How many urine cytology repetitions (reps) should be ordered for a high-risk patient with a history of smoking or carcinogen exposure?

Urine Cytology Ordering in High-Risk Patients

Do not routinely order urine cytology for initial hematuria evaluation, even in high-risk patients with smoking or carcinogen exposure—proceed directly to cystoscopy and imaging instead. 1

Primary Recommendation: Cytology is NOT Routine

The 2025 AUA/SUFU guidelines explicitly state that clinicians should not routinely use urine cytology or urine-based tumor markers to decide whether to perform cystoscopy in the initial evaluation of low/negligible- or high-risk patients with microhematuria. 1 This represents a strong recommendation with Grade C evidence. 1

The rationale is clear from the DETECT I study: among 3,556 patients with hematuria, no bladder cancer or upper tract urothelial carcinoma was diagnosed based on suspicious urinary cytology alone. 1 When 22 patients had positive cytology despite normal cystoscopy and imaging, 12 underwent additional invasive procedures, yet no malignancies were identified. 1

When Cytology MAY Be Considered (Limited Scenarios)

Scenario 1: Persistent Hematuria After Negative Workup

In patients with persistent microhematuria following a negative initial workup who have additional risk factors for carcinoma in situ (irritative voiding symptoms, current or past tobacco use, chemical exposures), cytology may be useful as an adjunctive test. 1 However, a negative cytology does not preclude full workup. 1

Scenario 2: Normal Cystoscopy with High CIS Suspicion

Clinicians should not routinely use cytology as an adjunctive test in the setting of a normal cystoscopy. 1 The 2025 guidelines make this a strong recommendation. 1

Performance Characteristics: Why Cytology Fails as Screening

The evidence demonstrates poor reliability:

• Sensitivity: 57.7% (meaning 42% of cancers are missed) 1
• Specificity: 94.9% 1
• Negative predictive value: 95.0%-98.7% in microhematuria populations 1
• Historical data shows sensitivity ranging from 0% to 100% across studies 1

Cytology is likely to produce false negatives but unlikely to produce false positives. 1 This means it misses cancers but when positive, warrants attention—yet this doesn't justify routine use given the superior diagnostic yield of direct cystoscopy.

The Correct Approach for High-Risk Patients

For your patient with smoking history or carcinogen exposure:

1. Confirm true hematuria: ≥3 RBCs/HPF on microscopic examination 2, 3

2. Proceed directly to:

   • Multiphasic CT urography for upper tract evaluation 2, 3
   • Cystoscopy (flexible preferred) for bladder visualization 2, 3

3. Skip cytology in the initial evaluation 1

4. Consider cytology only if:

   • Initial workup is completely negative AND
   • Hematuria persists AND
   • High suspicion for carcinoma in situ remains 1

Critical Pitfall to Avoid

Never use cytology results to decide whether to perform cystoscopy. 1 The 2012 guidelines noted that cytology lacks sufficient clinical reliability for routine evaluation, with the burden of false positives (emotional stress, unnecessary biopsies) outweighing benefits. 1 The 2025 update strengthened this to a strong recommendation against routine use. 1

If You Must Order Cytology: How Many Specimens?

The literature does not specify an optimal number of cytology repetitions. 1 Historical practice involved single voided specimens for surveillance in established bladder cancer patients. 4, 5, 6

However, this question is moot because you should not be ordering cytology routinely in the first place. 1 The diagnostic accuracy does not improve sufficiently with multiple specimens to justify the practice when direct visualization via cystoscopy provides definitive assessment.

Special Consideration: Lynch Syndrome

For patients with personal or family history of Lynch syndrome, perform upper tract imaging regardless of risk category (CT or MR urography preferred), but cytology still remains non-routine. 1