The Value Of Systemic Inflammatory Markers In The Prognosis Of Patients With Non-Muscle Invasive Bladder Cancer

【Background】Bladder cancer(BC)stands as the tenth most prevalent malignancy worldwide,posing a significant burden on public health.The disease is broadly categorized into two subtypes based on the extent of tumor invasion of muscular tissue: non-muscular invasive bladder cancer(NMIBC)and muscular invasive bladder cancer(MIBC).The former accounts for approximately 75% of the total BC cases,and the latter is a more aggressive variant associated with a poorer prognosis.In the clinical setting,transurethral resection of bladder tumor(TURBT)is the preferred method for managing NMIBC,followed by conventional bladder irrigation.However,there is an unmet need for biomarkers that can serve as reliable predictors of NMIBC outcomes.Identifying such biomarkers is crucial to guide clinical decision-making and counseling of patients.Therefore,extensive research efforts have been focused on discovering effective and trustworthy biomarkers for NMIBC management.Extensive research has revealed a pivotal association between the tumor microenvironment(TME)and the systemic inflammatory response,unveiling a complex interplay that regulates tumor growth and progression.Among the myriad of predictors,systemic inflammatory markers outshine the rest with their inherent advantages of being cost-effective and effortlessly accessible.【Objective】Exploring the value of systemic inflammatory markers in the prognosis of non-muscular invasive bladder cancer patients.【Methods】Patients diagnosed with NMIBC and treated with TURBT surgery in the Department of Urology,The Second Hospital of Guangzhou Medical University between January 1,2017 and December 31,2021 were selected,and 77 patients were finally included according to the inclusion and exclusion criteria,with the final follow-up in January 2023.First,a thorough review of the medical record system was performed to gather essential clinical data,including gender,age,height,weight,body mass index,smoking history,hypertension status,tumor size,number,T-stage,and pathological grading.Next,the receiver operating characteristic(ROC)curves were plotted for the neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),lymphocyte-monocyte ratio(LMR),and systemic immune-inflammation index(SII).The area under the curve(AUC)was calculated to evaluate the predictive power of each marker.The optimal cut-off value was selected based on the maximum Youden’s index,and the patients were stratified into low and high-risk groups.Further,the Kaplan-Meier survival method was utilized to generate the relapse-free survival(RFS)curves for each clinical factor,and the log-rank test was employed to assess the differences between the groups.The RFS was compared between the high and low levels of NLR,PLR,LMR,and SII,respectively.Lastly,the Cox univariate and multivariate analyses were carried out to determine whether NLR,PLR,LMR,and SII were independent risk factors for RFS,with statistical significance set at P<0.05.【Results】1.A nuanced analysis of 77 patients diagnosed with non-muscular invasive b-ladder cancer(NMIBC)was conducted,featuring a median age of 68 years with a mean age of 66.36(53.16～79.56)years,alongside a median follow-up time of 24 months,where tumor recurrence was detected in 22 patients during the follow-up period.Based on the receiver operating characteristic(ROC)curve results,the cutting-edge values for SII,NLR,PLR,and LMR were meticulously scrutinized,inferring that the cut-off values for SII,NLR,PLR,and LMR were 499.08,2.38,117.2,and 3.12,respectively,while the area under the ROC curve for each index was0.730,0.734,0.618,and 0.674,respectively.2.Analysis of patients’ clinical data and pathological characteristics with each systemic inflammatory index revealed that: history of hypertension(P= 0.004),tumor size(P= 0.014),tumor number(P= 0.001),T-stage(P= 0.001)and risk grouping(P=0.036)were statistically different in the distribution between SII subgroups;history of hypertension(P= 0.003),tumor number(P= 0.002),T-stage(P<0.001)and pathological grade(P= 0.035)were statistically different in the distribution between NLR subgroups;number of tumors(P= 0.021)and T-stage(P= 0.039)were statistically different in the distribution between PLR subgroups;history of hypertension(P= 0.008),number of tumors(P= 0.001)and T staging(P= 0.006)were statistically different in the distribution between LMR subgroups.3.The patients were divided into recurrence group(n=22)and non-recurrence group(n=55)according to their postoperative prognosis,and the SII,NLR,PLR and LMR of NMIBC patients in the two groups were subjected to Mann Whitney U test respectively,and found that the differences in SII(P=0.001),NLR(P=0.008)and LMR(P=0.049)of patients with different prognosis were statistically significant;the patients with different prognosis The PLR of patients with different prognosis was not found to be statistically different(P=0.18).4.The prognosis of NMIBC patients was compared with their clinical data and.Log-Rank test of pathological characteristics revealed that SII(P<0.001),NLR(P=0.003),tumor size(P=0.001),tumor number(P=0.004),T-stage(P<0.001),histological grade(P=0.001),and risk grouping(P=0.006)correlated with postoperative RFS of patients,while PLR,LMR,gender,age,BMI,history of smoking,and history of hypertension did not correlate statistically with postoperative RFS in patients.5.According to the univariate analysis,tumor size(HR=4.328,P=0.001),tumor number(HR=2.644,P=0.027),T-stage(HR=6.429,P<0.001),histological grade(HR=5.087,P=0.001),risk group(HR=3.649,P=0.001),SII(HR=5.275,P<0.001),and NLR(HR=3.734,P=0.003)were strongly associated with patients’ postoperative RFS,and further multifactorial analysis showed that SII(HR=3.132,P=0.026)and tumor size(HR=2.901,P=0.036)were independent influences in predicting NMIBC recurrence.【Conclusions】1.The magnetic areas beneath the receiver operating characteristic(ROC)curves of both SII and NLR groups astutely reached 0.730 and 0.734,respectively,within the clinically significant range of 0.7～0.9.These impressive findings provide compelling evidence that SII and NLR could stand as valid biological indicators for predicting tumor recurrence in patients with non-muscular invasive bladder cancer(NMIBC).2.Taking into account various indicators,our results highlight a robust correlation between SII,NLR,tumor size,tumor number,T-stage,tumor histological grading,and risk grouping with the straight tumor recurrence in non-muscular invasive bladder cancer(NMIBC)patients.Excitingly,SII ≥ 499.08 and the maximum tumor diameter > 3 cm were precisely identified as autonomous risk factors for forecasting high-risk groups vulnerable to postoperative recurrence in NMIBC patients.These findings hold substantial clinical implications,enabling medical practitioners to adjust the patient’s treatment plan and follow-up period,depending on the specific needs and scenarios of individual patients.