What is the appropriate workup for hematuria in a male patient?

Workup for Hematuria in Adult Males

In adult males with hematuria, the workup must be risk-stratified and aggressive, with the primary goal of excluding malignancy—particularly in men over 40 years or those with gross hematuria, where cancer risk reaches 30-40%. 1, 2

Step 1: Confirm True Hematuria

• Verify microscopic hematuria with ≥3 RBCs per high-power field on at least two of three properly collected clean-catch midstream urine specimens before initiating any extensive workup 1, 3
• Dipstick testing alone has only 65-99% specificity and produces false positives from myoglobin, hemoglobin, or menstrual contamination—microscopic confirmation is mandatory 1, 3
• For gross (visible) hematuria, proceed immediately to urgent urologic evaluation without waiting for repeat specimens 1, 4

Step 2: Initial Laboratory Assessment

• Complete urinalysis with microscopy examining for dysmorphic RBCs (>80% suggests glomerular source), red cell casts (pathognomonic for glomerular disease), white blood cells, and bacteria 1, 3
• Urine culture if infection suspected—preferably before antibiotics 1, 2
• Serum creatinine and complete metabolic panel to assess renal function 1, 3
• Spot urine protein-to-creatinine ratio if proteinuria is present on dipstick (>0.5 g/g suggests renal parenchymal disease) 1

Step 3: Risk Stratification for Malignancy

HIGH-RISK Features (Require Full Urologic Evaluation)

• Any episode of gross hematuria (30-40% malignancy risk) 1, 2, 4
• Age ≥60 years 1
• Smoking history >30 pack-years 1, 2
• Occupational exposure to benzenes, aromatic amines, or other bladder carcinogens 1, 2
• Irritative voiding symptoms without documented infection 1
• Microscopic hematuria >25 RBCs/HPF 1
• History of prior gross hematuria 1

INTERMEDIATE-RISK Features

• Age 40-59 years 1
• Smoking history 10-30 pack-years 1

LOW-RISK Features

• Age <40 years 1
• Never smoker or <10 pack-years 1
• 3-10 RBCs/HPF 1

Step 4: Distinguish Glomerular vs. Urologic Source

Glomerular Indicators (Require Nephrology Referral)

• Dysmorphic RBCs >80% or red cell casts on microscopy 1, 2, 3
• Protein-to-creatinine ratio >0.5 g/g (or >500 mg/24h) 1
• Tea-colored or cola-colored urine 1, 2
• Elevated serum creatinine or declining renal function 1
• Hypertension accompanying hematuria 1

If glomerular features are present, refer to nephrology in addition to completing urologic evaluation—malignancy can coexist with medical renal disease 1

Non-Glomerular Indicators (Proceed with Urologic Workup)

• Normal-shaped RBCs >80% 2
• Absence of significant proteinuria 2
• Bright red urine (suggests lower urinary tract bleeding) 1

Step 5: Complete Urologic Evaluation (for High-Risk or Intermediate-Risk Patients)

Upper Tract Imaging

• Multiphasic CT urography is the preferred modality, including unenhanced (detects calculi), nephrographic (evaluates renal parenchyma), and excretory phases (assesses urothelium) 1, 3
• If CT contraindicated (severe renal insufficiency or contrast allergy), use MR urography or renal ultrasound with retrograde pyelography 1
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation 1

Lower Tract Evaluation

• Flexible cystoscopy is mandatory for all men ≥40 years with microscopic hematuria and all men with gross hematuria, regardless of age 1, 2, 3
• Flexible cystoscopy is preferred over rigid cystoscopy—causes less pain with equivalent or superior diagnostic accuracy 1
• Cystoscopy visualizes bladder mucosa, urethra, and ureteral orifices to detect transitional cell carcinoma (the most frequently diagnosed malignancy in hematuria cases) 1, 2

Urine Cytology

• Consider voided urine cytology in high-risk patients (age >60 years, smoking >30 pack-years, occupational exposures) as an adjunct to cystoscopy 1, 3
• Do not use cytology as the initial or sole evaluation tool—it is not sensitive enough to obviate further workup if negative 1, 5

Step 6: Special Clinical Scenarios

Hematuria with Urinary Tract Infection

• Obtain urine culture before starting antibiotics 1
• If hematuria resolves within 6 weeks after completing antibiotics in a low-risk patient, no further workup is needed 1
• If hematuria persists after infection treatment, proceed immediately with complete urologic evaluation—infection may mask malignancy 1

Hematuria on Anticoagulation/Antiplatelet Therapy

• Do not attribute hematuria to anticoagulation—these medications may unmask underlying pathology but do not cause hematuria 1, 3
• Evaluation must proceed regardless of medication use 1, 4

Benign Prostatic Hyperplasia (BPH)

• BPH can cause hematuria but does not exclude concurrent malignancy—gross hematuria from BPH must be proven through appropriate evaluation 1, 2

Step 7: Follow-Up Protocol for Negative Initial Evaluation

• If initial workup is negative but hematuria persists, repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 1, 3
• After two consecutive negative annual urinalyses, no further testing is necessary 1
• Immediate re-evaluation is warranted if:
  • Gross hematuria develops 1
  • Significant increase in microscopic hematuria occurs 1
  • New urologic symptoms appear 1
  • Hypertension, proteinuria, or evidence of glomerular bleeding develops 1

Critical Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates urgent urologic referral 1, 2, 4
• Do not rely solely on dipstick testing—confirm with microscopic urinalysis showing ≥3 RBCs/HPF 1, 3
• Do not defer evaluation due to anticoagulation or presumed benign causes in high-risk patients 1, 3
• Do not assume BPH explains hematuria without complete evaluation 1
• Delays in diagnosis beyond 9 months are associated with worse cancer-specific survival 1