Table 1_Preoperative fibrinogen-to-lymphocyte ratio as a prognostic biomarker for non-muscle-invasive bladder cancer.docx

ObjectiveAlthough the fibrinogen-to-lymphocyte ratio (FLR) is an established prognostic biomarker in various solid tumors, its role in non-muscle-invasive bladder cancer (NMIBC) remains poorly defined. This study aimed not only to investigate the predictive value of preoperative FLR for overall survival (OS) in NMIBC patients undergoing transurethral resection of bladder tumor (TURBt), but also to develop and validate a novel FLR-based nomogram as a practical clinical tool.
MethodsThis retrospective study enrolled 304 NMIBC patients who underwent TURBt at the Shijiazhuang People’s Hospital between November 2013 and January 2024, with OS as the primary endpoint. The optimal prognostic cutoff for FLR was determined by maximizing the Youden index via receiver operating characteristic (ROC) curve analysis. Propensity score matching (1:2) was employed to balance baseline confounders. The dose-response relationship between continuous FLR and mortality risk was evaluated using restricted cubic splines (RCS), which confirmed a linear association. Subsequently, independent prognostic factors identified through Cox proportional hazards regression were integrated to construct a nomogram. The model’s predictive accuracy and clinical utility were then comprehensively evaluated using the concordance index (C-index), calibration curves, time-dependent ROC curves, and decision curve analysis (DCA).
ResultsThe optimal FLR cutoff was identified as 2.91. Patients in the high-FLR group (FLR ≥ 2.91) exhibited significantly poorer OS (P < 0.001) and cancer-specific survival (CSS; P = 0.004). RCS analysis confirmed a significant positive linear association between increasing FLR levels and all-cause mortality risk. Critically, multivariate Cox regression validated FLR as an independent predictor for both OS (Hazard Ratio (HR): 1.520, 95% Confidence Interval (CI): 1.149-2.010) and CSS (HR: 1.536, 95% CI: 1.033-2.284). Integrating FLR into a baseline model improved the C-index for OS prediction from 0.739 to 0.772. The resulting nomogram demonstrated robust discrimination (C-index: 0.772), excellent calibration, and superior net clinical benefit in DCA.
ConclusionPreoperative FLR is an independent predictor of overall survival in NMIBC, characterized by a robust linear dose-response relationship with mortality risk. This cost-effective biomarker, integrated into our validated nomogram, enhances risk stratification to guide personalized postoperative management.

研究目的：尽管纤维蛋白原与淋巴细胞比值（fibrinogen-to-lymphocyte ratio, FLR）作为一种已确立的预后生物标志物，在多种实体瘤中已有广泛应用，但其在非肌层浸润性膀胱癌（non-muscle-invasive bladder cancer, NMIBC）中的作用仍有待明确。本研究不仅旨在探讨经尿道膀胱肿瘤切除术（transurethral resection of bladder tumor, TURBt）治疗的NMIBC患者术前FLR对总生存期（overall survival, OS）的预测价值，同时还开发并验证了一种基于FLR的新型列线图，以作为实用的临床工具。
研究方法：本回顾性研究纳入2013年11月至2024年1月于石家庄市人民医院接受TURBt治疗的304例NMIBC患者，以OS为主要研究终点。通过受试者工作特征（receiver operating characteristic, ROC）曲线分析，以最大化约登指数的方式确定FLR的最佳预后截断值。采用1:2倾向性得分匹配以平衡基线混杂因素。使用限制性立方样条（restricted cubic splines, RCS）分析连续型FLR与死亡风险之间的剂量-反应关系，结果证实二者呈线性关联。随后，通过Cox比例风险回归模型筛选出的独立预后因素被整合，以构建列线图。最终通过一致性指数（concordance index, C-index）、校准曲线、时间依赖性ROC曲线及决策曲线分析（decision curve analysis, DCA），全面评估该模型的预测准确性与临床实用性。
研究结果：本研究确定FLR的最佳截断值为2.91。FLR≥2.91的高FLR组患者的OS（P<0.001）与癌症特异性生存期（cancer-specific survival, CSS；P=0.004）均显著更差。RCS分析证实，FLR水平升高与全因死亡风险之间存在显著的正向线性关联。尤为关键的是，多因素Cox回归分析证实FLR是OS（风险比（Hazard Ratio, HR）：1.520，95%置信区间（Confidence Interval, CI）：1.149~2.010）与CSS（HR：1.536，95%CI：1.033~2.284）的独立预测因素。将FLR纳入基线模型后，OS预测的C-index从0.739提升至0.772。所构建的列线图表现出良好的区分度（C-index：0.772）、极佳的校准度，且在DCA中显示出更优的净临床获益。
研究结论：术前FLR是NMIBC患者总生存期的独立预测因素，且与死亡风险存在显著的线性剂量-反应关系。这种具备成本效益的生物标志物经整合至本研究验证的列线图后，可优化风险分层，进而指导个体化术后管理。