Genomic predictors of survival in patients with high-grade urothelial carcinoma of the bladder Journal Article


Authors: Kim, P. H.; Cha, E. K.; Sfakianos, J. P.; Iyer, G.; Zabor, E. C.; Scott, S. N.; Ostrovnaya, I.; Ramirez, R.; Sun, A.; Shah, R.; Yee, A. M.; Reuter, V. E.; Bajorin, D. F.; Rosenberg, J. E.; Schultz, N.; Berger, M. F.; Al-Ahmadie, H. A.; Solit, D. B.; Bochner, B. H.
Article Title: Genomic predictors of survival in patients with high-grade urothelial carcinoma of the bladder
Abstract: Urothelial carcinoma of the bladder (UCB) is genomically heterogeneous, with frequent alterations in genes regulating chromatin state, cell cycle control, and receptor kinase signaling. To identify prognostic genomic markers in high-grade UCB, we used capture-based massively parallel sequencing to analyze 109 tumors. Mutations were detected in 240 genes, with 23 genes mutated in ≥5% of cases. The presence of a recurrent phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation was associated with improved recurrence-free survival (RFS) (hazard ratio [HR]: 0.35; p = 0.014) and improved cancer-specific survival (CSS) (HR: 0.35; p = 0.040) in patients treated with radical cystectomy (RC). In multivariable analyses controlling for pT and pN stages, PIK3CA mutation remained associated with RFS (HR: 0.39; p = 0.032). The most frequent alteration, TP53 mutation (57%), was more common in extravesical disease (69% vs 32%, p = 0.005) and lymph node-positive disease (77% vs 56%, p = 0.025). Patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-Altered tumors experienced worse RFS (HR: 5.76; p < 0.001) and worse CSS (HR: 2.94; p = 0.029) in multivariable analyses. Mutations in chromatin-modifying genes were highly prevalent but not associated with outcomes. In UCB patients treated with RC, PIK3CA mutations are associated with favorable outcomes, whereas TP53 and CDKN2A alterations are associated with poor outcomes. Genomic profiling may aid in the identification of UCB patients at highest risk following RC. Patient summary Using next-generation sequencing, we identified genomic subsets of high-grade urothelial bladder cancer associated with favorable and unfavorable outcomes. These findings may aid in the selection of patients most likely to benefit from novel combined modality approaches.
Keywords: mutation; bladder cancer; genomics; pik3ca; clinical outcomes
Journal Title: European Urology
Volume: 67
Issue: 2
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2014-02-01
Start Page: 198
End Page: 201
Language: English
DOI: 10.1016/j.eururo.2014.06.050
PROVIDER: scopus
PMCID: PMC4312739
PUBMED: 25092538
DOI/URL:
Notes: Export Date: 2 February 2015 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Dean Bajorin
    382 Bajorin
  2. David Solit
    420 Solit
  3. Gopakumar Vasudeva Iyer
    121 Iyer
  4. Emily Craig Zabor
    119 Zabor
  5. Bernard Bochner
    315 Bochner
  6. Michael Forman Berger
    373 Berger
  7. Victor Reuter
    890 Reuter
  8. Philip Hyunwoo Kim
    39 Kim
  9. Nikolaus D Schultz
    193 Schultz
  10. Jonathan Eric Rosenberg
    210 Rosenberg
  11. Arony Jessica Sun
    5 Sun
  12. Ronak Hasmukh Shah
    42 Shah
  13. Sasinya Neka Scott
    66 Scott
  14. Alyssa Mae Yee
    3 Yee
  15. Ricardo   Ramirez
    19 Ramirez
  16. Eugene K. Cha
    56 Cha