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Hermans, Julian; Jokisch, Friedrich; Volz, Yannic; Eismann, Lennert; Pfitzinger, Paulo; Ebner, Benedikt; Weinhold, Philipp; Schlenker, Boris; Stief, Christian G.; Tritschler, Stefan und Schulz, Gerald B. (2021): Impact of bacillus Calmette-Guerin intravesical therapy on the diagnostic efficacy of The Paris System for Reporting Urinary Cytology in patients with high-grade bladder cancer. In: Cancer Cytopathology, Bd. 130, Nr. 4: S. 294-302

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Abstract

Background In high-grade urothelial carcinoma (UC) of the bladder, bacillus Calmette-Guerin (BCG) therapy is a therapeutic mainstay, and urinary cytology is recommended to detect recurrences. However, intravesical BCG instillations can induce morphologic changes in urothelial cells. The authors investigated the impact of BCG therapy on the efficacy of urinary cytology. Methods Matched pathology and cytology samples from patients undergoing transurethral resection of the bladder after BCG therapy were assessed. Cytology samples were graded according to The Paris System for Reporting Urinary Cytology. Diagnostic quality criteria were tested for different cutoff definitions, and the results were compared between those obtained <100 versus >= 100 days after the last BCG instillation. In addition, the oncologic outcome of false-positive results was assessed. Results In total, 389 matched cases from 197 patients who had a history of high-grade UC (HGUC) were identified. Sixty cases (15.7%) were diagnosed as high-grade urothelial bladder cancer. The cytology diagnoses were as follows: non-HGUC, 191 cases (49.1%);atypical urothelial cells, 80 cases (20.6%);suspicious for HGUC, 56 cases (14.4%);and HGUC, 56 cases (14.4%). Interrater reliability was substantial (kappa = 0.660). Sensitivity increased from 45% to 75% when cases diagnosed as suspicious for HGUC were also counted as positive. Notably, sensitivity was reduced within the first 100 days after BCG therapy (61.9%) compared with sensitivity at longer intervals (82.1%). Reactive atypia (odds ratio, 4.155;95% confidence interval, 2.136-8.085;P < .001) and cellular degeneration (odds ratio, 5.050;95% CI, 2.094-12.175;P < .001) of urothelial cells were associated with false-positive rates, and 44.7% of patients who had a false-positive cytology classification presented with HGUC during follow-up. Conclusions BCG therapy has a short-term adverse impact on the efficacy of urinary cytology. After BCG therapy, cases classified as suspicious for HGUC should be considered positive. Importantly, patients with false-positive cytology findings should be closely monitored.

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