What is the next step in managing a male patient with a history of urinary tract infection (UTI), presenting with dysuria, urinary hesitancy, occasional hematuria, and proteinuria, with negative urinalysis for leukocytes, nitrates, and blood, but positive for bilirubin and ketones, and symptoms of urinary urgency and frequency?

Urgent Urologic Referral for Cystoscopy and Upper Tract Imaging

This patient requires immediate urologic evaluation with cystoscopy and upper tract imaging (CT urography), as his presentation strongly suggests bladder pathology—most concerning for bladder cancer or chronic interstitial cystitis—rather than a simple urinary tract infection. 1

Critical Red Flags in This Presentation

The constellation of findings demands urgent action:

• History of hematuria (even if occasional) in a male patient is a high-risk feature requiring complete urologic evaluation regardless of current urinalysis results 1
• Chronic symptoms persisting for several months despite presumed UTI treatment indicates this is not infectious cystitis 2
• Irritative voiding symptoms (urgency, frequency, dysuria) without documented infection are high-risk features for urologic malignancy and mandate full evaluation 1
• Negative urinalysis for leukocytes and nitrites effectively rules out active bacterial UTI, making the "previous UTI diagnosis" questionable 3

Why the Urinalysis Results Are Misleading

The current urinalysis findings do not support UTI:

• Absence of leukocytes and nitrites makes bacterial UTI extremely unlikely 3
• Positive bilirubin and ketones are non-specific and do not indicate urinary tract pathology 4
• Proteinuria without hematuria on dipstick (despite reported occasional visible blood) suggests either intermittent bleeding or false-positive dipstick results 1
• The discordance between reported hematuria and negative dipstick for blood requires microscopic urinalysis confirmation with ≥3 RBCs/HPF 1

Mandatory Next Steps

Immediate Urologic Referral (Do Not Delay)

Refer to urology urgently for:

• Cystoscopy to visualize bladder mucosa and exclude transitional cell carcinoma, carcinoma in situ, or interstitial cystitis 1, 2
• Multiphasic CT urography to evaluate upper tracts for malignancy, stones, or structural abnormalities 1
• Voided urine cytology given the high-risk presentation with chronic irritative symptoms 1

Before Urologic Appointment

• Obtain microscopic urinalysis to confirm true hematuria (≥3 RBCs/HPF) versus false-positive dipstick 1
• Send urine culture to definitively exclude UTI, though negative leukocytes/nitrites make this unlikely 2, 3
• Check serum creatinine and BUN to assess renal function 1
• Do NOT empirically treat with antibiotics without culture confirmation, as this may mask underlying pathology 2

Differential Diagnoses to Consider

Most Likely (Requiring Urgent Evaluation)

• Bladder cancer (transitional cell carcinoma): Chronic irritative symptoms with hematuria in males is classic presentation 1
• Carcinoma in situ: Can present with severe irritative symptoms mimicking UTI 1
• Interstitial cystitis/bladder pain syndrome: Chronic symptoms without infection, but diagnosis of exclusion after malignancy ruled out 2

Less Likely But Important

• Bladder stones: Can cause chronic irritation and hematuria 1
• Chronic prostatitis: Though suprapubic rather than perineal pain makes this less likely 5
• Urethral stricture: May cause hesitancy and dysuria 5

Unlikely Given Presentation

• Acute UTI: Negative leukocytes/nitrites essentially exclude this 3
• Glomerulonephritis: Would expect dysmorphic RBCs, proteinuria with hematuria, and systemic signs 1

Critical Pitfalls to Avoid

• Never attribute chronic hematuria to "resolved UTI" without complete urologic evaluation—30-40% of gross hematuria cases are malignant 1
• Do not repeat empiric antibiotic courses without culture-proven infection, as this delays diagnosis of serious pathology 2
• Do not assume negative dipstick for blood excludes hematuria—intermittent bleeding requires microscopic confirmation 1
• Do not delay referral while attempting conservative management—chronic irritative symptoms in males warrant urgent cystoscopy 1, 2

Why This Cannot Wait

Bladder cancer can present with irritative voiding symptoms that mimic UTI for months before diagnosis, and delay in cystoscopy directly impacts prognosis 1. The combination of reported hematuria, chronic symptoms despite treatment, and male gender places this patient at high risk requiring immediate evaluation rather than watchful waiting 1.