Longitudinal follow-up and performance validation of an mRNA-based urine test (Xpert® Bladder Cancer Monitor ) for surveillance in patients with non-muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the performance of the Xpert Bladder Cancer Monitor (Xpert; Cepheid, Sunnyvale, CA, USA) test as a predictor of tumour recurrence in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patients (n = 429) undergoing surveillance for NMIBC underwent Xpert, cytology, and UroVysion testing. Patients with a positive Xpert and a negative cystoscopy result (positive-negative [PN] group, n = 66) and a control group of double negative patients (negative Xpert and cystoscopy results [NN] group) were followed for 12 months (±90 days). RESULTS: Histology-confirmed recurrences were detected in 58 patients (13.5%). Xpert had an overall sensitivity of 60.3% and a specificity of 76.5%. The sensitivity for high-grade (HG) cancer was 87% with a negative predictive value (NPV) of 99%. Urine cytology showed an overall sensitivity of 23.2% (47.6% sensitivity for HG tumours) and a specificity of 88.3%. In the PN group, 32% (n = 21) developed a recurrence within 12 months, 11 of which were HG tumours. In the NN control group, 14% (n = 9) developed a recurrence and only two were HG tumours. The hazard ratio for developing recurrence in the PN group was 2.68 for all tumours and 6.84 for HG cancer. CONCLUSIONS: The Xpert test has a high sensitivity for detecting the recurrence of cancer and a high NPV for excluding HG cancer. In addition, the data suggest that patients with a positive Xpert assay in the setting of negative cystoscopy are at high risk for recurrence and need close surveillance.

Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium.

PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is a putative precursor of invasive prostate cancer (PCa). Preclinical evidence suggests vitamin E, selenium, and soy protein may prevent progression of HGPIN to PCa. This hypothesis was tested in a randomized phase III double-blind study of daily soy (40 g), vitamin E (800 U), and selenium (200 µg) versus placebo. PATIENTS AND METHODS: Three hundred three men in 12 Canadian centers were analyzed. The main eligibility criterion was confirmed HGPIN in at least one of two biopsies within 18 months of random assignment. Treatment was administered daily for 3 years. Follow-up prostate biopsies occurred at 6, 12, 24, and 36 months postrandomization. The primary end point was time to development of invasive PCa. Kaplan-Meier plots and log-rank tests were used to compare two treatment groups for this end point. RESULTS: For all patients, the median age was 62.8 years. The median baseline prostate-specific antigen (PSA; n = 302) was 5.41 ug/L; total testosterone (n = 291) was 13.4 nmol/L. Invasive PCa developed among 26.4% of patients. The hazard ratio for the nutritional supplement to prevent PCa was 1.03 (95% CI, 0.67 to 1.60; P = .88). Gleason score distribution was similar in both groups with 83.5% of cancers graded Gleason sum of 6. Baseline age, weight, PSA, and testosterone did not predict for development of PCa. The supplement was well tolerated with flatulence reported more frequently (27% v 17%) among men receiving micronutrients. CONCLUSION: This trial does not support the hypothesis that combination vitamin E, selenium, and soy prevents progression from HGPIN to PCa.

Use of a multitarget fluorescence in situ hybridization assay to diagnose bladder cancer in patients with hematuria.

PURPOSE: We evaluated the multitarget UroVysion fluorescence in situ hybridization assay for the diagnosis of bladder cancer in patients with hematuria and no history of bladder cancer. MATERIALS AND METHODS: A multicenter, blinded trial was performed to compare the sensitivity of the fluorescence in situ hybridization assay to that of voided cytology in patients with gross or microscopic hematuria. Confirmation of hematuria was required. Voided urine was sent to a central laboratory for each study before cystoscopy. Suspicious lesions on cystoscopy were biopsied or resected. A centrally reviewed histopathological interpretation was used to confirm cancer and assign grade and stage. RESULTS: A total of 497 patients were enrolled at 23 centers and in 473 (95.2%) fluorescence in situ hybridization and cytology results were interpretable. Bladder cancer was diagnosed histologically in 50 patients (10.1%) and ureteral cancer was diagnosed in 1. Fluorescence in situ hybridization assay detected 69% of cases and cytology detected 38% (95% CI 25 to 52). When low grade, low stage (TaG1) tumors were excluded, fluorescence in situ hybridization detected 25 of 30 cancers (84%), while cytology detected only 15 (50%). Of 265 current or past smokers with hematuria and positive fluorescence in situ hybridization assay findings bladder cancer was detected in 65% with a history of greater than 40 pack-years compared to 13.6% to 24.2% in those with no, less than a 20 or a 20 to 40-pack-year smoking history. CONCLUSIONS: The UroVysion fluorescence in situ hybridization assay is significantly more sensitive than voided cytology for detecting bladder cancer in patients evaluated for gross or microscopic hematuria for all grades and stages. Based on these data UroVysion was approved by the Food and Drug Administration for use in patients with hematuria.