Department of Urology, Mayo Clinic Arizona, Phoenix, AZ.
Department of Urology, Mayo Clinic Arizona, Phoenix, AZ.
Urol Oncol. 2024 Jan;42(1):21.e21-21.e28. doi: 10.1016/j.urolonc.2023.09.010. Epub 2023 Oct 16.
Bacillus Calmette-Guerin (BCG) is the most effective therapy available to treat high-risk nonmuscle invasive bladder cancer (NMIBC) patients. However, for patients with immunomodulating conditions BCG is a relative contraindication due to efficacy and safety concerns. To our knowledge, no population-level study evaluating the efficacy and safety profile of BCG for immunomodulated patients exists.
NMIBC patients aged 66 years or older were identified in the Surveillance, Epidemiology, and End Results (SEER) - Medicare database from 1975-2013. All patients completed adequate BCG (at least 5 plus 2 treatments completed within 12 months of diagnosis). Two groups were defined: an immunomodulated population identified by immunomodulating conditions such as solid-organ transplantation, HIV, and autoimmune conditions, and an immunocompetent group. The primary endpoint was 5-year progression-free survival defined as progression to systemic chemotherapy, checkpoint inhibitors, radical or partial cystectomy, metastasis, or cancer-specific death. A safety analysis was performed as a secondary outcome.
In a total of 4,277 patients with NMIBC who completed adequate BCG, 606 (14.2%) were immunomodulated. The immunomodulated group was older at diagnosis (P < 0.001), more likely to be female (P < 0.001), more likely to live in a metropolitan area (P < 0.001), and had higher Charlson comorbidity scores (P < 0.001). There were no differences in progression to chemotherapy (P = 0.17), checkpoint inhibitors (P > 0.99), radical cystectomy (P = 0.40), partial cystectomy (P = 0.93), metastasis (P = 0.19), cancer-specific death (P = 0.18) or 5-year total bladder cancer progression (P = 0.30) between the groups. For the safety analysis, rates of disseminated BCG were similar between immunomodulated and immunocompetent patients (0.7% vs. <1.8%, P = 0.51). On multivariable analysis 5-year total bladder cancer progression (HR 1.07 [CI 0.88-1.30]) was similar between the groups.
Rates of bladder cancer progression and disseminated BCG complications 5-years after BCG therapy were similar regardless of immunomodulation status. These findings suggest that BCG intravesical therapy can be offered to immunomodulated patients with high-risk NMIBC although theoretical infectious complication risks remain.
卡介苗（BCG）是治疗高危非肌肉浸润性膀胱癌（NMIBC）患者的最有效疗法。然而，对于有免疫调节状况的患者，由于疗效和安全性问题，BCG 是相对禁忌证。据我们所知，目前尚无评估免疫调节患者使用 BCG 的疗效和安全性的人群水平研究。
我们在 1975 年至 2013 年间从监测、流行病学和最终结果（SEER）-医疗保险数据库中确定了年龄在 66 岁或以上的 NMIBC 患者。所有患者均完成了足够的 BCG（至少完成了 5 次治疗，且在诊断后 12 个月内完成了 2 次治疗）。将患者分为两组：一组是免疫调节人群，包括实体器官移植、HIV 和自身免疫性疾病等免疫调节状况；另一组是免疫功能正常人群。主要终点是 5 年无进展生存率，定义为进展为全身化疗、检查点抑制剂、根治性或部分膀胱切除术、转移或癌症特异性死亡。作为次要结果进行了安全性分析。
在 4277 名完成足够 BCG 治疗的 NMIBC 患者中，有 606 名（14.2%）为免疫调节患者。免疫调节组的诊断年龄更大（P < 0.001），女性患者更多（P < 0.001），居住在大都市地区的患者更多（P < 0.001），Charlson 合并症评分更高（P < 0.001）。两组之间化疗进展（P = 0.17）、检查点抑制剂（P > 0.99）、根治性膀胱切除术（P = 0.40）、部分膀胱切除术（P = 0.93）、转移（P = 0.19）、癌症特异性死亡（P = 0.18）或 5 年总膀胱癌进展（P = 0.30）均无差异。对于安全性分析，免疫调节和免疫功能正常患者的播散性 BCG 发生率相似（0.7% vs. <1.8%，P = 0.51）。多变量分析显示，两组 5 年总膀胱癌进展（HR 1.07 [CI 0.88-1.30]）相似。
BCG 治疗 5 年后膀胱癌进展和播散性 BCG 并发症的发生率在免疫调节状态不同的情况下相似。这些发现表明，尽管存在理论上的感染并发症风险，但可以向高危 NMIBC 的免疫调节患者提供 BCG 膀胱内治疗。
