Outcomes of a Bladder Cancer Screening Program Using Home Hematuria Testing and Molecular Markers

• Published in: European urology Vol. 64; no. 1; pp. 41 - 47
• Main Authors: Bangma, Chris H, Loeb, Stacy, Busstra, Martijn, Zhu, Xiaoye, El Bouazzaoui, Samira, Refos, Jeanine, Van Der Keur, Kirstin A, Tjin, Stephen, Franken, Conja G.A.M, van Leenders, Geert J.L.H, Zwarthoff, Ellen C, Roobol, Monique J
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.07.2013; Elsevier
• Subjects: Aged; Biological and medical sciences; Biomarkers - urine; Bladder cancer; Chi-Square Distribution; Cystoscopy; DNA Methylation; Feasibility Studies; Genetic Markers; Genetic Testing - instrumentation; Hematuria; Hematuria - diagnosis; Hematuria - etiology; Hematuria - genetics; Humans; Male; Mass Screening - instrumentation; Mass Screening - methods; Medical sciences; Microsatellite Instability; Middle Aged; Nephrology. Urinary tract diseases; Netherlands; NMP22, FGFR3, cystoscopy; Nuclear Proteins - urine; Patient Selection; Predictive Value of Tests; Prognosis; Reagent Strips; Receptor, Fibroblast Growth Factor, Type 3 - genetics; Registries; Reproducibility of Results; Risk Assessment; Risk Factors; Screening; Self Care - instrumentation; Tumors of the urinary system; Unnecessary Procedures; Urinalysis - instrumentation; Urinary Bladder Neoplasms - complications; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - urine; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Urology; Netherlands; Screening; Hematuria; NMP22, FGFR3, cystoscopy; Bladder cancer; Nephrology; Urinary system disease; Program; Prognosis; Genetic marker; Cystoscopy; Urinary tract disease; Malignant tumor; Molecular marker; Medical screening; Hemorrhage; Urology; Bladder disease; Cancer; Fibroblast growth factor receptor 3
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2013.02.036

Abstract Background We previously reported the preliminary findings from a feasibility study of bladder cancer (BCa) screening with urinary molecular markers (Bladder Cancer Urine Marker Project [BLU-P]) that has now been terminated. Objective To report the final results from BLU-P to determine whether mass screening for BCa is feasible and useful. Design, setting, and participants BLU-P was a Dutch population-based study initiated in 2008 to evaluate BCa screening. A total of 6500 men were invited to participate in the study, 1984 (30.5%) agreed, and 1747 (88.1%) men completed the protocol and were followed for 2 yr. Intervention The screening protocol included home hematuria testing followed by molecular markers—nuclear matrix protein 22 (NMP22), microsatellite analysis (MA), fibroblast growth factor receptor 3 (FGFR3) mutation snapshot assay, and a custom methylation-specific (MLPA) test—to determine the need for cystoscopy. Outcome measurements and statistical analysis Outcomes included the number of cystoscopies and the cancer detection rate within and outside the protocol, as determined by linkage to national registries. Results and limitations Overall, 409 men (23.4%) tested positive for hematuria and underwent molecular testing. Current smokers ( n = 295 [17%]) and past smokers ( n = 998 [58%]) were significantly more likely to test positive for hematuria than nonsmokers. Seventy-one of 75 men (94.6%) with positive molecular markers underwent the recommended cystoscopy. Four BCas and one kidney tumor were detected through this sequential protocol, whereas one BCa and one kidney tumor were missed through the screening program. Limitations include the possibility of healthy subject bias. Conclusions For BCa screening, use of a sequential protocol with home hematuria testing followed by molecular markers substantially reduced the number of cystoscopy recommendations compared with dipstick testing alone. A sequential screening approach may help minimize unnecessary invasive follow-up testing, with very few missed cancers. Nevertheless, this mass screening program had a very low diagnostic yield in an unselected asymptomatic European male population.