Efficacy of neoadjuvant chemotherapy and combined immunotherapy in muscle-invasive bladder cancer: a single-center real-world retrospective study
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摘要: 目的 探讨膀胱癌化疗联合免疫治疗的新辅助方案治疗肌层浸润性膀胱癌(muscle-invasive bladder cancer，MIBC)患者的疗效和安全性。方法 收集分析2018年1月—2023年3月南京医科大学第一附属医院泌尿外科收治的共56例MIBC患者的临床资料。根据新辅助治疗方案的不同将患者分为化疗组(34例)与联合组(22例)，化疗组使用吉西他滨联合顺铂新辅助化疗，联合组在此化疗基础上加用免疫检查点抑制剂替雷利珠单抗200 mg或特瑞普利单抗240 mg。比较2组患者的病理降期率、病理完全缓解率及中短期不良反应发生率等相关指标。结果 联合组中12例(54.5%)患者获得了病理完全缓解(ypT0)、5例(22.7%)患者部分缓解(ypT1/Ta/Tis)，病理降期率为77.3%，病理完全缓解率为54.5%；化疗组中8例(23.5%)患者获得了病理完全缓解、6例(17.6%)患者部分缓解，病理降期率为41.2%，病理完全缓解率为23.5%；2组比较差异有统计学意义(P < 0.05)。联合组亚组间的病理降期率及病理完全缓解率差异无统计学意义(P>0.05)。2组患者均未发生严重过敏反应和导致患者死亡的严重不良事件，未出现4级不良事件。联合组3级不良事件发生率高于化疗组(45.6% vs 35.3%)，但差异无统计学意义(P>0.05)。结论 吉西他滨、顺铂化疗联合免疫治疗的新辅助治疗方案可明显提高患者的病理降期率和病理完全缓解率，且不明显增加中短期3级不良事件发生率。Abstract: Objective To investigate the efficacy and safety of the neoadjuvant regimen of bladder cancer chemotherapy combined with immunotherapy in the treatment of patients with muscle-invasive bladder cancer(MIBC).Methods Clinical data of a total of 56 MIBC patients admitted to First Affiliated Hospital of Nanjing Medical University were collected and analyzed. The patients were divided into two groups according to the different neoadjuvant treatment regimens; the chemotherapy group used gemcitabine combined with cisplatin, and the combination group added an immune checkpoint blocker on the basis of this chemotherapy. The pathological downstage rate, pathological complete remission rate and short-to-medium term adverse reaction rate and other related indexes of the two groups were compared.Results In the combination group, 12 patients achieved pathological complete remission(ypT0)(54.5%), 5 patients(22.7%) partial remission(ypT1), with a pathological downstaging rate of 77.3% and a pathological complete remission rate of 54.5%, whereas in the chemotherapy group, 8 patients(23.5%) achieved complete remission, 6 patients(17.6%) partial remission, with a pathological downstaging rate of 41.2%, and the pathological complete remission rate was 23.5%, with statistical differences between the two groups(P < 0.05), There was no statistically significant difference in the rate of pathological downstaging or pathological complete remission between subgroups of the combined group(P>0.05). No serious allergic reactions or adverse events leading to patient's death occurred in the two groups, and there were no grade 4 adverse events. The rate of grade 3 adverse events in the combination group was 45.6%, higher than that in the chemotherapy group(35.3%), but there was no statistically significant difference(P>0.05).Conclusion The neoadjuvant chemotherapy regimen of gemcitabine and cisplatin chemotherapy combined with immunotherapy can significantly increase the pathological downstage rate and pathological complete remission rate of patients, but does not significantly increase the incidence of short-to-medium term grade 3 adverse events, which can be safely applied.
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表 1 联合组和化疗组患者一般资料比较
例(%)，X±S 一般资料 联合组
(22例)化疗组
(34例)P值 年龄/岁 68.6±9.2 63.97±9.23 0.07 性别 0.66 男 21(95.5) 30(88.2) 女 1(4.5) 4(11.8) 术前诊断 0.53 诊断性电切 8(36.4) 6(17.6) 活检 14(63.6) 28(82.4) BMI/(kg/m2) 24.47±2.11 23.58±3.69 0.26 吸烟史 13(59.1) 17(50.0) 0.51 ECOG评分 0.18 0~1分 12(54.5) 12(35.3) 2~3分 10(45.5) 22(64.7) 组织学分级 0.19 高级别 22(100.0) 29(85.3) 低级别 0(0) 5(14.7) 术前T分期 0.65 cT2 6(27.2) 14(41.2) cT3 8(36.4) 10(29.4) cT4a 8(36.4) 10(29.4) 术前N分期 0.97 N0 20(91.0) 31(91.2) N+ 2(9.0) 3(8.8) 手术方式 0.55 RC+回肠代膀胱术 16(72.7) 26(76.5) RC+输尿管皮肤造
口术4(18.2) 8(23.5) TURBT 2(9.1) 0(0) 
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表 2 联合组与化疗组病理降期率比较
例(%) 指标 联合组
(22例)化疗组
(34例)P值 病理反应结局 0.02 ypT0 12(54.5) 8(23.5) ypT1 5(22.7) 6(17.6) ≥ypT2 5(22.7) 20(58.8) pCR率 12(54.5) 8(23.5) 0.02 病理降期率 17(77.3) 14(41.2) 0.01
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表 3 联合组亚组病理降期率比较
例(%) 指标 GC+替雷利珠单抗(12例) GC+特瑞普利单抗(10例) P值 ypT0 7(58.3) 5(50.0) 0.857 ypT1 3(25.0) 2(20.0) ≥ypT2 2(16.7) 3(30.0) pCR 7(58.3) 5(50.0) 0.857 病理降期 10(83.3) 7(70.0) 0.816
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表 4 联合组与化疗组不良事件率比较
例(%) 不良事件 联合组(22例) 化疗组(34例) P值 1~2级 3级 1~2级 3级 皮疹 2(9.1) 0(0) 3(8.8) 0(0) 胃肠道反应 9(40.9) 2(9.1) 12(35.3) 3(8.8) 肝肾功能损害 1(4.5) 2(9.1) 1(2.9) 4(11.8) 血液系统损害 4(18.2) 4(18.2) 13(38.3) 5(14.7) 内分泌系统损害 0(0) 2(9.1) 0(0) 0(0) 1~2级不良反应率 16(72.7) 29(85.3) 0.83 3级不良反应率 10(45.5) 12(35.3) 0.45
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