Genomic alterations as predictors of survival among patients within a combined cohort with clear cell renal cell carcinoma undergoing cytoreductive nephrectomy

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

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12 Scopus citations

Abstract

Purpose To establish prognostic genomic biomarkers for patients with metastatic clear cell renal cell carcinoma (ccRCC). Materials and methods 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. Results 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). Conclusions 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.

Original languageEnglish
Pages (from-to)532.e7-532.e13
JournalUrologic Oncology: Seminars and Original Investigations
Volume35
Issue number8
DOIs
StatePublished - Aug 2017
Externally publishedYes

Keywords

  • Mortality
  • Neoplasm metastasis
  • Prognosis
  • Renal cell carcinoma

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    Tennenbaum, D. M., Manley, B. J., Zabor, E., Becerra, M. F., Carlo, M. I., Casuscelli, J., Redzematovic, A., Khan, N., Arcila, M. E., Voss, M. H., Feldman, D. R., Motzer, R. J., Benfante, N. E., Coleman, J. A., Russo, P., Hsieh, J. J., & Hakimi, A. A. (2017). Genomic alterations as predictors of survival among patients within a combined cohort with clear cell renal cell carcinoma undergoing cytoreductive nephrectomy. Urologic Oncology: Seminars and Original Investigations, 35(8), 532.e7-532.e13. https://doi.org/10.1016/j.urolonc.2017.03.015