Validation of a Genomic Classifier that Predicts Metastasis Following Radical Prostatectomy in an at Risk Patient Population
Year of Publication
Karnes, R; Bergstralh, E; Davicioni, E; Ghadessi, M; Buerki, C; Mitra, A; Crisan, A; Erho, Ni; Vergara, I; Lam, LL; Carlson, R; Thompson, DJS; Haddad, Z; Zimmerman, B; Sierocinski, T; Triche, TJ; Kollmeyer, T; Ballman, KV; Black, P; Klee, G; Jenkins, R
biochemical recurrence; clinical only classifier; extracapsular extension; metastasis; noncoding RNA; prostate cancer; prostate specific antigen; prostatic neoplasms; radical prostatectomy; seminal vesicle invasion; transcriptome analysis
PURPOSE: Prostate cancer patients with locally advanced disease after radical prostatectomy (RP) are candidates for secondary therapy. However, this higher risk population is heterogeneous and many will not metastasize even when conservatively managed. Given the limited specificity of pathologic features to predict metastasis, newer risk-prediction models are needed. This represents a validation study of a genomic classifier (GC) that predicts post-RP metastasis in a high-risk population. MATERIALS AND METHODS: A case-cohort design was used to sample 1,010 post-RP patients at high risk of recurrence treated between 2000-2006. Patients had preoperative PSA >20 ng/mL, Gleason ≥8, pT3b or GPSM score ≥10. Patients with metastasis at diagnosis or any prior treatment for prostate cancer were excluded. 20% random sampling created a subcohort that included all cases with metastasis. 22-marker GC scores were generated for 219 patients with available genomic data. Receiver operating characteristic and decision curves, competing risk, and weighted regression models assessed GC performance. RESULTS: GC had area under the curve of 0.79 for predicting 5-year metastasis post-RP. Decision curves showed that net benefit of GC exceeded clinical-only models. GC was the predominant predictor of metastasis in multivariable analysis. Cumulative incidence of metastasis at 5 years post-RP was 2.4%, 6.0% and 22.5% for patients with low (60% of patients), intermediate (21% of patients), and high (19% of patients) GC scores, respectively (p<0.001). CONCLUSIONS: These results indicate that genomic information from the primary tumor can identify patients with adverse pathology who are most at risk for metastasis and potentially lethal prostate cancer.