非肌层浸润性膀胱癌行初次经尿道膀胱肿瘤电切术的术后复发危险因素分析

doi:10.19401/j.cnki.1007-3639.2023.05.008

摘要/Abstract

摘要：

背景与目的：非肌层浸润性膀胱癌（non-muscle invasive bladder cancer，NMIBC）患者行经尿道膀胱肿瘤电切术（transurethral resection of bladder cancer，TURBT）的术后复发率较高，分析NMIBC患者行初次TURBT术后复发危险因素的相关研究较少。本研究旨在分析NMIBC患者行初次TURBT的术后复发危险因素，有助于筛选复发高危人群，预防性采取相应的干预措施。方法：选取2015年12月—2020年5月在电子科技大学附属肿瘤医院行初次TURBT治疗的NMIBC患者197例，随访24~77个月，根据是否复发分为复发组（48例）和非复发组（149例）。对两组临床资料进行单因素分析，将单因素分析差异有统计学意义的指标纳入多因素logistic回归分析，筛选TURBT术后复发的可能危险因素。结果：单因素分析显示，未复发组初治时有肉眼血尿、二次电切、肿瘤T分期为T₁期、肿瘤分级为高级别、肿瘤多发及未行即刻膀胱内灌注化疗的占比低于复发组，差异有统计学意义（P<0.05）。两组的性别、年龄、肿瘤家族史、吸烟史、肿瘤大小及后续膀胱内灌注化疗对比差异无统计学意义（P>0.05）。两组中性粒细胞/淋巴细胞、中性粒细胞×血红蛋白/淋巴细胞的受试者工作特征（receiver operating characteristic，ROC）曲线显示差异无统计学意义（P>0.05）。多因素logistic回归分析显示，肿瘤T分期为T₁期、肿瘤分级为高级别、肿瘤多发及未行即刻膀胱内灌注化疗为NMIBC患者初次TURBT术后复发的独立危险因素（P<0.05，OR>1）。结论：NMIBC患者行初次TURBT术后复发与肿瘤分期、肿瘤分级、肿瘤数目、是否行即刻膀胱内灌注化疗密切相关，临床上可以采取对应的干预措施，降低患者术后的复发率。

关键词: 非肌层浸润性膀胱癌, 初次经尿道膀胱肿瘤电切术, 复发, 危险因素

Abstract:

Background and purpose: The recurrence rate of non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT) is high. There are few studies on the risk factors of recurrence in NMIBC patients after initial TURBT. Our study aimed to screen the high-risk population and take corresponding preventive intervention measures by analyzing the risk factors of recurrence in NMIBC patients after initial TURBT. Methods: A total of 197 NMIBC patients who received initial TURBT in The Cancer Hospital of the University of Electronic Science and Technology of China from December 2015 to May 2020 were selected and followed up for 24 to 77 months. Patients were divided into recurrence group (48 cases) and non-recurrence group (149 cases) according to the results. Univariate analysis was performed on the clinical data of the two groups, and the indicators with statistical significance were included in the multivariate logistic regression analysis to screen the possible risk factors of recurrence. Results: Univariate analysis showed that the difference was statistically significant between two groups in gross hematuria, secondary resection, T1 stage, high grade tumor, multiple tumor and lack of immediate intravesical therapy (P <0.05).There was no significant difference in gender, age, family history of tumor, smoking history, tumor size and subsequent intravesical therapy between two groups (P>0.05). The receiver operating characteristic (ROC) curves of the ratio of neutrophils to lymphocytes and the ratio of neutrophils and hemoglobin to lymphocytes showed no statistically significant difference between two groups (P>0.05). Multivariate logistic regression analysis showed that T1 stage, high grade tumor, multiple tumor and lack of immediate intravesical therapy were independent risk factors of recurrence in NMIBC patients after initial TURBT (P<0.05, OR > 1). Conclusion: The recurrence of NMIBC patients after initial TURBT is closely related to tumor stage, tumor grade, tumor number and immediate intravesical therapy. Corresponding intervention measures can be taken to reduce the postoperative recurrence rate in initial NMIBC patients.

Key words: Non-muscle invasive bladder cancer, Initial transurethral resection of bladder tumor, Recurrence, Risk factors

中图分类号:

R737.14

唐多才, 周术奎, 张桂银, 刘磊, 廖洪. 非肌层浸润性膀胱癌行初次经尿道膀胱肿瘤电切术的术后复发危险因素分析[J]. 中国癌症杂志, 2023, 33(5): 478-483.

TANG Duocai, ZHOU Shukui, ZHANG Guiyin, LIU Lei, LIAO Hong. Analysis of risk factors of recurrence in non-muscle invasive bladder cancer patients after initial transurethral resection of bladder tumor[J]. China Oncology, 2023, 33(5): 478-483.

图/表 2

表1

表2

参考文献 27

[1]	SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2016[J]. CA A Cancer J Clin, 2016, 66(1): 7-30. doi: 10.3322/caac.21332
[2]	ZHANG J, WANG Y Y, WENG H, et al. Management of non-muscle-invasive bladder cancer: quality of clinical practice guidelines and variations in recommendations[J]. BMC Cancer, 2019, 19(1): 1054. doi: 10.1186/s12885-019-6304-y pmid: 31694589
[3]	POWLES T, BELLMUNT J, COMPERAT E, et al. Bladder cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up[J]. Ann Oncol, 2022, 33(3): 244-258. doi: 10.1016/j.annonc.2021.11.012
[4]	BABJUK M, BURGER M, CAPOUN O, et al. European association of urology guidelines on non-muscle invasive bladder cancer (T_a, T₁, and carcinoma in situ)[J]. Eur Urol, 2022, 81(1): 75-94. doi: 10.1016/j.eururo.2021.08.010
[5]	WANG T W, YUAN H, DIAO W L, et al. Comparison of gemcitabine and anthracycline antibiotics in prevention of superficial bladder cancer recurrence[J]. BMC Urol, 2019, 19(1): 90. doi: 10.1186/s12894-019-0530-0
[6]	ZHENG R S, ZHANG S W, ZENG H M, et al. Cancer incidence and mortality in China, 2016[J]. J Natl Cancer Cent, 2022, 2(1): 1-9.
[7]	LU J L, XIA Q D, LU Y H, et al. Efficacy of intravesical therapies on the prevention of recurrence and progression of non-muscle invasive bladder cancer: a systematic review and network meta-analysis[J]. Cancer Med, 2020, 9(21): 7800-7809. doi: 10.1002/cam4.v9.21
[8]	SIKIC D, ECKSTEIN M, WEYERER V, et al. High expression of ERBB2 is an independent risk factor for reduced recurrence-free survival in patients with stage T₁ non-muscle invasive bladder cancer[J]. Urol Oncol, 2022, 40(2): 63.e9-63.63.e18.
[9]	SYLVESTER R J, VAN DER MEIJDEN A P, OOSTERLINCK W, et al. Predicting recurrence and progression in individual patients with stage T_a T₁ bladder cancer using EORTC risk tables: a combined analysis of 2 596 patients from seven EORTC trials[J]. Eur Urol, 2006, 49(3): 466-465; discussion 475-477. doi: 10.1016/j.eururo.2005.12.031
[10]	杨庆良, 陈志峰, 王军, 等. 非肌层浸润性膀胱癌患者经尿道膀胱肿瘤电切术后复发的影响因素[J]. 实用癌症杂志, 2022, 37(2): 309-311.
	YANG Q L, CHEN Z F, WANG J, et al. Factors affecting recurrence of non-myometrial invasive bladder cancer after transurethral resection of bladder tumor[J]. Pract J Cancer, 2022, 37(2): 309-311.
[11]	董建庭. 非肌层浸润性膀胱癌患者经尿道膀胱肿瘤电切术治疗后复发的现状及其危险因素分析[J]. 中国药物与临床, 2022, 22(3): 223-226.
	DONG J T. Recurrence of non-muscle invasive bladder cancer and risk factors in patients after transurethral resection of bladder tumor[J]. Chin Remedies & Clin, 2022, 22(3): 223-226.
[12]	薛炜, 邱建新, 桑楠, 等. 影响非肌层浸润性膀胱癌患者经尿道膀胱肿瘤电切术后复发的相关因素分析[J]. 实用医院临床杂志, 2019, 16(5): 30-33.
	XUE W, QIU J X, SANG N, et al. Analysis of related factors influencing recurrence of patients with non-muscle invasive bladder cancer after transurethral resection of bladder tumor[J]. Pract J Clin Med, 2019, 16(5): 30-33.
[13]	白恒舟, 乔保平. 200例非肌层浸润性膀胱癌复发及进展的危险因素分析[J]. 河南外科学杂志, 2017, 23(6): 39-41.
	BAI H Z, QIAO B P. Analysis of risk factors for recurrence and progression of non-muscular invasive bladder cancer in 200 cases[J]. Henan J Surg, 2017, 23(6): 39-41.
[14]	ZHANG Y Q, BREKKEN R A. Direct and indirect regulation of the tumor immune microenvironment by VEGF[J]. J Leukoc Biol, 2022, 111(6): 1269-1286. doi: 10.1002/JLB.5RU0222-082R
[15]	苟泓燊, 郑红岗, 段中琪. 经尿道膀胱肿瘤电切术术后即刻表柔比星灌注化疗在非肌层浸润性膀胱癌患者中的应用效果[J]. 癌症进展, 2021, 19(22): 2343-2346.
	GOU H S, ZHENG H G, DUAN Z Q. Effect of immediate epirubicin infusion chemotherapy after transurethral resection of bladder tumor in patients with non-muscular invasive bladder cancer[J]. Oncol Prog, 2021, 19(22): 2343-2346.
[16]	CUMBERBATCH M G K, FOERSTER B, CATTO J W F, et al. Repeat transurethral resection in non-muscle invasive bladder cancer: a systematic review[J]. Eur Urol, 2018, 73(6): 925-933. doi: 10.1016/j.eururo.2018.02.014
[17]	GONTERO P, SYLVESTER R, PISANO F, et al. The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T₁ high-grade/grade 3 bladder cancer treated with bacille Calmette-Guérin[J]. BJU Int, 2016, 118(1): 44-52. doi: 10.1111/bju.13354
[18]	FLAIG T W, SPIESS P E, AGARWAL N, et al. Bladder cancer, version 3. 2020, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2020, 18(3): 329-354. doi: 10.6004/jnccn.2020.0011
[19]	MANO R, BANIEL J, SHOSHANY O, et al. Neutrophil-to-lymphocyte ratio predicts progression and recurrence of non-muscle invasive bladder cancer[J]. Urol Oncol, 2015, 33(2): 67.e1-67.e7.
[20]	HEDRICK C C, MALANCHI I. Neutrophils in cancer: Heterogeneous and multifaceted[J]. Nat Rev Immunol, 2022, 22(3): 173-187. doi: 10.1038/s41577-021-00571-6
[21]	BULUT G, OZDEMIR Z N. Prognostic significance of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in metastatic colorectal cancer[J]. J Gastrointest Canc, 2022, 53(1): 1-6. doi: 10.1007/s12029-021-00616-y
[22]	ZHENG X Q, FAN H, LIU Y, et al. Hypoxia boosts aerobic glycolysis in carcinoma: a complex process for tumour development[J]. Curr Mol Pharmacol, 2022, 15(3): 487-501. doi: 10.2174/1874467214666210811145752
[23]	ZHAO R N, SHAN J H, NIE L H, et al. The predictive value of the ratio of the product of neutrophils and hemoglobin to lymphocytes in non-muscular invasive bladder cancer patients with postoperative recurrence[J]. J Clin Lab Anal, 2021, 35(8): e23883.
[24]	CHENG X F, ZHOU X C, YI M, et al. Preoperative aspartate transaminase/alanine transaminase ratio as a prognostic biomarker in primary non-muscle invasive bladder cancer: a propensity score-matched study[J]. BMC Urol, 2021, 21(1): 136. doi: 10.1186/s12894-021-00901-9
[25]	HUANG J G, ZHAO L W, WANG K, et al. Controlling nutritional status score evaluates prognosis in patients with non-muscle invasive bladder cancer[J]. Cancer Control, 2021, 28: 10732748211021078.
[26]	WANG Z Y, GAO W S, LI J, et al. Development and validation of a novel recurrence risk stratification for initial non-muscle invasive bladder cancer in the Han Chinese population[J]. J Cancer, 2020, 11(7): 1668-1678. doi: 10.7150/jca.38649 pmid: 32194779
[27]	GALESLOOT T E, GROTENHUIS A J, KOLEV D, et al. Genome-wide meta-analysis identifies novel genes associated with recurrence and progression in non-muscle invasive bladder cancer[J]. Eur Urol Oncol, 2022, 5(1): 70-83.
	DALLA E, PICCO R, NOVARA G, et al. Identification of a gene signature for the prediction of recurrence and progression in non-muscle invasive bladder cancer[J]. Mol Biomed, 2022, 3(1): 9. doi: 10.1186/s43556-022-00069-0

