Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Cancer Immunol Immunother. 2022 Jan;71(1):85-95. doi: 10.1007/s00262-021-02953-0. Epub 2021 May 23.
Preoperative plasma levels of Interleukin 6 (IL6) and its soluble receptor (IL6sR) have previously been associated with oncologic outcomes in urothelial carcinoma of the bladder (UCB); however, external validation in patients treated with radical cystectomy (RC) for UCB is missing.
PATIENTS/METHODS: We prospectively collected preoperative plasma from 1,036 consecutive patients at two institutes. These plasma specimens were assessed for levels of IL6 and IL6sR. Logistic and Cox regression analyses were used to assess the correlation of plasma levels with pathologic and survival outcomes. The additional clinical net benefits of preoperative IL6 and IL6sR were evaluated using decision curve analysis (DCA).
Median IL6 and IL6sR plasma levels were significantly higher in patients with adverse pathologic features. Elevated biomarker levels were independently associated with an increased risk for lymph node metastasis and ≥ pT3 disease. Both biomarkers were independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The addition to, respectively, fitted pre- and postoperative prognostic models improved the predictive accuracy for lymph node metastasis, ≥ pT3 disease, RFS and CSS on DCA.
We confirmed that elevated preoperative plasma levels of IL6 and IL6sR levels are associated with worse oncological disease survival in patients treated with RC for UCB in a large multicenter study. Both biomarkers hold potential in identifying patients with adverse pathological features that may benefit from intensified/multimodal therapy and warrant inclusion into predictive/prognostic models. They demonstrated the ability to improve the discriminatory power of such models and thus guide clinical decision making.
白细胞介素 6（IL6）及其可溶性受体（IL6sR）的术前血浆水平先前与膀胱癌（UCB）的肿瘤学结果相关；然而，在接受根治性膀胱切除术（RC）治疗 UCB 的患者中缺乏外部验证。
患者/方法：我们在两个机构前瞻性地收集了 1036 例连续患者的术前血浆。这些血浆标本用于评估 IL6 和 IL6sR 的水平。逻辑和 Cox 回归分析用于评估血浆水平与病理和生存结果的相关性。使用决策曲线分析（DCA）评估术前 IL6 和 IL6sR 的额外临床净获益。
具有不良病理特征的患者的 IL6 和 IL6sR 血浆水平中位数显着升高。升高的生物标志物水平与淋巴结转移和≥pT3 疾病的风险增加独立相关。两种生物标志物均与无复发生存（RFS）、癌症特异性生存（CSS）和总生存（OS）独立相关。在分别添加到术前和术后预后模型中，改善了 DCA 中对淋巴结转移、≥pT3 疾病、RFS 和 CSS 的预测准确性。
我们在一项大型多中心研究中证实，在接受 RC 治疗 UCB 的患者中，术前血浆中升高的 IL6 和 IL6sR 水平与较差的肿瘤生存相关。这两种生物标志物都有可能识别出具有不良病理特征的患者，这些患者可能受益于强化/多模式治疗，并需要纳入预测/预后模型。它们证明了提高此类模型区分能力的能力，从而指导临床决策。
