Survival Analysis Of Adjuvant Sunitinib In High-risk Locoregional Clear Cell Renal Cell Carcinoma After Radical Nephrectomy

Background: The incidence of renal cell carcinoma(RCC)has increased steadily in recent years.A majority of patients had localized renal carcinoma(without distant metastasis)at the initial diagnosis.Although most of such patients can be cured by surgery,the postoperative recurrence rate is much higher in patients from the high-risk recurrence group than those from the medium and low-risk recurrence groups,and no standard regimen for postoperative adjuvant therapy has been suggested by the guidelines.Safe,effective and feasible regimens for adjuvant therapy after radical nephrectomy for high-risk localized RCC are very important.Objective: To investigate the preventive effect of Sutent,Sunitinib Malate Capsules,as adjuvant therapy for tumor recurrence after radical nephrectomy for high-risk localized clear-cell renal cell carcinoma(ccRCC).Methods: The clinical data of 92 high-risk(Leibovich score ≥6)patients with localized ccRCC were retrospectively analyzed in Air Force General Hospital and in 307 hospital between January 2010 and December 2015.All patients who underwent radical nephrectomy voluntarily made their choices for whether or not to receive postoperative adjuvant therapy with Sunitinib.According to whether the target-assisted postoperative therapy was conducted or not,statistical data were collected and divided into two groups,i.e.the treatment group(40 cases),receiving postoperative adjuvant therapy with Sunitinib and the observation group(52 cases),undergoing routine imaging monitoring postoperatively.Univariate analysis was performed using the Kaplan-Meier method to filter out the insignificant variables.Based on the result of univariate analysis and the research significance of variables,the pathological stage of tumor,local lymph node metastasis,tumor necrosis,tumor diameter,Fuhrman nuclear grade and medication of Sunitinib were included and a Cox regression model was established to conduct a multivariate analysis on the difference in disease free survival between the treatment group and the observation group and to observe its influencing factors.Results: General condition of patients: 32 cases(34.78%),including 12 cases in the treatment group and 20 cases in the control group,out of the 92 patients indicated progression of disease(recurrence or death),but no statistical significance existed in comparison of disease progression between the two groups(P=0.389).It is believed that there was no significant difference in the progression of disease between the two groups;univariate analysis showed that,in terms of disease-free survival,the median survival time was 63 months,mean 58.38±3.1 months,for the treatment group and the median survival time was 57 months,mean 56.1±3.2 months,for the control group,no statistical difference in DFS existed between the two groups(P=0.531).In addition,DFS was irrelevant to the patients’ gender(P=0.340)and age(P=0.238),and was related to pathological stage of tumor(P=0.000),local lymph node metastasis(P=0.032),tumor necrosis(P=0.023),tumor diameter(P=0.005)and Fuhrman nuclear grade(P=0.011),and the result of multivariate analysis using Cox regression model showed that the tumor diameter(P=0.006),Fuhrman grade(P=0.001),pathological stage(P=0.004),tumor necrosis(P=0.032)and local lymph node metastasis(P=0.001)are all independent risk factors affecting the progression of postoperative recurrence of high-risk localized ccRCC,but there was no significant correlation between Sunitinib medication and postoperative DFS(P=0.124).Conclusion:(1)Multivariate analysis using the established Cox regression model after the exclusion of confounding variables indicated that,as the main outcome measures of this study,there was no significant prolongation in DFS of these patients in comparison between the postoperative adjuvant therapy with Sunitinib for high-risk(Leibovich score ≥6)patients with localized ccRCC and the management of routine imaging monitoring,i.e.there was no confirmed clinical benefit in the medication of Sunitinib.The results of this study do not support Sunitinib as the ideal medication for postoperative adjuvant therapy of patients with high-risk localized clear-cell renal cell carcinoma.(2)In this study,the secondary outcome measures of ‘tumor diameter’,‘Fuhrman nuclear grade’,‘pathological stage of tumor’,‘tumor necrosis’ and ‘local lymph node metastasis’ are independent risk factors affecting the progression of tumor recurrence in high-risk localized ccRCC.There was no significant correlation between the patients’ ‘age’ and ‘gender’,and the progression of postoperative tumor recurrence.