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.
World J Urol. 2023 Jul;41(7):1861-1868. doi: 10.1007/s00345-023-04449-1. Epub 2023 Jun 9.
To evaluate the prognostic value and the clinical impact of preoperative serum cholinesterase (ChoE) levels on decision-making in patients treated with radical nephroureterectomy (RNU) for clinically non-metastatic upper tract urothelial cancer (UTUC).
A retrospective review of an established multi-institutional UTUC database was performed. We evaluated preoperative ChoE as a continuous and dichotomized variable using a visual assessment of the functional form of the association of ChoE with cancer-specific survival (CSS). We used univariable and multivariable Cox regression models to establish its association with recurrence-free survival (RFS), CSS, and overall survival (OS). Discrimination was evaluated using Harrell's concordance index. Decision curve analysis (DCA) was used to assess the impact on clinical decision-making of preoperative ChoE.
A total of 748 patients were available for analysis. Within a median follow-up of 34 months (IQR 15-64), 191 patients experienced disease recurrence, and 257 died, with 165 dying of UTUC. The optimal ChoE cutoff identified was 5.8 U/l. ChoE as continuous variable was significantly associated with RFS (p < 0.001), OS (p < 0.001), and CSS (p < 0.001) on univariable and multivariable analyses. The concordance index improved by 8%, 4.4%, and 7% for RFS, OS, and CSS, respectively. On DCA, including ChoE did not improve the net benefit of standard prognostic models.
Despite its independent association with RFS, OS, and CSS, preoperative serum ChoE has no impact on clinical decision-making. In future studies, ChoE should be investigated as part of the tumor microenvironment and assessed as part of predictive and prognostic models, specifically in the setting of immune checkpoint-inhibitor therapy.
评估术前血清胆碱酯酶（ChoE）水平对接受根治性肾输尿管切除术（RNU）治疗临床非转移性上尿路上皮癌（UTUC）患者决策的预后价值和临床影响。
对一个已建立的多机构 UTUC 数据库进行回顾性分析。我们使用 ChoE 与癌症特异性生存（CSS）之间关联的功能形式的直观评估，将术前 ChoE 作为连续变量和二分类变量进行评估。我们使用单变量和多变量 Cox 回归模型来建立它与无复发生存（RFS）、CSS 和总体生存（OS）的关系。使用 Harrell 的一致性指数评估判别能力。决策曲线分析（DCA）用于评估术前 ChoE 对临床决策的影响。
共有 748 名患者可用于分析。在中位数为 34 个月（IQR 15-64）的随访中，191 名患者出现疾病复发，257 名患者死亡，其中 165 名死于 UTUC。确定的最佳 ChoE 截断值为 5.8 U/l。在单变量和多变量分析中，ChoE 作为连续变量与 RFS（p<0.001）、OS（p<0.001）和 CSS（p<0.001）显著相关。RFS、OS 和 CSS 的一致性指数分别提高了 8%、4.4%和 7%。在 DCA 上，包括 ChoE 并没有提高标准预后模型的净收益。
尽管术前血清 ChoE 与 RFS、OS 和 CSS 独立相关，但它对临床决策没有影响。在未来的研究中，ChoE 应作为肿瘤微环境的一部分进行研究，并作为预测和预后模型的一部分进行评估，特别是在免疫检查点抑制剂治疗的背景下。
