Validation of a Genomic Classifier for Prediction of Metastasis Following Postoperative Salvage Radiation Therapy


      Most men who develop elevated prostate-specific antigen (PSA) level recurrence postprostatectomy are treated with salvage radiation therapy (SRT). However, since PSA recurrence is a poor surrogate for metastatic disease, it is unclear which men may benefit from a more aggressive approach (i.e., incorporation of hormonal therapy). We hypothesized that a genomic classifier (GC), a validated predictor of metastasis, would distinguish those patients for whom additional therapy is beneficial from those for whom SRT on its own is likely insufficient.


      Genomic classifier (GC) scores were calculated from 166 prostate cancer patients who received SRT at Thomas Jefferson University, Veteran Affairs Medical Center Durham, and Mayo Clinic, between 1990 and 2010. SRT was defined as the administration of RT with pre-RT PSA levels >0.2 ng/mL. GC and Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scores were compared using survival c-index, competing-risks, and Cox regression analysis for the prediction of metastasis.


      Survival c-index for predicting metastasis 5 years post-SRT was 0.87 (95% CI: 0.73–0.90) for GC and 0.62 (95% CI: 0.48–0.77) for CAPRA-S. The cumulative incidence of metastasis at 5 years post-SRT was 2.8%, 5.8%, and 33.5% for low, average, and high GC scores (P < .0001) and 17%, 2.3%, and 15% for low, average, and high CAPRA-S scores (P = .19). In univariable analysis only GC, extraprostatic extension, and pre-RT PSA were significant predictors of metastasis. In multivariable analyses with clinical risk factors or the CAPRA-S nomogram, GC was the only independent predictor of metastasis with an HR of 1.59 (1.17–2.16, P = .0017) for a 10% unit increase in risk score.


      In patients treated with postoperative SRT for PSA recurrence, GC is a powerful predictor of metastasis. Patients with low GC scores have an excellent prognosis with SRT and may avoid concurrent hormonal therapy. Patients with a high GC risk are at highest risk for metastatic disease and SRT failure and may benefit from intensified systemic therapy.


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