To establish prognostic genomic biomarkers for patients with metastatic clear cell renal cell carcinoma (ccRCC).
We identified 60 patients who presented with metastatic ccRCC at our institution between 2001 and 2015 and had genomic sequencing on their primary tumor. We pooled these patients with 107 other patients with the same inclusion criteria from three well-known public databases. Five commonly mutated genes were chosen for analysis: VHL, PBRM1, BAP1, SETD2, and KDM5C. Overall survival (OS) was estimated using the Kaplan-Meier method and the log-rank test was used for comparisons between groups.
Median OS in the cohort was 2.5 years. Higher Fuhrman grade was associated with decreased median OS (P<0.001). Mutations in SETD2 (P = 0.027) and KDM5C (P = 0.019) were associated with reduced risk of death (hazard ratio [HR] = 0.58 [95% CI: 0.35-0.94] and HR = 0.43 [95% CI: 0.22-0.85], respectively). BAP1 mutations (P = 0.008) were associated with increased risk of death (HR = 1.81 [95% CI: 1.16-2.83]). There were significantly more female patients with a BAP1 mutation than females in the overall cohort (P = 0.001).
Mutations in BAP1 negatively affected OS, whereas SETD2 and KDM5C mutations were associated with prolonged OS in our pooled cohort of 167 patients with metastatic ccRCC. Our results expand upon efforts at understanding genomic biomarkers in localized disease. Those efforts set the stage for our novel investigation examining associations of select recurrent somatic mutations in stage IV patients with ccRCC.
Urologic oncology. 2017 Apr 10 [Epub ahead of print]
Daniel M Tennenbaum, Brandon J Manley, Emily Zabor, Maria F Becerra, Maria I Carlo, Jozefina Casuscelli, Almedina Redzematovic, Nabeela Khan, Maria E Arcila, Martin H Voss, Darren R Feldman, Robert J Motzer, Nicole E Benfante, Jonathan A Coleman, Paul Russo, James J Hsieh, Abraham Ari Hakimi
Urology Service, Department of Surgery, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY., Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY., Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY., Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, SUNY Downstate, New York, NY., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY., Urology Service, Department of Surgery, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: .