Impact of Systemic Therapy in Metastatic Renal-Cell Carcinoma Patients With Synchronous and Metachronous Brain Metastases

The prognosis of metastatic renal-cell carcinoma patients with brain metastases has significantly improved over the past 5 to 10 years. Through modern radiation techniques, the ability to achieve effective intracranial disease control has also improved. However, there remains a paucity of evidence characterizing the impact of systemic therapy in controlling extracranial disease in the setting of aggressive intracranial management. Background: Modern radiation techniques have led to significant improvements in intracranial disease control and overall survival (OS) for metastatic renal-cell carcinoma (mRCC) patients diagnosed with brain metastases (BM). The impact of systemic therapy in patients developing mRCC BM remains undercharacterized. Patients and Methods: We performed a retrospective cohort study of mRCC patients diagnosed with BM. Patients were grouped as having either metachronous BM (ie, >= 3 months from mRCC diagnosis) or synchronous BM (ie, < 3 months from mRCC diagnosis). Details of patient demographics, BM, systemic therapy, and outcomes were extracted. Statistical analysis comprised chi-square tests, analysis of variance, and Kaplan-Meier method to characterize survival outcomes. Results: Seventy-four patients were identified (40 at >= 3 months from mRCC diagnosis and 34 at < 3 months from mRCC diagnosis) of which 72 (97%) received local therapy for their BM. Median (interquartile range [IQR]) duration while first line treatment was longer at 7.8 (3.6-17.0) versus 5.1 (3.3-12.6) in patients with metachronous BM versus patients with synchronous BM (P = 0.6), respectively. After BM diagnosis, the metachronous BM cohort continued to receive the same systemic therapy for a median (IQR) duration of 1.9 (0.4-5.5) months, with eventual change most commonly the result of extracranial disease progression. Median (IQR) OS from mRCC diagnosis favored metachronous BM patients versus synchronous BM patients, at 64.2 (31.4-not yet reached) versus 22.4 (9.7-34.1) months (P = .003), respectively. However, this was not significantly different from the time of BM diagnosis, with median (IQR) survival of 20.6 (9.2-31.2) versus 15.7 (11.6-not yet reached) months (P = .95), respectively. Conclusion: Prolonged OS was found for mRCC patients with BM that presented either metachronously or synchronously. For patients diagnosed with metachronous BM, the development of BM may be an early sign of systemic therapy failure.