title: Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy.
abstract: OBJECTIVE
  The optimal timing of postoperative radiotherapy (RT) after radical prostatectomy (RP) is unclear. We hypothesized that a genomic classifier (GC) would provide prognostic and predictive insight into the development of clinical metastases in men receiving post-RP RT and inform decision making.
  
  
  METHODS
  GC scores were calculated from 188 patients with pT3 or margin-positive prostate cancer, who received post-RP RT at Thomas Jefferson University and Mayo Clinic between 1990 and 2009. The primary end point was clinical metastasis. Prognostic accuracy of the models was tested using the concordance index for censored data and decision curve analysis. Cox regression analysis tested the relationship between GC and metastasis.
  
  
  RESULTS
  The cumulative incidence of metastasis at 5 years after RT was 0%, 9%, and 29% for low, average, and high GC scores, respectively (P = .002). In multivariable analysis, GC and pre-RP prostate-specific antigen were independent predictors of metastasis (both P < .01). Within the low GC score (< 0.4), there were no differences in the cumulative incidence of metastasis comparing patients who received adjuvant or salvage RT (P = .79). However, for patients with higher GC scores (≥ 0.4), cumulative incidence of metastasis at 5 years was 6% for patients treated with adjuvant RT compared with 23% for patients treated with salvage RT (P < .01).
  
  
  CONCLUSIONS
  In patients treated with post-RP RT, GC is prognostic for the development of clinical metastasis beyond routine clinical and pathologic features. Although preliminary, patients with low GC scores are best treated with salvage RT, whereas those with high GC scores benefit from adjuvant therapy. These findings provide the first rational selection of timing for post-RP RT.
authors: Robert B. Den, Edouard J. Trabulsi, Adam P. Dicker, Costas D. Lallas, and Leonard G. Gomella, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit; Felix Y. Feng, University of Michigan, Ann Arbor, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; and Kasra Yousefi, Voleak Choeurng, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada. Robert.Den@jefferson.edu.
authors: Robert B
authors: RB
authors: Den
authors: Robert B. Den, Edouard J. Trabulsi, Adam P. Dicker, Costas D. Lallas, and Leonard G. Gomella, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit; Felix Y. Feng, University of Michigan, Ann Arbor, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; and Kasra Yousefi, Voleak Choeurng, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Kasra
authors: K
authors: Yousefi
authors: Robert B. Den, Edouard J. Trabulsi, Adam P. Dicker, Costas D. Lallas, and Leonard G. Gomella, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit; Felix Y. Feng, University of Michigan, Ann Arbor, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; and Kasra Yousefi, Voleak Choeurng, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Edouard J
authors: EJ
authors: Trabulsi
authors: Robert B. Den, Edouard J. Trabulsi, Adam P. Dicker, Costas D. Lallas, and Leonard G. Gomella, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit; Felix Y. Feng, University of Michigan, Ann Arbor, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; and Kasra Yousefi, Voleak Choeurng, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Firas
authors: F
authors: Abdollah
authors: Robert B. Den, Edouard J. Trabulsi, Adam P. Dicker, Costas D. Lallas, and Leonard G. Gomella, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit; Felix Y. Feng, University of Michigan, Ann Arbor, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; and Kasra Yousefi, Voleak Choeurng, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Voleak
authors: V
authors: Choeurng
authors: Robert B. Den, Edouard J. Trabulsi, Adam P. Dicker, Costas D. Lallas, and Leonard G. Gomella, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit; Felix Y. Feng, University of Michigan, Ann Arbor, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; and Kasra Yousefi, Voleak Choeurng, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Felix Y
authors: FY
authors: Feng
authors: Robert B. Den, Edouard J. Trabulsi, Adam P. Dicker, Costas D. Lallas, and Leonard G. Gomella, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit; Felix Y. Feng, University of Michigan, Ann Arbor, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; and Kasra Yousefi, Voleak Choeurng, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Adam P
authors: AP
authors: Dicker
authors: Robert B. Den, Edouard J. Trabulsi, Adam P. Dicker, Costas D. Lallas, and Leonard G. Gomella, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit; Felix Y. Feng, University of Michigan, Ann Arbor, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; and Kasra Yousefi, Voleak Choeurng, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Costas D
authors: CD
authors: Lallas
authors: Robert B. Den, Edouard J. Trabulsi, Adam P. Dicker, Costas D. Lallas, and Leonard G. Gomella, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit; Felix Y. Feng, University of Michigan, Ann Arbor, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; and Kasra Yousefi, Voleak Choeurng, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Leonard G
authors: LG
authors: Gomella
authors: Robert B. Den, Edouard J. Trabulsi, Adam P. Dicker, Costas D. Lallas, and Leonard G. Gomella, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit; Felix Y. Feng, University of Michigan, Ann Arbor, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; and Kasra Yousefi, Voleak Choeurng, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Elai
authors: E
authors: Davicioni
authors: Robert B. Den, Edouard J. Trabulsi, Adam P. Dicker, Costas D. Lallas, and Leonard G. Gomella, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit; Felix Y. Feng, University of Michigan, Ann Arbor, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; and Kasra Yousefi, Voleak Choeurng, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: R Jeffrey
authors: RJ
authors: Karnes
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003657:Decision Making; D023281:Genomics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049451:Nomograms; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000532:radiotherapy* / Q000601:surgery*; D018714:Radiotherapy, Adjuvant / Q000379:methods*; D012044:Regression Analysis; D018570:Risk Assessment; D016879:Salvage Therapy; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen