A genomic classifier predicting metastatic disease progression in men with biochemical recurrence after prostatectomy

Abstract

Background: Due to their varied outcomes, men with biochemical recurrence (BCR) following radical prostatectomy (RP) present a management dilemma. Here, we evaluate Decipher, a genomic classifier (GC), for its ability to predict metastasis following BCR.

Methods: The study population included 85 clinically high-risk patients who developed BCR after RP. Time-dependent receiver operating characteristic (ROC) curves, weighted Cox proportional hazard models and decision curves were used to compare GC scores to Gleason score (GS), PSA doubling time (PSAdT), time to BCR (ttBCR), the Stephenson nomogram and CAPRA-S for predicting metastatic disease progression. All tests were two-sided with a type I error probability of 5%.

Results: GC scores stratified men with BCR into those who would or would not develop metastasis (8% of patients with low versus 40% with high scores developed metastasis, P<0.001). The area under the curve for predicting metastasis after BCR was 0.82 (95% CI, 0.76-0.86) for GC, compared to GS 0.64 (0.58-0.70), PSAdT 0.69 (0.61-0.77) and ttBCR 0.52 (0.46-0.59). Decision curve analysis showed that GC scores had a higher overall net benefit compared to models based solely on clinicopathologic features. In multivariable modeling with clinicopathologic variables, GC score was the only significant predictor of metastasis (P=0.003).

Conclusions: When compared to clinicopathologic variables, GC better predicted metastatic progression among this cohort of men with BCR following RP. While confirmatory studies are needed, these results suggest that use of GC may allow for better selection of men requiring earlier initiation of treatment at the time of BCR.

Conflict of interest statement

CONFLICT OF INTEREST

Mercedeh Ghadessi, Nicholas Erho, Anamaria Crisan, Christine Buerki, and Ismael A Vergara are employees of GenomeDx Biosciences. Darby J S Thompson is a consultant for GenomeDx Biosciences. Timothy J Triche and Elai Davicioni are founders of GenomeDx Biosciences. The remaining authors declare no conflict of interest.

Figures

Figure 1

Influence of genomic classifier (GC) score on metastatic progression in patients with biochemical recurrence (BCR) following radical prostatectomy. (a) Box plots demonstrating the distribution of GC among patients who progressed to metastasis following BCR (mets) versus those who did not. (b) Cumulative incidence of clinical metastasis based on GC risk groups.

Figure 2

Receiver operating characteristic (ROC) curve analysis comparing genomic classifier (GC) with (a) individual clinicopathologic factors and (b) clinical models and genomic-clinical models for predicting clinical metastasis at 3 years post biochemical recurrence (BCR). AUC, area under the ROC curve; ECE, extra-capsular extension; GS, Gleason score; SM, surgical margin; SVI, seminal vesicle invasion.

Figure 3

Decision curve analysis comparing the net benefit of genomic classifier (GC) with clinical-only models.