Evaluation and Management of Hematuria in Men

Immediate Triage: Gross vs. Microscopic Hematuria

All men with gross (visible) hematuria require urgent urologic referral with cystoscopy and upper tract imaging, regardless of whether bleeding is self-limited, due to a 30-40% malignancy risk. 1, 2

Critical First Step: Confirm True Hematuria

Do not proceed with any workup based on dipstick alone—dipstick testing has only 65-99% specificity and produces false positives from myoglobin, hemoglobin, povidone-iodine, and certain medications. 1, 2, 3
Microscopic confirmation is mandatory: Obtain properly collected clean-catch midstream urine specimen and verify ≥3 red blood cells per high-power field (RBC/HPF) on microscopic examination. 1, 2, 4
For microscopic hematuria, confirm on at least 2 of 3 properly collected specimens before initiating extensive workup, unless high-risk features are present (then proceed after single positive specimen). 1, 2, 4

Exclude Transient Benign Causes Before Full Workup

Reversible Causes to Rule Out First:

Urinary tract infection: If pyuria, dysuria, or positive nitrites present, obtain urine culture (preferably before antibiotics), treat appropriately, then repeat urinalysis 6 weeks after treatment completion. 1, 2, 4
- If hematuria resolves after treating infection, no further evaluation needed. 2, 4
- If hematuria persists after infection treatment, proceed with full urologic evaluation. 2, 4
Recent vigorous exercise: Repeat urinalysis 48 hours after cessation of activity. 1, 2, 4
Recent sexual activity or minor trauma: Repeat urinalysis after 48 hours. 1, 4
Medications causing pseudohematuria: Phenazopyridine (Azo) causes orange-red discoloration—discontinue 48-72 hours before urinalysis and repeat testing. 3

Critical Caveat About Anticoagulation:

Never attribute hematuria to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves, and evaluation must proceed regardless. 1, 2, 4

Risk Stratification for Malignancy

High-Risk Features (Require Full Urologic Evaluation):

Age ≥60 years (automatic high-risk in men) 1, 2, 4
Smoking history >30 pack-years 1, 2, 4
Any history of gross hematuria (even if self-limited or remote) 1, 2
>25 RBCs/HPF on microscopic examination 2, 4
Occupational exposure to benzenes, aromatic amines, or other chemicals/dyes 1, 2, 4
Irritative voiding symptoms without infection (urgency, frequency, nocturia) 1, 2, 4
History of pelvic irradiation 4
History of chronic analgesic use 4

Intermediate-Risk Features:

Age 40-59 years 2, 4
Smoking history 10-30 pack-years 2, 4
11-25 RBCs/HPF 2, 4

Low-Risk Features:

Age <40 years 2, 4
Never smoker or <10 pack-years 2, 4
3-10 RBCs/HPF 2, 4

Distinguish Glomerular from Non-Glomerular Sources

Indicators of Glomerular Disease (Nephrology Referral):

Tea-colored or cola-colored urine (not bright red) 1, 2, 4
Significant proteinuria: Spot urine protein-to-creatinine ratio >0.5 g/g or >500 mg/24 hours 1, 2, 4
Dysmorphic RBCs >80% on phase-contrast microscopy 1, 2, 4
Red blood cell casts (pathognomonic for glomerular disease) 1, 2, 4
Elevated serum creatinine or declining renal function 1, 2, 4
Hypertension accompanying hematuria 1, 2, 4

If Glomerular Features Present:

Refer to nephrology in addition to completing urologic evaluation—glomerular disease does not exclude concurrent malignancy. 1, 2, 4
Obtain complete metabolic panel, complement levels (C3, C4), ANA, and ANCA if vasculitis suspected. 2

Complete Urologic Evaluation for Non-Glomerular Hematuria

Laboratory Testing:

Serum creatinine and complete metabolic panel to assess renal function 1, 2, 4
Complete urinalysis with microscopy examining for dysmorphic RBCs, casts, crystals 1, 2, 4
Urine culture if infection suspected 1, 2, 4
Do NOT obtain voided urine cytology in initial evaluation—not recommended by current guidelines and lacks sensitivity to obviate further workup. 2, 5

Upper Tract Imaging:

Multiphasic CT urography is the preferred imaging modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis in intermediate- and high-risk patients. 1, 2, 4

Includes unenhanced, nephrographic phase, and excretory phase images. 2
Renal ultrasound alone is insufficient for comprehensive upper tract evaluation—detects only 75% of urinary tract stones and 38% of ureteral stones. 2

Alternative imaging if CT contraindicated:

MR urography for patients with contrast allergy 2
Renal ultrasound with retrograde pyelography for patients with renal insufficiency 2

Lower Tract Evaluation:

Cystoscopy is mandatory for:

All patients with gross hematuria 1, 2, 4
All men ≥40 years with microscopic hematuria 2, 4
Microscopic hematuria patients with any high-risk features 1, 2, 4

Flexible cystoscopy is preferred over rigid cystoscopy—causes less pain, fewer post-procedure symptoms, and demonstrates equivalent or superior diagnostic accuracy. 2, 4

Management Based on Risk Category

High-Risk Patients:

Proceed immediately with cystoscopy and CT urography after confirming microscopic hematuria on single properly collected specimen. 2, 4

Intermediate-Risk Patients:

Shared decision-making about cystoscopy and imaging—discuss risks/benefits with patient, but strongly consider full evaluation given 2.6-4% overall malignancy risk (up to 25.8% in at-risk populations). 2, 4, 6

Low-Risk Patients:

May undergo repeat urinalysis in 6 months or proceed with evaluation based on patient preference. 4
However, if hematuria persists on repeat testing, proceed with full evaluation. 4

Follow-Up Protocol for Negative Initial Evaluation

If Complete Workup is Negative but Hematuria Persists:

Repeat urinalysis at 6,12,24, and 36 months 1, 2, 4
Monitor blood pressure at each visit 1, 2, 4
Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients 2, 4
After two consecutive negative annual urinalyses, no further testing necessary for asymptomatic microhematuria 2

Immediate Re-Evaluation Warranted If:

Gross hematuria develops 1, 2, 4
Significant increase in degree of microscopic hematuria 1, 2, 4
New urologic symptoms appear (flank pain, dysuria, irritative voiding symptoms) 1, 2, 4
Development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2, 4

Common Pitfalls to Avoid

Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates urgent urologic referral. 1, 2
Do not defer evaluation due to anticoagulation—malignancy risk is similar regardless of anticoagulation status. 1, 2, 4
Do not rely solely on dipstick testing—confirm with microscopic urinalysis showing ≥3 RBCs/HPF before initiating workup. 1, 2, 3
Do not prescribe empiric antibiotics for hematuria without documented infection—this delays cancer diagnosis and provides false reassurance. 2
Do not stop at symptom resolution alone—documented microscopic confirmation of resolution of hematuria is required after treating presumed benign causes. 4
Women are substantially undertreated—despite higher case-fatality rates for bladder cancer, women have lower referral rates and longer delays to evaluation. 1
Specifically inquire about history of visible hematuria in routine review of systems—19.8% of patients with microscopic hematuria report prior gross hematuria when directly asked, which carries an odds ratio of 7.2 for urologic cancer. 1, 4

What is the appropriate evaluation and management approach for a male patient presenting with hematuria?

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