| Part I: Analysis of risk factors for bone metastasis in renal cell carcinoma and establishment of predictive nomogram based on international public database Objective:The purpose of this study was to determine the risk factors for bone metastasis in renal cell carcinoma(RCC)based on a large population analysis,establish and validate a predictive nomogram.So as to provide a basis for the identification and screening strategies for high-risk groups of bone metastasis in RCC.Methods:Data were obtained for RCC patients from Surveillance,Epidemiology,and End Results(SEER)database between 2010 and 2015,established a cohort of eligible patients.All patients were divided into Modeling group(between 2010 and 2013)and Validation group(between 2014 and 2015).Univariate and multivariate factors logistic regression were conducted to identify the risk factors associated with bone metastases in RCC patients.A predictive nomogram was constructed.Bootstrap method was used for internal validation,and validation group were used for external validation.The area receiver operating characteristic curve(AUC)was calculated and the calibration curve was drawn for the accuracy and consistency of the predictive nomogram.Results:A total of 36,056 RCC patients were enrolled in the modeling group,including 23,190 males and 12,866 females,with an average age of 61.5 years.There were 1182(3.28%)patients with RCC with synchronous bone metastasis.The results of multiple logistic regression showed that elder patients(40-70y: OR=1.97,95%CI: 1.22-3.19;Age?70y: OR=2.10,95%CI: 1.29-3.44,P=0.012),Male(OR=1.23,95%CI: 1.07-1.41,P=0.004),higher T stage(T2: OR=2.02,95%CI: 1.67-2.44;T3: OR=1.52,95%CI: 1.28-1.80;T4: OR=2.34,95%CI: 1.77-3.10,P<0.001),poor tumor grade(Grade II: OR=1.16,95%CI: 0.87-1.54;Grade III: OR=1.91,95%CI: 1.44-2.55;Grade IV: OR=1.76,95%CI: 1.26-2.46,P<0.001),lymph node metastasis(OR=2.37,95%CI : 1.97-2.85,P<0.001),brain metastasis(OR=2.60,95%CI: 1.99-3.41,P<0.001),liver metastasis(OR=2.79,95%CI: 2.20-3.55,P<0.001),lung metastasis(OR=6.52,95%CI: 5.52-7.69,P<0.001)were positively correlated with the occurrence of bone metastasis of RCC.Papillary carcinoma(OR=0.54,95%CI: 0.43-0.67,P<0.001)and chromophobe cell carcinoma(OR=0.33,95%CI: 0.21-0.51,P<0.001)were negatively correlated with the occurrence of bone metastasis of RCC.The predictive nomogram was constructed based on the above factors.The AUC of internal and external validation were 0.863(95%CI: 0.846-0.880),0.858(95%CI: 0.843-0.873)repectively.The calibration curve showed a good consistency in the predictive nomogram.Conclusions:The incidence of synchronous bone metastasis of RCC was 3.28%.Advanced age,male,higher T stage,lymph node involvement,poor tumor grade,lung metastasis,liver metastasis,brain metastasis and clear cell carcinoma were the risk factors for bone metastasis in RCC patients.The nomogram for predicting the risk of bone metastasis of RCC has a high prediction,which can assist in guiding the screening of in RCC with bone metastasis in clinical practice.More studies are needed to carry out to validation of the prediction model in the future.Part II: Analysis of prognostic factors for bone metastasis in RCC,establishment and validation of the prognostic nomograms based on international public database Objective:To determine prognostic factors for RCC patients with bone metastasis,establish and validate the prognostic nomograms for RCC patients with bone metastasis.Methods:Data were obtained for RCC patients with bone metastasis from the SEER database between 2010 and 2015.All patients were divided into Modeling group(between 2010 and 2013)and Validation group(between 2014 and 2015).Kaplan-Meier curves and log-rank tests were used to estimate the overall survival(OS)for different subgroups and identify the prognostic factors for RCC patients with bone metastasis.Multivariate COX regression analysis was performed to identify independent prognostic factors for RCC patients with bone metastasis.The prognostic nomograms were constructed.Bootstrap method was used for internal validation,and validation group were used for external validation.AUC was calculated and calibration curves were drawn to evaluate the prediction accuracy and consistency of the nomograms.Results:A total of 1182 RCC patients with synchronous bone metastasis were enrolled in this study cohort.The median OS of RCC patients with synchronous bone metastasis was 12 months,the 1-year,2-year,3-year,and 5-year OS rates were 50.83%,33.06%,23.19%,and 11.29%,respectively.The top six causes of death in patients with bone metastasis of RCC were: RCC related diseases,other malignant tumors,cardiovascular diseases,genitourinary system(except kidney),respiratory diseases and cerebrovascular diseases,which accounted for 86.47%,2.84%,1.87%,1.57%,1.47% and 0.69% of the total deaths,respectively.Multivariate