What is the most appropriate next step to diagnose the cause of consistent hematuria in a hypertensive and diabetic man with a history of smoking and alcohol consumption?

Cystoscopy with Upper Tract Imaging (CT Urography) is Most Likely to Confirm the Diagnosis

This patient requires urgent complete urologic evaluation with cystoscopy and multiphasic CT urography to evaluate for bladder cancer and upper tract urothelial malignancy. 1, 2

Why This Patient is High-Risk for Urologic Malignancy

This patient has multiple high-risk features that mandate comprehensive urologic evaluation:

• Age ≥60 years - automatically classifies him as high-risk regardless of other factors 1, 3
• Male sex - associated with higher prevalence of significant urologic disease 1
• Smoking history - a critical risk factor for urothelial carcinoma 1, 2
• Persistent gross hematuria - carries a 30-40% risk of malignancy and requires urgent evaluation even if self-limited 2, 3
• Diabetes and hypertension - while these conditions themselves don't cause hematuria, they place him in a category already at increased cardiovascular risk 1

Why Antibiotics Failed and What This Means

The 2-month duration of symptoms despite appropriate antibiotic therapy effectively rules out simple urinary tract infection as the sole cause. 2 Prescribing additional antibiotics would delay cancer diagnosis and provide false reassurance. 2 The progression from sporadic to consistent hematuria despite treatment strongly suggests a non-infectious etiology such as urologic cancer. 2

The Complete Urologic Evaluation Required

Upper Tract Imaging: Multiphasic CT Urography

Multiphasic CT urography is the preferred imaging modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis in high-risk patients. 1, 2, 3 This includes:

• Unenhanced phase
• Nephrographic phase
• Excretory phase 2

This comprehensive approach evaluates kidneys, collecting systems, ureters, and bladder for hydronephrosis, urinary calculi, and renal/ureteral lesions. 1, 2

Lower Tract Evaluation: Cystoscopy

Cystoscopy is mandatory for all patients with gross hematuria to evaluate for bladder masses, urethral stricture disease, and benign prostatic hyperplasia. 1, 2, 3 Flexible cystoscopy is preferred over rigid cystoscopy as it causes less pain with equivalent or superior diagnostic accuracy. 2, 3

Additional Testing

• Voided urine cytology should be obtained in this high-risk patient to detect high-grade urothelial carcinomas and carcinoma in situ 2, 3
• Serum creatinine to assess renal function 1, 3
• Complete urinalysis with microscopy to examine for dysmorphic RBCs or red cell casts that would suggest glomerular disease 1, 3

Critical Pitfalls to Avoid

Never attribute hematuria to medications alone. While this patient takes hydrochlorothiazide, lisinopril, and metformin, none of these medications cause hematuria—they may only unmask underlying pathology that requires investigation. 2, 3 Evaluation must proceed regardless of medication use. 2

Do not defer evaluation due to identified "benign" causes. Even if benign prostatic hyperplasia is found on exam, this does not exclude concurrent malignancy. 2 Gross hematuria from BPH must be proven to be of prostatic etiology through appropriate evaluation. 2

Early detection significantly impacts mortality and morbidity. Delays in diagnosis beyond 9 months from first hematuria presentation are associated with worse cancer-specific survival in bladder cancer patients. 2 Evaluation should not be delayed in high-risk patients. 1

When to Consider Nephrology Referral

While urologic evaluation takes priority, nephrology referral is indicated if there are signs of renal parenchymal disease: 1, 3

• Significant proteinuria (>500-1000 mg/24 hours) 1, 3
• Dysmorphic RBCs >80% or red cell casts 1, 3
• Elevated serum creatinine 1, 3

However, the presence of glomerular features does not eliminate the need for urologic evaluation—both evaluations should be completed, as malignancy can coexist with medical renal disease. 2

Why Other Tests Are Insufficient

• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation and has limited sensitivity for small renal masses 2
• Repeat urinalysis would only delay diagnosis in a patient with persistent gross hematuria 2
• Urine culture is not indicated when infection has already been treated without resolution of hematuria 2