Validation of a Metastatic Assay using biopsies to improve risk stratification in patients with prostate cancer treated with radical radiation therapy
| Autor: | Richard D. Kennedy, Ciara Lyons, Christopher Steele, Darren M. Mitchell, Brendan Pang, Sean O. Hynes, Stephen McQuaid, D.A. Loblaw, Kevin M. Prise, Denis Paul Harkin, Darragh G. McArt, Viktor Berge, Suneil Jain, David Waugh, Betina Katz, Jacqueline James, Joe M. O'Sullivan, Laura A. Knight, Andrena McCavigan, Declan O'Rourke, Steven Walker, Paul Wallace Medlow, Simon S. McDade, Gemma E Logan, Ian G. Mills |
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| Přispěvatelé: | Jain, S, Lyons, CA, Walker, SM, McQuaid, S, Waugh, DJ |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Oncology Biopsy medicine.medical_treatment dose-escalation risk stratification Kaplan-Meier Estimate Androgen suppression radiation therapy Cohort Studies Androgen deprivation therapy Prostate cancer 0302 clinical medicine Urogenital Tumors Risk Factors Prostate Neoplasm Metastasis androgen suppression medicine.diagnostic_test Hematology trial Middle Aged prostate cancer metastatic medicine.anatomical_structure 030220 oncology & carcinogenesis Cohort biomarker medicine.medical_specialty Concordance men Risk Assessment Disease-Free Survival 03 medical and health sciences Internal medicine intermediate Journal Article medicine Humans radiotherapy Aged Neoplasm Staging Proportional Hazards Models Retrospective Studies business.industry Gene Expression Profiling Prostatic Neoplasms Reproducibility of Results Original Articles medicine.disease Radiation therapy Editor's Choice 030104 developmental biology recommendations paraffin-embedded tissue business prognostic |
| Zdroj: | Annals of Oncology Jain, S, Lyons, C A, Walker, S M, McQuaid, S, Hynes, S, Mitchell, D, Pang, B, Logan, G E, McCavigan, A M, O'Rourke, D, McArt, D, McDade, S, Mills, I, Prise, K M, Knight, L A, Steele, C J, Medlow, P W, Berge, V, Katz, B, Loblaw, D A, Harkin, D P, James, J, O'Sullivan, J M, Kennedy, R D & Waugh, D J 2017, ' Validation of a Metastatic Assay using biopsies to improve risk stratification in patients with prostate cancer treated with radical radiation therapy ' Annals of Oncology . DOI: 10.1093/annonc/mdx637 |
| ISSN: | 1569-8041 0923-7534 |
| Popis: | Background Radiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however,>30% of patients relapse within 5 years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Patients and methods A bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold before further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis-free survival (MFS). Results Gene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients [HR¼3.21 (1.35–7.67); P¼0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR¼2.71 (1.11–6.63); P¼0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR¼3.23 (1.22–8.59); P¼0.019] whilst CAPRA itself was not significant [HR¼1.88, (0.52–6.77); P¼0.332]. A high concordance [100% (61.5–100)] for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance. Conclusions The Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource. |
| Databáze: | OpenAIRE |
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