Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Urol. 2021 Nov;206(5):1122-1131. doi: 10.1097/JU.0000000000001936. Epub 2021 Jun 28.
We sought to validate the association of plasma levels of urokinase-type plasminogen activator (uPA), its soluble receptor (SuPAR) and its inhibitor (PAI-one) with oncologic outcomes in a large cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).
We collected preoperative blood samples from 1,036 consecutive patients treated with RC for UCB. Plasma specimens were assessed for levels of uPA, SuPAR and PAI-one. Retrospective logistic and Cox regression analyses were performed to assess their correlation with clinical outcomes. The additional clinical net benefit provided by the biomarkers was evaluated using decision curve analysis.
Preoperative plasma uPA, SuPAR and PAI-one levels were significantly elevated in patients harboring adverse pathological features. Higher levels of all biomarkers were independently associated with an increased risk of lymph node metastasis; uPA levels were also independently associated with ≥pT3 disease. Preoperative uPA and SuPAR were independently associated with recurrence-free and cancer-specific survival. The addition of these biomarkers to standard pre-treatment and post-treatment models improved the discriminatory power for prediction of lymph node metastasis, ≥pT3 disease, and recurrence-free and cancer-specific survival by a prognostically significant margin.
We confirmed that elevated preoperative plasma levels of uPA, SuPAR and PAI-one are associated with features of aggressive disease and worse survival outcomes in patients treated with RC for UCB. These biomarkers hold potential in identifying patients who are likely to benefit from intensified/multimodal therapy. They also demonstrated the ability to improve the discriminatory power of predictive/prognostic models, thus refining personalized clinical decision-making.
我们旨在通过对接受根治性膀胱切除术（RC）治疗的大量膀胱癌患者队列进行研究，验证血浆尿激酶型纤溶酶原激活物（uPA）、其可溶性受体（SuPAR）及其抑制剂（PAI-1）水平与肿瘤学结局之间的相关性。
我们收集了 1036 例接受 RC 治疗的膀胱癌患者的术前血液样本。评估血浆标本中 uPA、SuPAR 和 PAI-1 的水平。采用回顾性逻辑和 Cox 回归分析评估它们与临床结局的相关性。通过决策曲线分析评估生物标志物提供的额外临床净效益。
术前血浆 uPA、SuPAR 和 PAI-1 水平在具有不良病理特征的患者中显著升高。所有生物标志物水平升高均与淋巴结转移风险增加独立相关；uPA 水平也与≥pT3 疾病独立相关。术前 uPA 和 SuPAR 与无复发生存和癌症特异性生存独立相关。这些生物标志物的加入可显著改善预测淋巴结转移、≥pT3 疾病、无复发生存和癌症特异性生存的预测模型的区分能力。
我们证实，术前血浆 uPA、SuPAR 和 PAI-1 水平升高与接受 RC 治疗的膀胱癌患者侵袭性疾病特征和生存结局较差相关。这些生物标志物具有识别可能受益于强化/多模式治疗的患者的潜力。它们还显示出改善预测/预后模型的区分能力的能力，从而优化了个性化临床决策。
