Risk Factors And Prognostic Factors Of Newly Diagnosed Renal Cell Carcinoma With Pulmonary Metastasis:A SEER-based Analysis

Background and objectiveRenal cell carcinoma（RCC）is a malignant tumor originating in the epithelial system of the urinary tubules.It accounts for 80%-90%of primary renal neoplasms.The lung is the most common metastatic site of RCC,accounting for 40%～53%of distant metastasis.Some newly diagnosed renal cell carcinoma patients present with pulmonary nodules,however,the feature of these nodules is often difficult to be determined by conventional diagnostic methods.Therefore,to explore the risk factors of pulmonary metastasis of initially diagnosed RCC is helpful to comprehensively evaluate the risk of pulmonary metastasis in newly diagnosed RCC patients,and to provide a reference for the decision of disease staging and therapeutic regimen.Patients with advanced RCC have a poor prognosis,with a median survival time of only about 14 months and a 5-year survival rate of only about 8%.At present,system treatment led by targeted therapy occupies a dominant position,and the application value of the traditional treatment method of cytoreductive nephrectomy（CN）is widely debated.The purpose of this study was to conduct a big data analysis of patients with pulmonary metastasis of RCC at initial diagnosis through SEER（Surveillance,Epidemiology,and End Results）database,systematically study the risk factors for pulmonary metastasis of RCC at initial diagnosis and the prognostic factors of patients with pulmonary metastasis of initially diagnosed RCC,and identify the value of CN in the treatment of pulmonary metastasis of initially diagnosed RCC at the same time.Methods1.The newly diagnosed RCC patients included in the SEER database with explicit variables from 2010 to 2015 were enrolled.They were divided into the pulmonary metastasis group and the non-pulmonary metastasis group according to the presence or absence of pulmonary metastasis.Clinical characteristics of the two groups were described.Univariate and multivariate Logistic regression was used to analyze the risk factors for pulmonary metastasis in the newly diagnosed RCC patients.According to the Harvard University tumor risk index model,the OR values were classified as>7.0,3.0-7.0,1.5-3.0,1.1-1.5,and 0.9-1.1for extremely high risk,high-risk,medium-risk,low-risk,and non-risk factors,respectively.2.Kaplan-Meier method was used to plot the survival curves of patients in the pulmonary metastasis group and the non-pulmonary metastasis group,and the difference was examined by the Log-rank method.Univariate and multivariate Cox proportional risk model was used to analyze the common clinicopathological factors affecting the survival of patients in the pulmonary metastasis group to explore the prognostic factors.The primary endpoint was cancer-specific survival（CSS）,and the secondary endpoint was overall survival（OS）.3.According to CN was performed or not,the patients in the pulmonary metastasis group were divided into the CN group and the non-CN group.In order to ensure the balance of baseline characteristics in the two groups,propensity score matching（PSM）was performed,matching variables were the factors influencing the prognosis of patients with pulmonary metastasis in univariate Cox regression analysis（P<0.05）,and the setting range of the matching caliper value was 0.001-0.05.Chi-square test or Fisher’s exact probability was used to compare the difference between groups.Log-rank were used to test the survival difference between the two groups before and after matching.Cox regression was used to analyze the effect of CN on the prognosis of the two samples before and after matching.Results1.A total of 35,909 newly diagnosed RCC patients were included in this study,of which,1818（5.06%）had pulmonary metastasis.To be compared with the non-pulmonary metastasis group,the pulmonary metastasis group presented the following clinical characteristics:older at the diagnosis,predominantly male,slightly higher proportion of Caucasians,slightly higher proportion of bilateral simultaneous RCC,advanced T stage,high proportion of regional lymph node metastasis or other distant organs（bone,liver,brain）metastasis,and mainly pathological type was clear cell RCC（all P<0.001）.According to univariate Logistic analysis,the extremely high risk factors for pulmonary metastasis in newly diagnosis of RCC were as follows:T stage≥T₂,N₁,presence of bone,liver,or brain metastasis,and bilateral simultaneous RCC.Low-risk factors included age>54 years and male.Multivariate Logistic analysis found that the extremely high risk factors included:T stage≥T₂,presence of bone,liver or brain metastasis,and bilateral simultaneous RCC.The high-risk factor was N₁.The Low-risk factors included:age>54 years and male.The risk of pulmonary metastasis in papillary RCC（OR=0.30,P<0.001）and chromophobe RCC（OR=0.16,P<0.001）was likely lower than that in clear cell RCC.T₄ stage was the strongest risk factor for pulmonary metastasis（OR=21.75,P<0.001）.2.Survival analysis found that CSS was significantly shorter in patients with pulmonary metastasis（1818 cases）than in patients without pulmonary metastasis（34091 cases）（14months vs not reached,P<0.001）.Univariate Cox regression analysis showed that age≥67years,black race,unmarried,T₄,N₁,other distant organs（bone,liver,brain）metastasis,papillary RCC,and radiotherapy were prognostic risk factors.Multivariate Cox analysis showed that age≥67 years,T₄,N₁ and other distant organs（bone,liver,brain）metastasis were the factors associated with a worse prognosis.CN was protective factors.Pathological type of RCC was not an independent factor for the prognosis of newly diagnosed RCC with pulmonary metastasis.3.Through PSM,there were 342 cases matched successfully in the CN group and the non-CN group,and the caliper value was 0.004.There was no statistically significant difference in baseline data between the two groups after matching（P>0.05）.After PSM,both mCSS（22 vs 9 months,P<0.001）and mOS（20 vs 8 months,P<0.001）in the CN group showed significant survival benefit compared with the non-CN group;Univariate analysis showed that CN significantly improved prognosis（CSS:HR=0.50,P<0.001;OS:HR=0.48,P<0.001）;Multivariate Cox analysis showed that CN still had a strong protective effect on improving prognosis（CSS:HR=0.50,P<0.001;OS:HR=0.49,P<0.001）.Conclusions1.Patients with T stage≥T₂,regional lymph node or other organs（bone,liver,brain）metastasis have a higher risk of pulmonary metastasis.Among them,T stage has the strongest correlation with the occurrence of pulmonary metastasis in newly diagnosed RCC patients.2.The patients with pulmonary metastasis of newly diagnosed RCC have short survival and poor prognosis.Age≥67 years,T₄,regional lymph node or other distant organs（bone,liver,brain）metastasis are the risk factors for the prognosis,and CN is the protective factor.Pathological type of RCC is not an independent factor for the prognosis of newly diagnosed RCC with pulmonary metastasis.