Fangzheng Zhao,1 Nienie Qi,1 Xihao Shen,2 Zhuang Xiong,1 Ning Xue,1 Yang Xu,1 Junqi Wang,1 Haitao Zhu1 1Department of Urology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Peopleâs Republic of China; 2The First Clinical Medical College of Nanjing Medical University, NanJing, Peopleâs Republic of ChinaCorrespondence: Junqi Wang; Haitao Zhu, Department of Urology, the Affiliated Hospital of Xuzhou Medical University, No. 99 Huaihai West Road, Quanshan District, Xuzhou, 221100, Peopleâs Republic of China, Tel +86-18761389113, Fax +86051685609999, Email 595851028@qq.com; xyfy1096@163.comPurpose: This study was conducted to evaluate the correlation between the free ferrous protoporphyrin and reactive oxygen species (FH and ROS) combined test and the tumor grade and stage in a pathologically confirmed uroepithelial carcinoma (UC) patient population.Patients and Methods: In this retrospective study, we enrolled patients newly diagnosed with UC between May 2020 and June 2021. All patients were classified as FH(+) and ROS(+), FH(+) and ROS(-), or FH(-) and ROS(-), based on the FH and ROS combined test of voided urine. Demographic information, pathological results, and status of the FH and ROS combined test were reviewed retrospectively. The relationship between FH and ROS combined test status and tumor stage and grade was evaluated using logistic regression.Results: This study included 120 UC patients with a median age of 69 years (interquartile range [IQR] 62â 77 years). Eighteen patients (15%) were diagnosed with upper tract urothelial carcinoma, and the others (85%) were diagnosed with bladder cancer. The pathological stages for those with FH(+) and ROS(+) at diagnosis were 25.0% Ta, 45.8% T1, and 29.2% â¥T2. The pathological stages for those with FH(+) and ROS(-) at diagnosis were 23.5% Ta, 35.3% T1, and 41.2% â¥T2. The pathological stages for those with FH(-) and ROS(-) at diagnosis were 52.6% Ta, 26.3% T1, and 21.1% â¥T2. After adjusting for clinical factors, including age, sex, and smoking history, FH(+) and ROS(-) were independent risk factors for muscle-invasive UC (â¥T2 stage) at diagnosis (odds ratio [OR] 3.379; 95% confidence interval [CI] 1.103â 10.355; P=0.033) in the univariate and multivariate logistic regression analyses.Conclusion: Among patients with newly diagnosed UC, FH(+) and ROS(-) might have an association with a more advanced pathological stage. This finding may help differentiate between patients with aggressive diseases and those who may benefit from organ-sparing surgery.Keywords: urothelial carcinoma, free ferrous protoporphyrin, reactive oxygen species, stage, grade