Cox regression results showed that elder patients(40-70y: HR=1.26,95%CI: 0.75-2.12;Age?70y: HR=1.66,95%CI: 0.98-2.82,P<0.001),primary focus of the tumor in right kidney(HR=1.16,95%CI: 1.03-1.32,P=0.018),higher tumor T stage(T3: HR=1.12,95%CI:0.95-1.33;T4: HR=1.09,95%CI: 0.88-1.36,P=0.029),poor tumor grade(Grade III: HR=1.19,95%CI: 0.95-1.50;Grade IV: HR=1.29,95%CI:1.00-1.68,P=0.014),lymph node involvement(HR=1.31,95%CI: 1.13-1.51,P<0.001),brain metastasis(HR=1.41,95%CI: 1.15-1.73,P=0.001),liver metastasis(HR=1.26,95%CI: 1.05-1.51,P=0.012),lung metastasis(HR=1.54,95%CI: 1.34-1.77,P<0.001),papillary carcinoma(HR=1.54,95%CI: 1.22-1.94,P<0.001),collecting duct carcinoma(HR=1.69,95%CI: 1.03-2.79,P=0.04)were positively correlated with the prognosis of RCC patients with bone metastasis,married(HR=0.83,95%CI: 0.73-0.95,P=0.007),surgical treatment of primary lesion(HR=0.43,95%CI: 0.37-0.49,P<0.001)were negatively correlated with the prognosis.The AUC of the modeling group was 0.752(95%CI: 0.717-0.787),the 1-year and 2-year AUC of the validation group were 0.688 and 0.744,respectively.The calibration curve showed that the prediction consistency was good.Conclusions:RCC related diseases were the main cause of death in RCC patients with bone metastasis.Advanced age,unmarried,primary focus of the tumor in right kidney,higher T stage,poor tumor grade,lymph node involvement,lung metastasis,liver metastasis,brain metastasis,papillary carcinoma,collecting duct carcinoma,and primary focus without surgical treatment were all independent prognostic factors for RCC patients with bone metastasis.The prognostic nomograms can be used to predict the individualized survival probability of RCC patients with bone metastasis,and guide doctors to make individualized treatment algorithms.Part III: Baseline characteristics and prognostic factors for RCC patients with bone metastasis in Tianjin Medical University Cancer Institute and Hospital,and validation of the prognostic nomograms in Part II Objective:Based on the relevant baseline characteristics of RCC patients with bone metastasis in Tianjin Medical University Cancer Institute and Hospital,the prognostic factors of RCC patients with bone metastasis were further confirmed.Meanwhile,the prediction accuracy of RCC prognostic nomogram established in Part II was validated by single center.Methods:Data of RCC patients with synchronous bone metastasis were collected between January 1,2009 and December 31,2018 in Tianjin Medical University Cancer Institute and Hospital.The relevant demographic characteristics,clinical and pathological characteristics and treatment methods were recorded and sorted out using a standardized database.Meanwhile,the prognosis of the subjects was followed up by telephone,and the last follow-up time was December 31,2019.Univariate and multivariate COX regression analysis were used to identify the prognostic factors for RCC patients with bone metastasis in our hospital.The prognostic nomograms established in Part II were validated externally by single center.Results:A total of 153 patients with RCC patients with synchronous bone metastasis were enrolled in our hospital,including 106 males and 47 females,with an average age of 62.2 years.The median OS of RCC patients with bone metastasis was 14 months,and the 1-year and 2-year overall survival rates were 53.86% and 12.95%,respectively.Multivariate Cox regression results showed that collecting duct carcinoma(HR=5.59,95%CI: 1.09-28.66,P=0.017),lymph node involvement(HR= 2.07,95%CI: 1.26-3.42,P=0.004),liver metastasis(HR=1.95,95%CI: 1.03-3.68,P=0.040),brain metastasis(HR=1.92,95%CI: 1.06-3.48,P=0.031),lung metastasis(HR=1.74,95%CI: 1.01-2.99,P=0.046),surgical treatment of primary lesion(HR=0.56,95%CI: 0.34-0.91,P=0.020),and bone metastasis surgery(HR=0.52,95%CI: 0.30-0.88,0.016)were significantly correlated with the prognosis of RCC patients with bone metastasis.The AUC of 1-year and 2-year prediction models established in Part II of the study was 0.640 and 0.646 respectively.The calibration curve showed that the predicted survival probability of RCC patients with bone metastasis was consistent with the actual survival probability.Conclusions:The median OS of RCC patients with synchronous bone metastasis in our hospital was slightly longer.However,the overall survival rate after 1 year was low.Collecting duct carcinoma,lymph node involvement,brain metastasis,lung metastasis,liver metastasis,surgical treatment of the primary site,and surgical treatment of the bone metastasis sites were all independent prognostic factors for RCC patients with bone metastasis in our hospital.The prognostic nomogram based on SEER database was more accurate in predicting the individualized survival rate of patients with RCC patients with bone metastasis in our hospital. |
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