肌层浸润性膀胱癌新辅助化疗病理与长期临床结局——单中心15年真实世界临床研究

张瑞赟; 金迪; 钱雷; 阿克周力; 夏骏; 曹明; 张连华; 薛蔚; 黄翼然; 陈海戈

doi:10.13201/j.issn.1001-1420.2023.12.005

肌层浸润性膀胱癌新辅助化疗病理与长期临床结局——单中心15年真实世界临床研究

- 1.
  上海交通大学医学院附属仁济医院泌尿科(上海，200127)
- 2.
  上海交通大学医学院附属仁济医院病理科
基金项目:
国家自然科学基金(No：81672514，81902562)；上海市科委基金项目(No：16ZR1420300，18410720400，19431907400)；上海交通大学医学院基金(No：TM201708)；上海交通大学医学院附属仁济医院临床科研创新培育基金(No：RJZZ18-020，PYIII-17-017，PY2018-IIC-02)；上海申康医院发展中心项目(No：SHDC12015125)

详细信息

通讯作者: 陈海戈，E-mail：rjbladder@163.com

中图分类号: R737.14

收稿日期: 2023-10-23

刊出日期: 2023-12-06

Pathologic and long-term outcomes of neoadjuvant chemotherapy for muscle-invasive bladder cancer: a single-center, 15-year real-world study

- 1.
  Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
- 2.
  Department of Pathology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine

More Information

Corresponding author: CHEN Haige, E-mail: rjbladder@163.com

Received Date: 23 October 2023

Publish Date: 06 December 2023

摘要

摘要: 目的报道吉西他滨联合顺铂(GC)方案新辅助化疗联合全膀胱切除术治疗肌层浸润性膀胱癌(muscle-invasive bladder cancer，MIBC)的病理学与长期生存数据。方法纳入2003—2017年上海交通大学医学院附属仁济医院临床诊断为MIBC、临床分期为cT_2~4NanyM₀，并行根治性全膀胱切除术的1 220例患者进行回顾性分析。按照患者术前是否接受新辅助化疗，分为单纯全膀胱组(RC组，783例)与新辅助联合全膀胱组(NAC组，437例)。对2组的队列特征、总生存期(overall survival，OS)，肿瘤特异性生存期(cancer specific survival，CSS)、无复发生存期(recurrence free survival，RFS)、病理缓解率等进行比较。结果 NAC组患者的年龄与RC组相比显著降低；临床分期方面，RC组cT_4a期患者比例高于NAC组(10.7% vs 5.7%，P=0.012)，但2组cN分期比较差异无统计学意义(P=0.153)。NAC组达到完全病理缓解(complete pathological response，ypCR)的患者共99例(22.6%)，达到部分病理缓解(partial pathological response，ypPR)的患者共142例(32.5%)，总病理缓解(overall pathological response rate，ypRR)共241例(55.1%)。NAC组5年OS、CSS、RFS率分别为74.4%、76.6%、71.3%，10年OS、CSS、RFS率分别为48.1%、62.5%、55.7%，平均OS、CSS、RFS分别为97.6、108.6、99.2个月。RC组5年OS、CSS、RFS率分别为58.6%、64.1%、54.8%，10年OS、CSS、RFS率分别为46.9%、56.0%、32.7%，平均OS、CSS、RFS分别为89.6、97.5、83.2个月。经倾向性评分匹配后，NAC组的平均OS(P＜0.001)、平均CSS(P＜0.001)以及平均RFS(P＜0.001)均显著优于RC组。结论 GC方案新辅助化疗可以显著改善MIBC患者的预后，使肿瘤通过化疗达到病理降期，延长OS、CSS、RFS。
- 膀胱癌 /
- 新辅助化疗 /
- 预后 /
- 长期随访
Abstract: Objective To assess the value of gemcitabine plus cisplatin(GC) neoadjuvant chemotherapy with radical cystectomy in the treatment of patients with muscle-invasive bladder cancer(MIBC).Methods This study included a retrospective analysis of a total of 1 220 cases diagnosed as MIBC(cT_2-4NanyM₀) in Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine from 2003 to 2017. According to whether received neoadjuvant chemotherapy before surgery, all patients were divided into a radical cystectomy group(RC group) and a neoadjuvant chemotherapy group(NAC group), and there were 783 cases in RC group and 437 cases in NAC group. The cohort characteristics, overall survival(OS), cancer specific survival(CSS), recurrence free survival(RFS), and pathological downstage rate of the two groups were compared.Results The age of patients in the NAC group was significantly younger than that in the RC group; In terms of clinical stage, the proportion of patients in the RC group with cT_4a was higher than that in the NAC group(10.7% vs 5.7%, P=0.012), but no significant difference was found between the two groups in the cN stage(P=0.153). In the NAC group, 99 cases(22.6%) were found complete pathological response (ypCR), 142 cases(32.5%) were found ypPR and 241(55.1%) cases were found ypRR. In the NAC group, the 5-year OS, CSS, and RFS rates were 74.4%, 76.6%, and 71.3% respectively, the 10-year OS, CSS, and RFS rates were 48.1%, 62.5%, and 55.7% respectively, and the average duration of OS, CSS, and RFS were 97.6, 108.6, and 99.2 months. In the RC group, the 5-year OS, CSS, and RFS rates respectively were 58.6%, 64.1%, and 54.8%, the 10-year OS, CSS, and RFS rates were 46.9%, 56.0%, and 32.7%, and the average duration of OS, CSS, and RFS were 89.6, 97.5, and 83.2 months. After propensity score matching, NAC group was significantly better than the RC group in average OS(P=0.001), average CSS(P < 0.001), and average RFS(P < 0.001).Conclusion GC neoadjuvant chemotherapy can improve survival of the patients with MIBC, facilitate tumor downstage and increase the overall survival duration, the recurrence free survival duration and cancer specific survival duration.
- bladder cancer /
- neoadjuvant chemotherapy /
- prognosis /
- long-term follow-up

