A retrospective single-centered, comprehensive targeted genetic sequencing analysis of prognostic survival using tissues from Korean patients with metastatic renal cell carcinoma after targeted therapy.

Purpose: To identify candidate gene mutations to significantly predict the risk of survival prognosis after treatment with systemic first-line targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) patients.

Materials And Methods: Between 2005 and 2017, 168 triplet-tissue block samples from 56 mRCC patients were selected for targeted gene sequencing (TGS). Fifty-six patients' medical records including overall survival (OS) and progression-free survival (PFS) at the time of mRCC diagnosis were evaluated. The patients were grouped into favorable (>12 months/>3 years), intermediate (3-12/12-36 months), and poor groups according to their PFS/OS (<3 months/<12 months). We identified any significant therapeutic targeted genes relating to the survival with a significance at p<0.050.

Results: The first line therapeutic response showed 1.8% complete remission, 14.2% partial response, 42.9% stable disease, and 41.1% progressive disease. Among the overall TGS results, the cumulative effect of , and/or genes significantly reflected the therapeutic responses in terms of PFS/OS; and mutations were associated with poor prognostic outcomes (p<0.050). Among only triplet-quality check passed tissues, the , , , and mutated genes significantly correlated with OS. Regarding metastasis, patients with liver metastasis had the worst OS (p=0.050). The combinational mutation number from these two candidate genes in the liver metastatic samples with mutated and also showed a significantly worse OS than those with other metastatic lesions (p<0.050).

Conclusions: This study reports several significant mutated genes related to the survival prognosis in mRCC patients treated with first-line TT.