External Validation of the MSKCC and IMDC Risk Models in Patients Treated with Targeted Therapy as a First-line and Subsequent Second-line Treatment: A Japanese Multi-institutional Study

Background Two risk models, the Memorial Sloan Kettering Cancer Center (MSKCC) model and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, have been studied in metastatic renal cell carcinoma (mRCC) treated with targeted therapy. Objective To validate externally the predictive accuracies of the MSKCC and IMDC models for prognosis in mRCC patients treated with first-line and subsequent second-line targeted therapy. Design, setting, and participants A total of 311 patients were assessed retrospectively. Intervention All patients underwent targeted therapy. Outcome measurements and statistical analysis Survival outcomes were assessed using Kaplan-Meier analysis. The predictive ability was evaluated using the c-index. Results and limitations Regarding to the first-line targeted therapy, the 3-yr overall survival (OS) rates of the MSKCC (p < 0.001) and IMDC models (p < 0.001) were 76.2% and 77.3%, respectively, in the favorable-risk group; 46.7% and 47.9%, respectively, in the intermediate-risk group; and 13.4% and 15.6%, respectively, in the poor-risk group. The c-indexes were 0.68 for the MSKCC model and 0.69 for the IMDC model in a first-line setting. Regarding the second-line targeted therapy, the 1-yr OS rates of the MSKCC (p < 0.001) and IMDC models (p < 0.001) were 80.9% and 90.5%, respectively, in the favorable-risk group; 71.4% and 70.6%, respectively, in the intermediate-risk group; and 31.7% and 24.6%, respectively, in the poor-risk group. The c-indexes were 0.66 for the MSKCC model and 0.65 for the IMDC model in the second-line setting. The study is limited by its retrospective nature. Conclusions The results may assist physicians in providing more appropriate patient counseling and imply the need for a future prognostic tool in mRCC treated with targeted therapy. Patient summary Both risk models were useful for the risk stratification in metastatic renal cell carcinoma (mRCC) patients treated with first-line and second-line targeted therapy; however, it might be necessary to further update or optimize the models for our Japanese cohort of mRCC patients.