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图 1 研究队列流程图

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图 2 PSM后NAC组与RC组OS、CSS与RFS的Kaplan-Meier曲线

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图 3 获得ypCR、ypPR与无病理学缓解的NAC亚组OS、CSS与RFS的Kaplan-Meier曲线

下载: 全尺寸图片幻灯片

表 1 研究队列临床病理参数比较例(%)，X±S

临床参数	RC组(783例)	NAC组(437例)	P值
男性	650(83.0)	340(77.8)	0.031
年龄/岁	67.4±7.7	62.7±10.0	＜0.001
临床T分期			0.012
cT₂	548(70.0)	319(73.0)
cT₃	151(19.3)	93(21.3)
cT_4a	84(10.7)	25(5.7)
临床N分期			0.153
cTanyN₀	659(84.2)	381(87.2)
cTanyN_1~3	124(15.8)	56(12.8)
手术方式			0.788
开放	219(28.0)	128(29.3)
腹腔镜	308(39.3)	174(39.8)
机器人	256(32.7)	135(30.9)
病理T分期			＜0.001
pT₀	56(7.2)	108(24.7)
pT_a	9(1.1)	19(4.3)
pT₁	111(14.2)	107(24.5)
pTis	20(2.6)	25(5.7)
pT₂	214(27.3)	56(12.8)
pT₃	266(34.0)	98(22.4)
pT₄	107(13.7)	24(5.5)
病理N分期^a)			0.012
pTanyN₀	498(80.6)	364(87.9)
pTanyN₁	66(10.7)	28(6.8)
pTanyN₂	39(6.3)	13(3.1)
pTanyN₃	15(2.4)	9(2.2)
合并原位癌	94(12.0)	52(11.9)	1.000
LVI	207(26.4)	60(13.7)	＜0.001
神经侵犯	91(11.6)	36(8.2)	0.078
切缘阳性	9(1.2)	4(0.9)	0.780
病理类型
鳞状分化	52(6.6)	18(4.1)	0.073
腺样分化	17(2.2)	12(2.7)	0.559
微乳头变异	20(2.6)	7(1.6)	0.317
神经内分泌分化	5(0.6)	2(0.5)	0.726
其他病理学变异	2(0.3)	0(0)	0.540
平均随访时间/月	30.5±29.3	35.4±25.2	＜0.001
注：^a)pN可分析1 032例，其中单纯RC队列618例，NAC+RC队列414例。

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表 2 NAC组病理缓解率例(%)

指标	NAC组(437例)	GC方案(361例)	其他方案^a)(76例)	P值
ypCR	99(22.6)	89(24.6)	10(13.1)	0.034
ypPR	142(32.5)	116(32.1)	26(34.2)	0.787
ypRR	241(55.1)	205(55.9)	36(47.3)	0.162
注：^a)包括GK方案61例，PC方案15例。

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表 3 PSM后关键临床参数比较例(%)，X±S

临床参数	RC组(361例)	NAC组(427例)	P值
男性	300(83.1)	333(78.0)	0.08
年龄/岁	63.7±8.8	62.9±7.7	0.15
临床T分期			0.71
cT₂	256(70.9)	314(73.5)
cT₃	85(23.5)	91(21.3)
cT_4a	20(5.5)	22(5.2)
临床N分期			0.83
cTanyN₀	314(87.0)	374(87.6)
cTanyN_1~3	47(13.0)	53(12.4)

下载: 导出CSV

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