Genomic prostate cancer classifier predicts biochemical failure and metastases in patients after postoperative radiation therapy

Abstract

Purpose: To test the hypothesis that a genomic classifier (GC) would predict biochemical failure (BF) and distant metastasis (DM) in men receiving radiation therapy (RT) after radical prostatectomy (RP).

Methods and materials: Among patients who underwent post-RP RT, 139 were identified for pT3 or positive margin, who did not receive neoadjuvant hormones and had paraffin-embedded specimens. Ribonucleic acid was extracted from the highest Gleason grade focus and applied to a high-density-oligonucleotide microarray. Receiver operating characteristic, calibration, cumulative incidence, and Cox regression analyses were performed to assess GC performance for predicting BF and DM after post-RP RT in comparison with clinical nomograms.

Results: The area under the receiver operating characteristic curve of the Stephenson model was 0.70 for both BF and DM, with addition of GC significantly improving area under the receiver operating characteristic curve to 0.78 and 0.80, respectively. Stratified by GC risk groups, 8-year cumulative incidence was 21%, 48%, and 81% for BF (P<.0001) and for DM was 0, 12%, and 17% (P=.032) for low, intermediate, and high GC, respectively. In multivariable analysis, patients with high GC had a hazard ratio of 8.1 and 14.3 for BF and DM. In patients with intermediate or high GC, those irradiated with undetectable prostate-specific antigen (PSA ≤0.2 ng/mL) had median BF survival of >8 years, compared with <4 years for patients with detectable PSA (>0.2 ng/mL) before initiation of RT. At 8 years, the DM cumulative incidence for patients with high GC and RT with undetectable PSA was 3%, compared with 23% with detectable PSA (P=.03). No outcome differences were observed for low GC between the treatment groups.

Conclusion: The GC predicted BF and metastasis after post-RP irradiation. Patients with lower GC risk may benefit from delayed RT, as opposed to those with higher GC; however, this needs prospective validation. Genomic-based models may be useful for improved decision-making for treatment of high-risk prostate cancer.

Conflict of interest statement

Conflict of interest: M.G., K.Y., and E.D. are employees of GenomeDx Biosciences. R.B.D., F.Y.F., and T.N.S. have received unrestricted research grants from GenomeDx.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1

Area under the receiver operating characteristic curve (AUC): comparison of genomic classifier (GC)-based and clinical-only risk models for predicting biochemical failure (A) and distant metastasis (B) after postoperative radiation therapy. CAPRA-S = cancer of the prostate risk assessment post-surgical score; CI = confidence interval.

Fig. 2

Cumulative incidence plots of biochemical failure (A) and distant metastasis (B) for low-, intermediate-, and high-risk genomic classifier (GC) score groups. Cut points were reported previously (29).

Fig. 3

Cumulative incidence plots of biochemical failure and distant metastasis comparing patients treated with radiation therapy (RT) when prostate-specific antigen (PSA) was undetectable (A, C) and detectable (B, D), as stratified by genomic classifier (GC) score risk groups.