Data	Recurrence	No recurrence	χ²	P value
Gender			0.130	0.718
Male	37	111
Female	11	38
Age/year			1.421	0.233
≥65	26	66
<65	22	83
Family history of tumor			0.000	1.000
Yes	4	14
No	44	135
Smoking history			0.125	0.724
Yes	31	92
No	17	57
Gross hematuria			4.307	0.038
Yes	45	121
No	3	28
Secondary resection			4.109	0.043
Yes	26	56
No	22	93
Tumor stage			21.170	0.000
T₁	37	58
T_a	11	91
Tumor grade			23.530	0.000
G₁	10	91
G₃	38	58
Multiple tumor			12.994	0.000
No	14	88
Yes	34	61
Tumor size/cm			2.588	0.108
≥5	4	3
<5	44	146
Immediate intravesical therapy			15.469	0.000
Yes	38	145
No	10	4
Accomplish subsequent intravesical therapy			0.185	0.667
Yes	43	130
No	5	19

Data	β	Standard error	Wald	P value	OR (95% CI)
Secondary resection	0.163	0.409	0.159	0.690	1.177 (0.528-2.625)
Gross hematuria	0.633	0.679	0.868	0.352	1.883 (0.497-7.131)
Tumor stage	1.031	0.443	5.419	0.020	2.803 (1.177-6.674)
Tumor grade	1.145	0.477	5.750	0.016	3.142 (1.233-8.008)
Multiple tumor	0.810	0.399	4.128	0.042	2.247 (1.029-4.907)
Immediate intravesical therapy	1.758	0.680	6.686	0.010	5.800 (1.530-21.987)