Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 224, Baltimore, MD, 21287, USA.
Department of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
World J Urol. 2019 Oct;37(10):2051-2058. doi: 10.1007/s00345-018-02624-3. Epub 2019 Jan 23.
Urine cytology remains an essential diagnostic tool in the surveillance of patients with non-muscle invasive bladder cancer (NMIBC). The correlation of urine cytology with biopsy specimens to determine its accuracy following induction intravesical therapy has not been investigated.
A retrospective review was performed of patients who underwent intravesical therapy for biopsy-proven non-muscle invasive disease between 2013 and 2016 at our institution. All patients uniformly underwent cytology and systematic bladder biopsies in the operating room within 12 weeks following intravesical therapy. The accuracy of urinary cytology in predicting high-grade disease recurrence following intravesical therapy was confirmed by correlating cytology results to post-treatment systematic biopsies, regardless of endoscopic findings. Only patients with complete information regarding urine cytology and pathologic biopsy results, both pre- and post-intravesical therapy, were included.
90 cytology samples following intravesical therapy were analyzed from 76 patients who met inclusion criteria. 72 (80.0%) and 18 (20.0%) of the samples were collected from patients initially treated for high- and low-grade disease, respectively. Fifty-six (62.2%) specimens were obtained from patients following induction of bacillus Calmette-Guerin (BCG) therapy; the remainder were from patients treated with intravesical gemcitabine/docetaxel, mitomycin, or BCG/interferon. For patients treated with BCG, cytology was positive for high-grade disease in 8/15 patients with high-grade pathology on follow-up biopsy, thus demonstrating a sensitivity of 53% (95% CI 27-79%), specificity of 95% (95% CI 84-99%), positive predictive value of 80% (95% CI 44-98%), and negative predictive value of 85% (95% CI 71-94%). If cytologic interpretation was broadened to include high-grade and "suspicious for high-grade" findings, sensitivity increased to 67% (95% CI 38-88%) and specificity decreased to 88% (95% CI 74-96%).
While urinary cytology maintains a high specificity following intravesical therapy, it demonstrates a low sensitivity for potentially aggressive high-grade urothelial carcinoma. Further evaluation of more effective, clinic-based enhanced cystoscopy techniques and biomarkers is warranted to better identify patients at risk for disease recurrence following BCG therapy.
尿液细胞学仍然是监测非肌肉浸润性膀胱癌（NMIBC）患者的重要诊断工具。在诱导膀胱内治疗后，尿液细胞学与活检标本的相关性以确定其准确性尚未得到研究。
对 2013 年至 2016 年间在我院接受膀胱内治疗的活检证实为非肌肉浸润性疾病的患者进行了回顾性分析。所有患者在膀胱内治疗后 12 周内均在手术室接受细胞学和系统膀胱活检。通过将细胞学结果与治疗后系统活检相关联，无论内镜检查结果如何，均证实了尿液细胞学在预测膀胱内治疗后高级别疾病复发方面的准确性。仅包括具有完整的尿液细胞学和病理活检结果信息的患者，包括膀胱内治疗前后的信息。
从符合纳入标准的 76 名患者中分析了 90 例膀胱内治疗后的细胞学样本。样本中分别有 72 例（80.0%）和 18 例（20.0%）来自最初接受高级别和低级别疾病治疗的患者。56 例（62.2%）标本取自接受卡介苗（BCG）诱导治疗的患者；其余标本取自接受膀胱内吉西他滨/多西他赛、丝裂霉素、BCG/干扰素治疗的患者。对于接受 BCG 治疗的患者，细胞学检查对高级别疾病呈阳性，在随访活检中有 15 例高级别病理学患者，因此灵敏度为 53%（95%CI 27-79%），特异性为 95%（95%CI 84-99%），阳性预测值为 80%（95%CI 44-98%），阴性预测值为 85%（95%CI 71-94%）。如果细胞学解释扩大到包括高级别和“高级别可疑”发现，则灵敏度增加至 67%（95%CI 38-88%），特异性降低至 88%（95%CI 74-96%）。
尽管在膀胱内治疗后尿液细胞学仍具有较高的特异性，但对于潜在侵袭性高级别尿路上皮癌，其灵敏度较低。需要进一步评估更有效的基于临床的增强膀胱镜技术和生物标志物，以更好地识别接受 BCG 治疗后有疾病复发风险的患者。
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