Validation of the Decipher Test for predicting adverse pathology in candidates for prostate cancer active surveillance

Abstract

AbstactBackgroundMany men diagnosed with prostate cancer are active surveillance (AS) candidates. However, AS may be associated with increased risk of disease progression and metastasis due to delayed therapy. Genomic classifiers, e.g., Decipher, may allow better risk-stratify newly diagnosed prostate cancers for AS.MethodsDecipher was initially assessed in a prospective cohort of prostatectomies to explore the correlation with clinically meaningful biologic characteristics and then assessed in diagnostic biopsies from a retrospective multicenter cohort of 266 men with National Comprehensive Cancer Network (NCCN) very low/low and favorable-intermediate risk prostate cancer. Decipher and Cancer of the Prostate Risk Assessment (CAPRA) were compared as predictors of adverse pathology (AP) for which there is universal agreement that patients with long life-expectancy are not suitable candidates for AS (primary pattern 4 or 5, advanced local stage [pT3b or greater] or lymph node involvement).ResultsDecipher from prostatectomies was significantly associated with adverse pathologic features (p-values < 0.001). Decipher from the 266 diagnostic biopsies (64.7% NCCN-very-low/low and 35.3% favorable-intermediate) was an independent predictor of AP (odds ratio 1.29 per 10% increase, 95% confidence interval [CI] 1.03–1.61, p-value 0.025) when adjusting for CAPRA. CAPRA area under curve (AUC) was 0.57, (95% CI 0.47–0.68). Adding Decipher to CAPRA increased the AUC to 0.65 (95% CI 0.58–0.70). NPV, which determines the degree of confidence in the absence of AP for patients, was 91% (95% CI 87–94%) and 96% (95% CI 90–99%) for Decipher thresholds of 0.45 and 0.2, respectively. Using a threshold of 0.2, Decipher was a significant predictor of AP when adjusting for CAPRA (p-value 0.016).ConclusionDecipher can be applied to prostate biopsies from NCCN-very-low/low and favorable-intermediate risk patients to predict absence of adverse pathologic features. These patients are predicted to be good candidates for active surveillance.

Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

“…Retrospective case cohort studies have shown that these assays provide prognostic information independent of NCCN or CAPRA risk groups, which include likelihood of death with conservative management, likelihood of biochemical recurrence after radical prostatectomy or EBRT, likelihood of adverse pathologic features after radical prostatectomy, and likelihood of developing metastasis after operation or salvage EBRT. [131][132][133][134][135][136][137][138][139][140] A prospective, clinical utility study of 3,966 patients newly diagnosed with localized prostate cancer found that the rates of active surveillance increased with use of a tissue-based gene expression classifier. 141 Active surveillance rates were 46.2%, 75.9%, and 57.9% for those whose classifier results were above the specified threshold, below the threshold, and those who did not undergo genomic testing, respectively (P,.001).…”

Low Abundance of Circulating Tumor DNA in Localized Prostate Cancer

“…Over the last two decades, prostate cancer remains the most diagnosed neoplasm in American men, representing approximately 20% of all new diagnoses in 2019 [1]. Overtreatment of newlydiagnosed, indolent prostate cancers detected by rising levels of prostate-specific antigen (PSA) has been mitigated by increasingly widespread adoption of active surveillance, MRI-targeted biopsies, nomograms, and molecular tests for assessing the risk posed by unsampled higher grade disease [2][3][4][5]. While the absence of adverse pathological features, such as high Gleason score or seminal vesicle invasion, from biopsy is associated with improved outcomes following definitive therapy (surgery or radiation), sampling errors may lead to underestimation of the risk of biochemical recurrence.…”

Decipher identifies men with otherwise clinically favorable-intermediate risk disease who may not be good candidates for active surveillance

“…The primary objective was to evaluate Decipher's prognostic ability to predict AP (defined as GG 3−5, pT3b or higher, or lymph node invasion (LNI) [14]) at RP within the NCCN F-IR group while accounting for clinical risk using the linear, extensively validated Cancer of the Prostate Risk Assessment (CAPRA [16]) score. In addition to this definition of AP, we also evaluated two alternatives: (1) GG 3−5 as an isolated endpoint, and (2) expanding the definition of adverse pathology to include extraprostatic extension (i.e., GG 3−5, ≥pT3a, or LNI (AP-II)).…”

“…Specimen collection and sample processing were conducted as described previously [13,14]. The prostate needle biopsy core with highest grade and percentage of core involved with tumor was sampled for the Decipher assay, a CAP/CLIA clinical-grade whole-transcriptome assay.…”