Department of Surgical Oncology (Urology), Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Department of Surgical Oncology (Urology), Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Urol Oncol. 2022 Jul;40(7):346.e9-346.e16. doi: 10.1016/j.urolonc.2022.02.021. Epub 2022 Apr 4.
Urine cytology and cystoscopy are routinely employed during follow-up of patients after trimodal therapy (TMT) for muscle-invasive bladder cancer (MIBC). The significance of positive or equivocal cytology without visible disease recurrence on cystoscopy during follow-up is unknown, and studies informing outcomes in this scenario are lacking. This study aims to investigate the temporal trends of positive/equivocal cytology in the absence of visible disease recurrence and the association with bladder cancer recurrence and survival outcomes.
One hundred and twenty-nine patients with available post-TMT cytology data and negative cystoscopy from a single academic institution between 2002 and 2017 with a median follow-up of 3.4 (range 0.1-14.2) years were analyzed. Cytology results, first post-TMT cytology positive/equivocal (CP) and negative (CN), were evaluated for association with disease recurrence and survival. Kaplan. Meier and competing risks methods were used to assess time-to-negative cytology in CP patients with ≥2 interval post-TMT cytology results (n = 33), time-to-recurrence, and disease-specific mortality (DSM) stratified by first post-TMT cytology result.
At first follow-up (6-8 weeks post-TMT completion), CP was observed in 41 (32%) and CN in 88 (68%) of patients. With further follow-up of CP patients with ≥2 interval post-TMT cytology results, the probability of developing negative cytology was 57% (95% CI 42, 77) at 6 months post-TMT, and the median time-to-negative cytology was 3.2 months (95% CI 2.99, 5.80). The median time-to-recurrence was reduced in CP patients compared to CN (24.3 vs. 78.1 months, p = 0.1), corresponding with an apparent increase in the cumulative incidence of recurrence rate at 3 years in the CP vs. CN group (62% vs. 42%, p = 0.1). No significant difference was observed in the 3-year DSM rates. On univariable analysis, the hazards of recurrence and DSM for patients with CP were 1.5 (95% CI 0.9, 2.5, p = 0.1) and 2.1 (95% CI 0.9, 4.7, p = 0.07) respectively.
This is the first study to investigate the significance of a positive/equivocal cytology without visible disease following TMT for MIBC. Positive cytology is common and does not preclude subsequent negative cytology supporting a watchful waiting approach rather than proceeding immediately to biopsy. However, cytology that remains positive at subsequent follow-up may be associated with adverse recurrence and survival outcomes.
在肌层浸润性膀胱癌（MIBC）患者接受三联疗法（TMT）后进行随访时，常规进行尿液细胞学检查和膀胱镜检查。在随访期间，膀胱镜检查未见疾病复发但细胞学检查为阳性或不确定意义时的意义尚不清楚，且缺乏此类情况下的结局研究。本研究旨在探讨在无可见疾病复发的情况下细胞学检查阳性/不确定意义的时间趋势，以及与膀胱癌复发和生存结局的关系。
对 2002 年至 2017 年间，在单一学术机构接受 TMT 后有可用细胞学检查数据且膀胱镜检查阴性的 129 例患者进行分析，中位随访时间为 3.4 年（范围 0.1-14.2 年）。评估细胞学检查结果、首次 TMT 后阳性/不确定意义的细胞学检查（CP）和阴性细胞学检查（CN）与疾病复发和生存的关系。Kaplan-Meier 和竞争风险方法用于评估≥2 次 TMT 后间隔细胞学检查结果（n=33）的 CP 患者的阴性细胞学检查时间、复发时间和疾病特异性死亡率（DSM），并根据首次 TMT 后细胞学检查结果分层。
在第一次随访（TMT 完成后 6-8 周）时，41 例（32%）患者的 CP 为阳性，88 例（68%）患者的 CN 为阴性。在对 CP 患者进行进一步随访，且随访期间有≥2 次间隔的 TMT 后细胞学检查结果时，CP 患者出现阴性细胞学检查的概率为 6 个月时 57%（95%CI 42,77），阴性细胞学检查的中位时间为 3.2 个月（95%CI 2.99,5.80）。与 CN 组相比，CP 组的复发中位时间缩短（24.3 个月 vs. 78.1 个月，p=0.1），CP 组在 3 年时的累积复发率明显高于 CN 组（62% vs. 42%，p=0.1）。CP 组和 CN 组 3 年的 DSM 率无显著差异。单变量分析显示，CP 患者的复发和 DSM 的风险比分别为 1.5（95%CI 0.9,2.5，p=0.1）和 2.1（95%CI 0.9,4.7，p=0.07）。
这是第一项研究肌层浸润性膀胱癌患者接受 TMT 治疗后，细胞学检查阳性/不确定意义而无可见疾病时的意义。CP 较为常见，但并不排除随后出现阴性细胞学检查，支持观察等待方法，而不是立即进行活检。然而，在后续随访中持续呈阳性的细胞学检查可能与不良的复发和生存结局相关。
