Inherent characteristics of metachronous metastatic renal cell carcinoma in the era of targeted agents

Background: To assess the prognostic and predictive factors of time to treatment failure (TTF) and overall survival (OS), respectively, in patients with metachronous metastatic renal cell carcinoma (mRCC) who were treated with targeted agents. Materials and Methods: We retrospectively reviewed metachronous mRCC patients, defined as individuals diagnosed with metastatic disease > 3 months after initial nephrectomy, treated at an institute since 2005. Cox proportional hazard regression analysis was performed to discover the most determinant variables associated with TTF and OS. Results: Sarcomatoid features, absence of metastasectomy, multiple site metastasis, time to metastasis < 1.5 year, and increased corrected calcium were independent prognostic factors of OS. The low risk group (0-1 risk factors) did not reach the median OS, whereas the OS for the intermediate (2 risk factors) and high risk groups (3-5 risk factors) were 58.6 and 23.6 months, respectively (p < 0.001). When a death event was considered the dependent factor, the area under the receiver operating characteristic curve was significantly higher than in the existing International mRCC Database Consortium (IMDC; p=0.010) and Memorial Sloan Kettering Cancer Center (MSKCC; p=0.010) risk criteria models. Conclusion: Initial tumor size or T stage did not affect TTF or OS. Patients who could not undergo metastasectomy and rapidly developed multiple metastases with higher corrected calcium and initial tumors with sarcomatoid features were less likely to benefit from targeted therapy; thus, the new agents under development or clinical trials could be more helpful than the use of standard targeted agents.