Carver College of Medicine, University of Iowa, Iowa City.
Department of Urology, University of Iowa, Iowa City.
JAMA Netw Open. 2023 Feb 1;6(2):e230849. doi: 10.1001/jamanetworkopen.2023.0849.
Due to the ongoing bacillus Calmette-Guérin (BCG) shortage, sequential intravesical gemcitabine and docetaxel has been increasingly used as first-line therapy for high-risk non-muscle-invasive bladder cancer (NMIBC). However, data directly comparing these 2 therapies are lacking.
To compare the outcomes of patients with high-risk NMIBC treated with gemcitabine and docetaxel vs BCG.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted from January 1, 2011, to December 31, 2021. The median (IQR) duration of follow-up was 23 (12-33) months for patients receiving gemcitabine and docetaxel and 49 (27-79) months for patients receiving BCG. All patients were treated at the University of Iowa tertiary care center. A total of 312 patients with high-risk treatment-naive NMIBC were included; 174 patients were treated with BCG therapy and 138 were treated with gemcitabine and docetaxel therapy.
After undergoing complete transurethral resection of bladder tumor, patients received either sequential intravesical gemcitabine, 1 g, and docetaxel, 37.5 mg, or 1 vial of BCG. Induction treatments were administered once per week for 6 weeks. Maintenance regimens were initiated if the patient was disease free at the first follow-up visit.
The primary outcome was high-grade recurrence-free survival (RFS). Survival probabilities were estimated using the Kaplan-Meier method. Cox regression models were used to evaluate the association of covariates with outcomes. Adverse events were reported using the Common Terminology Criteria for Adverse Events, version 5.
Among 312 patients, the median (IQR) age was 73 (66-79) years; 255 patients (81.7%) were male and 292 (93.6%) were White. Baseline clinicopathological characteristics such as sex, smoking status, and pretreatment tumor pathology were similar between treatment groups. High-grade RFS estimates were 76% (95% CI, 69%-82%) at 6 months, 71% (95% CI, 64%-78%) at 12 months, and 69% (95% CI, 62%-76%) at 24 months in the BCG group and 92% (95% CI, 86%-95%) at 6 months, 85% (95% CI, 78%-91%) at 12 months, and 81% (95% CI, 72%-87%) at 24 months in the gemcitabine and docetaxel group. Multivariable Cox regression analyses controlled for age, sex, treatment year, and presence of carcinoma in situ revealed that treatment with gemcitabine and docetaxel was associated with better high-grade RFS (hazard ratio, 0.57; 95% CI, 0.33-0.97; P = .04) and RFS (hazard ratio, 0.56; 95% CI, 0.34-0.92; P = .02) than treatment with BCG. Induction therapy for BCG was associated with greater treatment discontinuation than induction therapy for gemcitabine and docetaxel (9.2% vs 2.9%; P = .02).
In this cohort study, gemcitabine and docetaxel therapy was associated with less high-grade disease recurrence and treatment discontinuation than BCG therapy. These findings suggest that, while awaiting results from an ongoing randomized clinical trial during the current BCG shortage, use of gemcitabine and docetaxel can be considered for recommendation in updated practice guidelines.
由于卡介苗（BCG）短缺，顺行膀胱内吉西他滨和多西他赛已越来越多地被用作高危非肌肉浸润性膀胱癌（NMIBC）的一线治疗方法。然而，直接比较这两种治疗方法的数据尚缺乏。
比较高危 NMIBC 患者接受吉西他滨和多西他赛与 BCG 治疗的结果。
设计、设置和参与者：本回顾性队列研究于 2011 年 1 月 1 日至 2021 年 12 月 31 日进行。吉西他滨和多西他赛组患者的中位（IQR）随访时间为 23（12-33）个月，BCG 组患者的中位（IQR）随访时间为 49（27-79）个月。所有患者均在爱荷华大学三级医疗中心接受治疗。共纳入 312 例高危初治 NMIBC 患者；174 例患者接受 BCG 治疗，138 例患者接受吉西他滨和多西他赛治疗。
在完全经尿道膀胱肿瘤切除术（TURBT）后，患者接受了顺行膀胱内吉西他滨 1 g 和多西他赛 37.5 mg 治疗，或 1 瓶 BCG 治疗。诱导治疗每周进行 1 次，共进行 6 周。如果患者在首次随访时无疾病，则开始维持治疗。
主要结局是高级别无复发生存率（RFS）。采用 Kaplan-Meier 法估计生存率。采用 Cox 回归模型评估协变量与结局的关系。采用不良事件通用术语标准（CTCAE）第五版报告不良事件。
在 312 例患者中，中位（IQR）年龄为 73（66-79）岁；255 例（81.7%）患者为男性，292 例（93.6%）为白人。治疗组之间的基线临床病理特征（如性别、吸烟状况和术前肿瘤病理）相似。BCG 组的高级别 RFS 估计值分别为 6 个月时 76%（95%CI，69%-82%）、12 个月时 71%（95%CI，64%-78%）、24 个月时 69%（95%CI，62%-76%），吉西他滨和多西他赛组的 6 个月时 92%（95%CI，86%-95%）、12 个月时 85%（95%CI，78%-91%）、24 个月时 81%（95%CI，72%-87%）。多变量 Cox 回归分析控制了年龄、性别、治疗年份和原位癌的存在，结果显示，与 BCG 治疗相比，吉西他滨和多西他赛治疗与更好的高级别 RFS（风险比，0.57；95%CI，0.33-0.97；P=0.04）和 RFS（风险比，0.56；95%CI，0.34-0.92；P=0.02）相关。BCG 诱导治疗的停药率高于吉西他滨和多西他赛诱导治疗（9.2%比 2.9%；P=0.02）。
在本队列研究中，吉西他滨和多西他赛治疗与 BCG 治疗相比，高级别疾病复发和停药率较低。这些发现表明，在卡介苗短缺期间等待正在进行的随机临床试验结果的同时，可以考虑在更新的实践指南中推荐使用吉西他滨和多西他赛。
