Bladder Biopsy of Normal-Appearing Mucosa is Not Helpful in Patients with Unexplained Positive Cytology after Nonmuscle Invasive Bladder Cancer

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Malignant voided cytology with normal endoscopic evaluation represents a diagnostic and therapeutic challenge in many patients with a history of nonmuscle invasive bladder cancer. Bladder biopsy is often advised but its efficacy is unclear. We evaluated the usefulness of bladder biopsy in patients with unexplained positive cytology and describe recurrence patterns in this unique patient subset.

Materials and Methods:

From an institutional database we retrospectively identified patients with a history of nonmuscle invasive bladder cancer and surveillance cystoscopy from 2008 to 2012 who had malignant voided urine cytology but normal cystoscopy. Patients underwent systematic bladder biopsy or cystoscopic surveillance and were followed for recurrence and progression.


Of 444 patients 343 were followed with surveillance only and 101 underwent a total of 118 biopsies of normal-appearing bladder mucosa. Three biopsies (2.5%) showed carcinoma in situ and none revealed invasive carcinoma. During the median 32-month followup recurrence developed in the bladder in 194 patients (44%), in the upper tract in 24 (5%) and in the prostatic urethra in 5 (1%) while 219 (49%) had no recurrence. A previous diagnosis of upper tract urothelial carcinoma and a history of bacillus Calmette-Guérin treatment were associated with an increased recurrence risk on multivariate analysis. Recurrence rates and patterns were similar in the biopsy and surveillance groups.


Patients with malignant cytology despite normal cystoscopy have a high recurrence rate. Biopsy of normal-appearing bladder mucosa in this setting is rarely positive and does not alter the recurrence pattern.

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