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AIM: To evaluate prospectively a clinical pathway for investigation of haematuria that involves an initial screening using a urinary biomarker of bladder cancer (Cxbladder Triage™ (CxbT)) in combination with either a renal ultrasound or a computed tomography imaging. Only test-positive patients are referred for specialist assessment and flexible cystoscopy. METHODS: The clinical outcomes of 884 patients with haematuria who presented to their general practitioner were reviewed. Outcome measurements included the findings of laboratory tests, imaging, cystoscopies, specialist assessment and histology. RESULTS: Forty-eight transitional cell carcinomas (TCC) and three small cell carcinomas were diagnosed in the study cohort. The clinical pathway missed a solitary, small, low-risk TCC. When combined, imaging and CxbT had a sensitivity of 98.1% and a negative predictive value of 99.9% to detect a bladder cancer. Follow-up for a median of 21 months showed no further new cases of bladder cancer had occurred in the patient cohort. Review of all new bladder cancers diagnosed in the 15 months following the study showed that none had been missed by haematuria assessment using the clinical pathway. CONCLUSIONS: The combination of CxbT and imaging reliably identifies patients with haematuria who can be managed safely in primary care without the need for a secondary care referral and a flexible cystoscopy.