Should urine cytology be performed on 3 different days to increase sensitivity in detecting abnormal cells?

Urine Cytology for Microhematuria Evaluation

Urine cytology should NOT be performed on 3 different days as it is not recommended as part of the routine evaluation of patients with microhematuria. 1

Evidence-Based Rationale

The 2025 American Urological Association (AUA) guidelines on microhematuria (MH) provide a strong recommendation against the routine use of urine cytology in the evaluation of patients with microhematuria:

• "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 MH." (Strong Recommendation; Evidence Level: Grade C) 1

• "Clinicians should not routinely use cytology or urine-based tumor markers as adjunctive tests in the setting of a normal cystoscopy." (Strong Recommendation; Evidence Level: Grade C) 1

Performance Characteristics of Urine Cytology

The DETECT I study, which included 3,556 patients with hematuria, found that urine cytology had:

• Sensitivity: 57.7%
• Specificity: 94.9%
• Positive predictive value: 35.7%
• Negative predictive value: 97.9% 1

Importantly, no bladder cancer or upper tract urothelial carcinoma (UTUC) was diagnosed based solely on a suspicious urinary cytology test. 1

Another study by Tan et al. (2019) confirmed these limitations, showing that urine cytology missed a significant number of muscle-invasive bladder cancers and high-risk disease. 2

Diagnostic Algorithm for Microhematuria

Instead of relying on urine cytology, the following approach is recommended:

1. Risk Stratification: Categorize patients into low/negligible-risk, intermediate-risk, or high-risk groups based on:

   • Age (women ≥50 years, men ≥40 years)
   • Smoking history
   • Degree of hematuria
   • Family history of urological malignancies
   • Occupational exposures 3

2. Initial Evaluation:

   • Complete urinalysis with microscopic examination
   • Renal and bladder ultrasound for all patients
   • Cystoscopy based on risk stratification 1

3. Imaging Selection:

   • Low/negligible-risk: Renal and bladder ultrasound
   • High-risk: CT urography (multi-phasic CT) 1, 3

Limited Role of Urine Cytology

Urine cytology may have a limited role in specific circumstances:

• Patients with persistent MH following a negative work-up
• Those with risk factors for carcinoma in situ (e.g., irritative voiding symptoms, tobacco use, chemical exposures) 1

However, even in these cases, collecting samples on three different days is not supported by evidence and would likely increase costs without improving diagnostic yield.

Follow-up Recommendations

For patients with persistent microhematuria after a negative initial evaluation:

• Low-risk: Cystoscopy at 3 months, 12 months, then annually for years 2-5 1
• Intermediate-risk: Cystoscopy and urine cytology at 3,6,9,12,18, and 24 months, then annually for years 3-5 1
• High-risk: Cystoscopy and urine cytology every 3 months initially, then every 6 months from years 3-5, then annually 1

Common Pitfalls to Avoid

1. Overreliance on urine cytology: The burden of emotional stress from false-positive results and risks of unnecessary diagnostic procedures outweigh potential benefits 1

2. Inadequate imaging: Using ultrasound alone in high-risk patients may miss significant pathology 3

3. Dismissing persistent microhematuria: Even with a negative initial evaluation, persistent microhematuria warrants follow-up 1, 3

4. Delays in evaluation: Delays >9 months in evaluating hematuria in patients with bladder cancer are associated with decreased survival 3

In conclusion, the current evidence strongly supports that urine cytology should not be routinely performed as part of microhematuria evaluation, and there is no evidence supporting collection on three different days.