Prognostic Nutritional Index And Nomogram Predicting Recurrence-free Survival In Patients With Primary Non-muscle Invasive Bladder Cancer

Background and objectiveBladder cancer(BCa)is the sixth most commonly diagnosed cancer in the male population worldwide according to the latest published global cancer statistics.The majority of BCa occurs in men,and there is about a 10-fold variation in incidence rates internationally.Among the urogenital system cancers,bladder cancer is ranked second both in incidence and mortality.Approximately 75%of patients with BCa present with a disease confined to the non-muscle invasive bladder cancer(NMIBC).The prognostic nutritional index(PNI)which was described by Buzby et al is based on serum albumin levels and peripheral lymphocyte count,and was corroborated by Onodera et al.Several studies have confirmed the prognostic value of PNI in various cancers,such as hepatocellular carcinoma,renal cancer and so on.The most frequently used prognostic model for individual bladder cancer patient is European Organization for the Research and Treatment of Cancer-Genito-Urinary Cancer Group(EORTC-GUCG)risk scoring system,however,this system mainly depends on European population.Thus,a more accurate prognostic nomogram model for patients with NMIBC is needed to be achieved.To our knowledge,the value of PNI in NMIBC for predicting recurrence-free survival has not been investigated yet.Thus,the purpose of this study is to clarify the prognostic value of preoperative PNI among patients who had undergone transurethral resection of bladder tumors(TURBT)for NMIBC,and establish a nomogram to predict RFS for individual patients after surgery.MethodsThis retrospective analysis included clinicopathologic and follow-up data from 329 patients with NMIBC who had undergone transurethral resection of bladder tumors(TURBT)at the department of urology at the Qilu Hospital of Shandong University from January 2008 to December 2013.Visible or suspicious lesions were removed by TURBT.Due to limited number of BCa progression in this study,the endpoint in this study is RFS.RFS were defined as the time interval from the date of the initial TURBT to the date of recurrence which was confirmed by histopathology.Correlations between categorical variables were evaluated by the Pearson 's chi square test or Fisher's exact test in this study.The probable cutoff value level for the PNI was determined by applying receiver operating curve(ROC)analysis.In RFS analysis,the Kaplan-Meier method was used to evaluate the survival rates in different groups and the equivalences of the survival curves were tested by log-rank tests.Besides,the Cox proportional hazards regression model was applied in univariate and multivariate analyses.The nomogram provides a graphic representation linking an individual patient's multivariable prognostic factors to RFS probability of patient with NMIBC.Discrimination is measured by the concordance index(c-index)which is the area under the curve(AUC)of a ROC.The calibration of the model is assessed visually with calibration plots.A 45° line indicates perfect calibration—when the predictive value of the model perfectly matches the patient's actual risk.The two-sided p value of less than 0.05 is considered to be statistically significant.ResultsAccording to the EORTC risk scoring system,31 patients was regarded as low risk of recurrence,189 as intermediate risk of recurrence and 109 as high risk of recurrence.During the follow-up period,125 of the 329 patients experienced recurrence.5 in low risk group,61 in intermediate risk group and 59 in high risk group.Overall,RFS rate of patients with NMIBC was 82.7%at 1 year,66.1%at 3 years,and 43.2%at 5 years.The Kaplan-Meier survival analysis showed that preoperative PNI was significantly associated with RFS(p<0.001).Furthermore,we evaluated whether the PNI in different EORTC groups was associated with the RFS.No difference was found in patients of low risk group for RFS(p=0.815),but statistically difference was found in patients of intermediate risk group(p=0.013)and high risk group(p=0.044).To clarify the independent prognostic value of preoperative PNI for RFS,multivariate Cox proportional hazards regression analysis using age,tumor focal ity,tumor size,tumor grade,tumor stage and preoperative PNI as covariates revealed that age(HR=2.007,95%CI 1.036-3.885,p=0.039),tumor focality(HR=1.484,95%CI 1.039-2.119,p=0.030),tumor grade(G1,G2 or G3,HR=2.603,95%CI 1.186-5.713,HR=2.933,95%CI 1.228-7.003,p=0.015,respectively),tumor stage(pTa or pT1,HR=1.737,95%CI 1.108-2.724,p=0.016)and PNI(low or high,HR=0.598,95%CI 0.410-0.870,p=0.007)were independent predictors for RFS in patients with NMIBC.According to the multivariable Cox model,the nomogram can be used to predict the risk of BCa recurrence at 1-,3-and 5-years after primary surgery.The accuracy of this nomogram model was relatively high,with a c-index of 0.697.And calibration is another important indicator of nomogram.The calibration plots showed only a limited deviation from the ideal predictions.ConclusionThe present study shows the evaluation of preoperative PNI which can be regarded as an independent prognostic factor to predict RFS of patients with NMIBC.Moreover,the nomogram which included age,tumor stage,tumor grade,tumor focality and PNI could be useful to improve the personalized multidisciplinary therapy for patients with NMIBC.