What does positive cytology in a follow-up case of Transurethral Resection of Bladder Tumor (TURBT) indicate?

Positive Cytology in Follow-up TURBT: Significance and Management

Positive urinary cytology in a follow-up case of TURBT indicates the presence of urothelial tumor cells anywhere in the urinary tract, suggesting potential recurrence or residual disease that requires comprehensive evaluation even when cystoscopy appears normal.

Significance of Positive Cytology

• Positive urinary cytology after TURBT is a significant finding that may indicate urothelial tumor anywhere in the urinary tract, including the bladder, upper urinary tract, or prostatic urethra in men 1
• It serves as an independent prognostic factor for cancer recurrence, with studies showing that patients with positive cytology have significantly higher 5-year cumulative progression rates (20%) compared to those with negative cytology (2%) 2
• Positive cytology may indicate the fragility of intercellular adhesion of bladder cancer cells, a critical biological process for invasion and metastasis 2

Diagnostic Implications

• Positive cytology with normal cystoscopy findings requires thorough evaluation to locate the source of malignant cells 1, 3
• In patients with positive cytology after TURBT, the recurrence rate is significantly higher (72.3%) compared to those with negative cytology (30.6%) 4
• Positive cytology outperforms histological grade as a prognostic predictor for progression and cancer-specific mortality in non-muscle invasive bladder cancer 2

Required Evaluation

When positive cytology is found in follow-up with normal cystoscopy:

1. Bladder Evaluation:

   • Transurethral resection with directed or selected mapping biopsies of the bladder must be performed 1, 3
   • Random biopsies of normal-appearing urothelium should be considered to detect carcinoma in situ (CIS) 3

2. Upper Tract Evaluation:

   • Complete assessment of the upper urinary tract is mandatory 1
   • Options include CT urography, intravenous pyelogram, retrograde pyelogram, renal ultrasound, or MRI urogram 1, 3
   • Ureteroscopy may be considered for direct visualization of the upper tract 3

3. Prostate Evaluation (in men):

   • Transurethral resection biopsy of the prostate should be performed to rule out urothelial involvement of the prostatic urethra 1, 3

Management Based on Evaluation Results

• If bladder mapping biopsies are positive:

  • Intravesical BCG treatment followed by maintenance BCG (if complete response is seen) is recommended 1, 3
  • For tumors that fail to respond to BCG, options include cystectomy or changing the intravesical agent 1

• If TUR biopsy of the prostate is positive:

  • Treatment should follow protocols for urothelial carcinomas of the prostate 1

• If upper tract evaluation is positive:

  • Treatment should follow protocols for upper genitourinary tract tumors 1

• If all evaluations are negative:

  • Close follow-up at 3-month intervals is recommended 1
  • Maintenance therapy with BCG is optional 1

Prognostic Value

• Positive cytology after TURBT is associated with higher tumor stage, grade, size, and multiplicity 4
• It serves as an independent risk factor for progression and cancer-specific mortality in both time-fixed and time-dependent models 2
• In patients with immediate post-TURBT positive cytology, there is a significantly higher risk of recurrence (HR 1.83) 4

Follow-up Recommendations

• For high-risk non-muscle invasive bladder cancer, follow-up should include urinary cytology and cystoscopy at 3- to 6-month intervals for the first 2 years 3
• Imaging of the upper tract should be considered every 1-2 years for high-risk tumors 3
• Combined negative cytology and cystoscopy after BCG induction has a high negative predictive value (98%) for residual tumor 5

Common Pitfalls and Caveats

• Relying solely on cystoscopy without cytology may miss recurrences, especially CIS which can appear as normal mucosa 1
• Ignoring positive cytology when cystoscopy is normal is a serious error, as it may indicate tumor in areas not visible during cystoscopy 1
• Failing to evaluate the upper tract and prostate when cytology is positive but cystoscopy is normal can miss significant disease 3
• Cost-effectiveness of routine cytology has been questioned, suggesting its application should be tailored to individual risk profiles 6