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.

Replacing cystoscopy by urine markers in the follow-up of patients with low-risk non-muscle-invasive bladder cancer?-An International Bladder Cancer Network project.

RATIONALE: Numerous molecular urine markers for the diagnosis of bladder cancer have been developed and evaluated mostly in case-control settings through the past decades. However, despite all efforts none of them has been included into clinical decision-making and guideline recommendations until today. The aim of this retrospective longitudinal analysis was to investigate if a molecular marker might be able to replace cystoscopy as a primary examination in diagnosis and follow-up of patients with pTa grade 1-2 bladder cancer. MATERIALS AND METHODS: Totally 36 patients (32 men) with pTa grade 1-2 bladder cancer underwent 232 follow-up examinations including urine analysis, cytology, immunocytology (uCyt+), and urethrocystoscopy (UC). Mean age at study entry was 63 years. Patients were observed through a median follow-up interval of 3.8 years. RESULTS: In summary, 47 Transurethral Resection of Bladder Tumors (TURB) procedures were indicated based upon a positive UC (44) or as re-TURB (3) and 33 tumors (plus 1 case of pTa G0) were histopathologically confirmed. Although uCyt+was positive in 12/13 primary tumors (92.3%), sensitivity dropped to 13/20 (65%) in tumor recurrence presumably because of their smaller size. Urine cytology had a sensitivity and a specificity of 30.3% and 94.9%, respectively, but did not improve the sensitivity of uCyt+alone. If UC was based upon a positive uCyt+test, 8/33 tumors (24.2%) would have been overlooked or diagnosed late. In contrast, 173 UCs (74%) would have been saved and 5 presumably unnecessary TURB procedures would not have been indicated. CONCLUSIONS: This longitudinal study suggests a potential of molecular urine tests in replacing cystoscopy in the follow-up of patients with pTa G1-2 bladder cancer. The use of additional markers might further improve sensitivity of urine testing. A prospective randomized study has been initiated to prospectively investigate the performance of a marker panel against UC.

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.