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

ABSTRACT: ABSTACT:BACKGROUND: Many 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. METHODS:Decipher 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). RESULTS:Decipher from prostatectomies was significantly associated with adverse pathologic features (p-values?

SUBMITTER: Kim HL

PROVIDER: S-EPMC6760567 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Kim Hyung L HL Li Ping P Huang Huei-Chung HC Deheshi Samineh S Marti Tara T Knudsen Beatrice B Abou-Ouf Hatem H Alam Ridwan R Lotan Tamara L TL Lam Lucia L C LLC du Plessis Marguerite M Davicioni Elai E Fleshner Neil N Lane Brian R BR Ross Ashley E AE Davis John W JW Mohler James L JL Trock Bruce J BJ Klein Eric A EA Tosoian Jeffrey J JJ Hyndman M Eric ME Bismar Tarek A TA

Prostate cancer and prostatic diseases 20181212 3

<h4>Abstact</h4>BACKGROUND: Many 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.<h4>Methods</h4>Decipher was initially assessed in a prospective cohort of prostatectomies to explore the correlation with clinically meaningful biologic characteristics a ...[more]

PMID: 30542054

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Project description:PurposeTo determine whether multiparametric magnetic resonance (MR) imaging can help identify patients with prostate cancer who would most appropriately be candidates for active surveillance (AS) according to current guidelines and to compare the results with those of conventional clinical assessment scoring systems, including the D'Amico, Epstein, and Cancer of the Prostate Risk Assessment (CAPRA) systems, on the basis of findings at prostatectomy.Materials and methodsThis institutional review board-approved HIPAA-compliant retrospectively designed study included 133 patients (mean age, 59.3 years) with a mean prostate-specific antigen level of 6.73 ng/mL (median, 4.39 ng/mL) who underwent multiparametric MR imaging at 3.0 T before radical prostatectomy. Informed consent was obtained from all patients. Patients were then retrospectively classified as to whether they would have met AS eligibility criteria or were better served by surgery. AS eligibility criteria for prostatectomy specimens were a dominant tumor smaller than 0.5 mL without Gleason 4 or 5 patterns or extracapsular or seminal vesicle invasion. Conventional clinical assessment scores (the D'Amico, Epstein, and CAPRA scoring systems) were compared with multiparametric MR imaging findings for predicting AS candidates. The level of significance of difference between scoring systems was determined by using the χ(2) test for categoric variables with the level of significance set at P < .05.ResultsAmong 133 patients, 14 were eligible for AS on the basis of prostatectomy results. The sensitivity, positive predictive value (PPV), and overall accuracy, respectively, were 93%, 25%, and 70% for the D'Amico system, 64%, 45%, and 88% for the Epstein criteria, and 93%, 20%, and 59% for the CAPRA scoring system for predicting AS candidates (P < .005 for all, χ(2) test), while multiparametric MR imaging had a sensitivity of 93%, a PPV of 57%, and an overall accuracy of 92% (P < .005).ConclusionMultiparametric MR imaging provides useful additional information to existing clinicopathologic scoring systems of prostate cancer and improves the assignment of treatment (eg, AS or active treatment).

Project description:Objective• To assess whether the carrier status of 35 risk alleles for prostate cancer (CaP) is associated with having unfavourable pathological features in the radical prostatectomy specimen in men with clinically low risk CaP who fulfil commonly accepted criteria as candidates for active surveillance.Patients and methods• We studied men of European ancestry with CaP who fulfilled the commonly accepted clinical criteria for active surveillance (T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason ?6, three or fewer positive cores, ?50% tumour involvement/core) but instead underwent early radical prostatectomy. • We genotyped these men for 35 CaP risk alleles. We defined 'unfavourable' pathological characteristics to be Gleason ?7 and/or ? pT2b in their radical prostatectomy specimen.Results• In all, 263 men (median age 60 [46-72] years) fulfilled our selection criteria for active surveillance, and 58 of 263 (22.1%) were found to have 'unfavourable' pathological characteristics. • The frequencies of three CaP risk alleles (rs1447295 [8q24], P= 0.004; rs1571801 [9q33.2], P= 0.03; rs11228565 [11q13], P= 0.02) were significantly higher in men with 'unfavourable' pathological characteristics. • Two other risk alleles were proportionately more frequent (rs10934853 [3q21], P= 0.06; rs1859962 [17q24], P= 0.07) but did not achieve nominal statistical significance. • Carriers of any one of the significantly over-represented risk alleles had twice the likelihood of unfavourable tumour features (P= 0.03), and carriers of any two had a sevenfold increased likelihood (P= 0.001). • Receiver-operator curve analysis demonstrated an area under the curve of 0.66, suggesting that the number of single nucleotide polymorphisms carried provided discrimination between men with 'favourable' and 'unfavourable' tumour features in their prostatectomy specimen.Conclusion• In potential candidates for active surveillance, certain CaP risk alleles are more prevalent in patients with 'unfavourable' pathological characteristics in their radical prostatectomy specimen.

Dataset Information

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

Publications

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

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