| Background:Bladder urothelial carcinoma is one of the most common malignancies of the urinary system,and one of the most expensive cancer type in terms of life-time treatment costs.It is reported that nearly 75%of patients are initially diagnosed with non-muscle-invasive bladder cancer,and transurethral resection of bladder tumor is the gold standard for treatment,but the postoperative recurrence rate remains high.It is of vital importance to diagnose the recurrence of bladder cancer at an early stage to improve the prognosis.Studies have shown that urine pH is closely related to postoperative recurrence of ureteral cancer,but its role in predicting the recurrence of bladder cancer after transurethral resection of bladder tumor is not yet clear.Developing a risk model to predict the recurrence of non-muscle-invasive bladder cancer is of vital importance in terms of clinical practice and social-burden reliefing.Objective:To analyse the correlation between preoperative urine pH and the recurrence of nonmuscle-invasive bladder cancer patients who receiving transurethral resection of bladder tumor,and develop a risk model,as well as a web calculator,to predict the recurrence of non-muscleinvasive bladder cancer patients.Methods:The clinical information of 673 patients with newly diagnosed bladder cancer who were treated in the Department of Urology,Qilu Hospital of Shandong University,from January 1,2010 to December 31,2019 were enrolled retrospectively.All patients received transurethral resection of bladder tumors performed by experienced urologists,and were pathologically diagnosed with urothelial carcinoma,and all received standard bladder installation therapy.Clinical data were retrieved from the hospital information system and standard formats were used to collect the data.A total of 614 patients were enrolled in the current study.The primaryendpoint was the first recurrence-free survival.Univariate and multivariate COX regression analysis and Kaplan-Meier survival curves were used to examine the correlation between urine pH and postoperative recurrence.Univariate COX regression,LASSO regression and stepwise multivariate COX regression analysis were used to screen for the independent prognostic factors.R statistical software was used to develop the risk model and the web calculator to predict the postoperative recurrence-free survival in patients with non-muscle-invasive bladder cancer.The time-dependent receiver operating characteristic curve,calibration curve,clinical decision curve and Kaplan-Meier survival curves were used to evaluate the efficacy of the risk model.P<0.05 was considered statistically significant.Results:Univariate COX regression analysis demonstrated that urine pH(P=0.009)was an independent prognostic factor for predicting the recurrence of non-muscle-invasive bladder cancer patients after transurethral resection of bladder tumors.Kaplan-Meier survival curves demonstrated that the recurrence-free survival of the patients with urine pH>5.5 was significantly lower than that of patients with urine pH≤5.5(P=0.009).When it comes to subgroup analysis,in patients with smoking habits,patients with elevated preoperative urine White Blood Cells,and male patients,Kaplan-Meier survival curves indicated that the recurrence-free survival of the patients with urine pH>5.5 was significantly lower than that of the patients with urine pH≤5.5(P=0.008,P=0.012 and P=0.015).614 patients were randomly assigned into training set and validation set with the ratio of 3:1.Univariate COX regression,LASSO regression and stepwise multivariate COX regression analysis were applied in the training set,and the results showed that gender(P=0.041),urine White Blood Cells(P=0.020),tumor multiplicity(P<0.001),histological grade(P=0.050)and urine pH(P=0.009)were independent prognostic factors for predicting postoperative recurrence in patients with non-muscle-invasive bladder cancer.The risk model for predicting the postoperative recurrence-free survival of patients with non-muscle-invasive bladder cancer is developed incorporating the above five parameters,and the area under the curve of time-receiver operating characteristic curves of the 1-year,3-year and 5-year were 0.732,0.740 and 0.763,respectively.In the validation set,the areas under the curve were 0.661,0.714 and 0.71 8,respectively.The calibration curve of the training set was consistent with the ideal curve,and the calibration curve of the training set slightly less consistent,with the overall trend remaining consistent.The clinical decision curve of the training set suggested that it could bring clinical net benefit to the 1-year,3-year and 5-year recurrence-free survival of patients.And the clinical decision curve of the validation set was slightly worse,but remained consistent overall.A web calculator,based on the risk model,for predicting the recurrence-free survival of patients was developed and could be acquired from https://recurrent-risk.shinyapps.io/DynNomapp/.614 patients were assigned into low,medium and high risk groups based on the risk model using the software of X-tile,and Kaplan-Meier survival curves showed that the recurrence-free survival of the high risk group was significantly lower than that of the medium risk group and low risk group(P<0.001).Moreover,614 patients were scored by the European Organization for Research and Treatment of Cancer(EORTC),one of the most widely used bladder cancer recurrence risk prediction model,and Kaplan-Meier survival curves results showed that the recurrence-free survival of the patients with score 5-9 was significantly lower than that of the patients with score 1-4 and 0(P<0.001).The area under the curve of time-receiver operating characteristic curve of the risk model,and EORTC risk model of 1-year,3-year and 5-year recurrence-free survival were 0.652,0.689,0.699 and 0.684,0.672,0.692,respectively,which suggests that the prediction efficacy of our risk model is no worse that the EORTC risk model.Conclusions:Preoperative urine pH is an independent prognostic factor for recurrence of non-muscleinvasive bladder cancer.The risk model,based on the preoperative urine pH could effectively predict the recurrence risk of patients with non-muscle-invasive bladder cancer after TURBT,which may help clinicians to provide indivisulizes follow-up regimes non-muscle-invasive bladder cancer patients after surgery. |
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