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术前血浆血管内皮生长因子水平在根治性膀胱切除术治疗膀胱尿路上皮癌中的价值

The Value of Preoperative Plasma VEGF Levels in Urothelial Carcinoma of the Bladder Treated with Radical Cystectomy.

作者信息

Mori Keiichiro, Schuettfort Victor M, Katayama Satoshi, Laukhtina Ekaterina, Pradere Benjamin, Quhal Fahad, Sari Motlagh Reza, Mostafaei Hadi, Grossmann Nico C, Rajwa Pawel, König Frederik, Aydh Abdulmajeed, Soria Francesco, Moschini Marco, Karakiewicz Pierre I, Lotan Yair, Scherr Douglas, Haydter Martin, Nyirady Peter, Teoh Jeremy Y C, Egawa Shin, Compérat Eva, Shariat Shahrokh F

机构信息

Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.

Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

Eur Urol Focus. 2022 Jul;8(4):972-979. doi: 10.1016/j.euf.2021.08.006. Epub 2021 Aug 26.

Abstract

BACKGROUND

Elevated preoperative plasma levels of the angiogenesis-related marker VEGF have been associated with worse oncological outcomes in various malignancies.

OBJECTIVE

To investigate the predictive/prognostic role of VEGF in patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC).

DESIGN, SETTING, AND PARTICIPANTS: VEGF plasma levels were measured preoperatively in 1036 patients with UCB who underwent RC.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

The correlation between plasma VEGF levels and pathological and survival outcomes was assessed using logistic regression and Cox regression analyses. Discrimination was assessed using the concordance index (C index). The clinical net benefit was evaluated using decision curve analysis (DCA).

RESULTS AND LIMITATIONS

Patients with higher pretreatment plasma VEGF levels had poorer recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) according to log-rank tests (all p < 0.001). Higher VEGF levels were not independently associated with higher risk of lymph node metastasis, ≥pT3 disease, or non-organ-confined disease (all p > 0.05). Preoperative plasma VEGF levels were independently associated with RFS, CSS, and OS in preoperative and postoperative multivariable models. However, in all cases the C index increased by <0.02 and there was no improvement in net benefit on DCA. A limitation is that none of the patients received current elements of standard of care such as neoadjuvant chemotherapy.

CONCLUSIONS

Elevated plasma VEGF levels were associated with features of biologically and clinically aggressive disease such as worse survival outcomes among patients with UCB treated with RC. However, VEGF appears to have relatively limited incremental additive value in clinical use. Further study of VEGF for UCB prognostication is warranted before routine use in clinical algorithms.

PATIENT SUMMARY

Currently available models for predicting outcomes in bladder cancer are less than optimal. A protein called vascular endothelial growth factor (VEGF), which is a marker of the formation of blood vessels (angiogenesis), may have a role in predicting survival outcomes in bladder cancer.

摘要

背景

术前血浆中血管生成相关标志物血管内皮生长因子(VEGF)水平升高与多种恶性肿瘤较差的肿瘤学结局相关。

目的

探讨VEGF在接受根治性膀胱切除术(RC)治疗的膀胱尿路上皮癌(UCB)患者中的预测/预后作用。

设计、研究地点和参与者:对1036例行RC的UCB患者术前测定血浆VEGF水平。

结局测量和统计分析

采用逻辑回归和Cox回归分析评估血浆VEGF水平与病理及生存结局之间的相关性。使用一致性指数(C指数)评估辨别力。使用决策曲线分析(DCA)评估临床净获益。

结果和局限性

根据对数秩检验,术前血浆VEGF水平较高的患者无复发生存期(RFS)、癌症特异性生存期(CSS)和总生存期(OS)较差(所有p<0.001)。较高的VEGF水平与淋巴结转移、≥pT3期疾病或非器官局限性疾病的较高风险无独立相关性(所有p>0.05)。术前和术后多变量模型中,术前血浆VEGF水平与RFS、CSS和OS独立相关。然而,在所有情况下,C指数增加<0.02,DCA的净获益无改善。局限性在于没有患者接受新辅助化疗等当前标准治疗要素。

结论

血浆VEGF水平升高与生物学和临床侵袭性疾病的特征相关,如接受RC治疗的UCB患者生存结局较差。然而,VEGF在临床应用中的增量附加值似乎相对有限。在临床算法中常规使用之前,有必要对VEGF用于UCB预后进行进一步研究。

患者总结

目前可用的预测膀胱癌结局的模型并不理想。一种名为血管内皮生长因子(VEGF)的蛋白质是血管形成(血管生成)的标志物,可能在预测膀胱癌生存结局中发挥作用。

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