What is the evaluation and treatment approach for a patient with bladder pain and microhematuria?

Evaluation and Management of Bladder Pain with Microhematuria

All patients with bladder pain and microhematuria require risk stratification using the 2025 AUA/SUFU criteria, followed by cystoscopy and upper tract imaging for intermediate- or high-risk patients, while simultaneously evaluating for interstitial cystitis as a potential cause of the bladder pain. 1

Initial Assessment

Perform a focused history targeting:

• Smoking history (quantify pack-years: <10-30, or >30) as this is the strongest modifiable risk factor for urothelial malignancy 1
• Age and sex (men ≥40 years and women ≥60 years have elevated risk) 1
• Irritative voiding symptoms (urgency, frequency, nocturia) which may indicate interstitial cystitis or bladder cancer 1, 2
• Occupational exposures to benzenes, aromatic amines, or other chemical carcinogens 2
• History of gross hematuria (even if not currently present) 1
• Chronic pelvic pain patterns particularly in women, as interstitial cystitis is prevalent but often underdiagnosed 1

Physical examination should include:

• Blood pressure measurement to assess for renal parenchymal disease 1
• Pelvic examination in women to exclude gynecologic causes 1
• Rectal examination in men to assess prostate 1

Obtain serum creatinine to evaluate renal function 1, 2

Confirm True Hematuria and Exclude Benign Causes

Microscopic urinalysis is mandatory to confirm ≥3 RBCs/HPF, as dipstick alone has limited specificity (65-99%) and can yield false positives from myoglobinuria or menstrual contamination 3

If urinary tract infection is suspected:

• Obtain urine culture before starting antibiotics 1, 2
• Treat appropriately and repeat urinalysis 6 weeks post-treatment 1, 2
• If hematuria resolves, no further evaluation is needed 1

Exclude other benign causes by repeating urinalysis 48 hours after cessation of:

• Menstruation 2
• Vigorous exercise 1, 2
• Sexual activity 2
• Recent urologic procedures 1

Critical pitfall: Do not attribute hematuria solely to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves 4

Risk Stratification Using 2025 AUA/SUFU Criteria

Categorize patients based on the following algorithm 1:

Low/Negligible Risk (0-0.4% malignancy risk) - ALL criteria must be met:

• 3-10 RBC/HPF on single urinalysis
• Women <60 years OR men <40 years
• Never smoker or <10 pack-years

Intermediate Risk (0.2-3.1% malignancy risk) - ONE or more criteria:

• 11-25 RBC/HPF
• Women ≥60 years OR men 40-59 years
• 10-30 pack-years smoking history

High Risk (1.3-6.3% malignancy risk) - ONE or more criteria:

• 25 RBC/HPF

• Men ≥60 years

• 30 pack-years smoking history

• History of gross hematuria with 3-25 RBC/HPF on repeat urinalysis 1

Evaluate for Glomerular vs. Non-Glomerular Source

Examine urinary sediment for 2, 3:

• Dysmorphic RBCs (>80% suggests glomerular source)
• Red cell casts (pathognomonic for glomerular disease)
• Proteinuria (>500 mg/24 hours suggests glomerular disease)

If glomerular source is suspected (dysmorphic RBCs >80%, red cell casts, proteinuria >500 mg/24 hours, or elevated creatinine):

• Refer to nephrology for evaluation of medical renal disease 2, 3
• However, this does not exclude concurrent urologic malignancy—proceed with urologic evaluation as well 4

Urologic Evaluation Based on Risk Category

For Intermediate or High-Risk Patients:

Cystoscopy is mandatory to visualize the bladder and urethra, as most cancers in hematuria patients are bladder cancers optimally detected by direct visualization 1

Upper tract imaging:

• CT urography (CTU) is the preferred modality with 92% sensitivity and 93% specificity for urologic pathology 1, 4, 5
• CTU should include unenhanced images followed by nephrographic and excretory phases (at least 5 minutes post-contrast) with thin-slice acquisition 1
• Alternative: MR urography if CT is contraindicated 1

Urine cytology should be obtained in patients with risk factors for transitional cell carcinoma 1

For Low/Negligible-Risk Patients:

The 2025 AUA/SUFU guidelines provide updated recommendations for this group, though the specific management algorithm requires clinical judgment based on the complete guideline 1

Special Consideration: Interstitial Cystitis

Bladder pain with hematuria may indicate interstitial cystitis (IC), particularly in women with chronic pelvic pain 1

Key features of IC:

• Hematuria occurs in up to 30-41% of IC patients 6
• Characterized by irritative voiding symptoms (urgency, frequency, nocturia) and pelvic/bladder pain 1, 7
• Diagnosis requires cystoscopy showing Hunner's ulcers or glomerulations with bladder biopsy 7, 6

Important: Even in confirmed IC, hematuria evaluation is unlikely to reveal life-threatening conditions, but complete evaluation should still be performed in intermediate/high-risk patients 6

Treatment of IC (if diagnosed):

• Pentosan polysulfate (Elmiron) 100 mg three times daily is FDA-approved 7
• In clinical trials, 38% of patients showed >50% improvement in bladder pain at 3 months (vs. 18% placebo, p=0.005) 7
• Most patients who respond show improvement within 3-6 months 7

Follow-Up for Persistent Hematuria

If initial evaluation is negative but hematuria persists:

• Repeat urinalysis at 6,12,24, and 36 months 2
• Monitor blood pressure at each visit 2
• Consider nephrology referral if hematuria persists with development of hypertension, proteinuria, or evidence of glomerular bleeding 2

Critical Pitfalls to Avoid

• Women are significantly underreferred for hematuria evaluation (8-28% referral rate vs. 36-47% in men) despite similar cancer risk—do not assume hematuria is due to menstruation without verification 4
• Delays in bladder cancer diagnosis contribute to 34% increased cancer-specific mortality and 15% increased all-cause mortality 1
• Do not rely solely on imaging—cystoscopy is essential as bladder cancers are the most common malignancy in hematuria patients 1
• Anticoagulation is not an excuse to defer evaluation—these patients have the same underlying malignancy risk 4