to aid in decision-making regarding the need for prostate biopsy.

Rational antibiotic treatment of outpatient genitourinary infections in a changing environment.

In the outpatient setting, genitourinary infections (GUIs) remain costly to treat and are a significant cause of morbidity. Recent evidence supports more substantial roles for pathogens other than Escherichia coli, particularly gram-positive pathogens, in the pathogenesis of GUIs. Broad-spectrum agents should be considered in order to address this etiologic change appropriately. Criteria for antimicrobial selection set forth by the Council for Appropriate and Rational Antibiotic Therapy (CARAT) recommend using antibiotics that are supported by strong clinical evidence, have good susceptibility profiles, are safe, are cost-effective, and are used for the optimal duration. Evidence-based guidelines recommend considering local E coli resistance rates to trimethoprim-sulfamethoxazole and using fluoroquinolones as second-line therapy when resistance is high. Fluoroquinolones are recommended for the treatment of pyelonephritis and prostatitis. Among the fluoroquinolones, levofloxacin and gatifloxacin offer coverage for the gram-negative and gram-positive pathogens, which may make them preferable in treating urinary tract infections empirically in such patient groups. For the treatment of bacterial prostatitis, only trimethoprim and the fluoroquinolones possess both the appropriate bactericidal activity and the ability to diffuse into the prostate. Levofloxacin shows particularly good penetration into prostatic tissue. Safety issues to consider include imbalances in intestinal microflora caused by antimicrobial agents that may lead to overgrowth of vancomycin-resistant enterococci and Clostridium difficile-associated diarrhea. Once the optimal agent is identified, the optimal duration of treatment should be determined to maximize treatment success while minimizing the potential for resistance. Finally, cost considerations include the costs of treatment failure due to inappropriate therapy or nonadherence to the therapeutic regimen.

Multicenter initial U.S. experience with CoreTherm-monitored feedback transurethral microwave thermotherapy for individualized treatment of patients with symptomatic benign prostatic hyperplasia.

PURPOSE: To report the initial experience with CoreTherm-monitored transurethral microwave thermotherapy (TUMT) for individualized treatment of benign prostatic hyperplasia. PATIENTS AND METHODS: The CoreTherm procedure uses a urethral microwave catheter through which a tiny temperature sensor is placed in the adenoma to allow real-time monitoring of intraprostatic temperature during TUMT. The cell kill volume can be calculated and the treatment time adjusted to both the patient's actual prostate volume and the prostatic blood flow. A series of 102 patients was treated. RESULTS: All patients were able to tolerate the treatment in an outpatient clinic setting, with temperatures >49 degrees C being reached in all cases. The total treatment times averaged 25 minutes, and the peak intraprostatic temperature averaged 61 degrees C. The median catheter time was 8.5 days. Patients were followed an average of 5.6 months. The American Urological Association Scores fell to 11 from 18 prior to CoreTherm TUMT. There were minimal treatment-related complications. CONCLUSION: CoreTherm-monitored TUMT is safe and tolerable, with shorter treatments than are required by older forms of TUMT.