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dc.contributor.authorJain, S
dc.contributor.authorLyons, C A
dc.contributor.authorWalker, S M
dc.contributor.authorMcQuaid, S
dc.contributor.authorHynes, S O
dc.contributor.authorMitchell, D M
dc.contributor.authorPang, B
dc.contributor.authorLogan, G E
dc.contributor.authorMcCavigan, A M
dc.contributor.authorO’Rourke, D
dc.contributor.authorMcArt, D G
dc.contributor.authorMcDade, S S
dc.contributor.authorMills, I G
dc.contributor.authorPrise, K M
dc.contributor.authorKnight, L A
dc.contributor.authorSteele, C J
dc.contributor.authorMedlow, P W
dc.contributor.authorBerge, V
dc.contributor.authorKatz, B
dc.contributor.authorLoblaw, D A
dc.contributor.authorHarkin, D P
dc.contributor.authorJames, J A
dc.contributor.authorO’Sullivan, J M
dc.contributor.authorKennedy, R D
dc.contributor.authorWaugh, D J
dc.date.accessioned2018-09-20T16:11:54Z
dc.date.available2018-09-20T16:11:54Z
dc.date.issued2017-10-10
dc.identifier.citationJain, S; Lyons, C A; Walker, S M; McQuaid, S; Hynes, S O; Mitchell, D M; Pang, B; Logan, G E; McCavigan, A M; O’Rourke, D; McArt, D G; McDade, S S; Mills, I G; Prise, K M; Knight, L A; Steele, C J; Medlow, P W; Berge, V; Katz, B; Loblaw, D A; Harkin, D P; James, J A; 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 29 (1), 215-222
dc.identifier.issn0923-7534,1569-8041
dc.identifier.urihttp://hdl.handle.net/10379/12069
dc.description.abstractBackground: 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 metastasisfree 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 [HR = 3.21 (1.35-7.67); P = 0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR = 2.71 (1.11-6.63); P = 0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR = 3.23 (1.22-8.59); P = 0.019] whilst CAPRA itself was not significant [HR = 1.88, (0.52-6.77); P = 0.332]. 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.
dc.publisherOxford University Press (OUP)
dc.relation.ispartofAnnals of Oncology
dc.subjectprostate cancer
dc.subjectrisk stratification
dc.subjectradiation therapy
dc.subjectprognostic
dc.subjectmetastatic
dc.subjectbiomarker
dc.subjectparaffin-embedded tissue
dc.subjectandrogen suppression
dc.subjectdose-escalation
dc.subjecttrial
dc.subjectrecommendations
dc.subjectintermediate
dc.subjectradiotherapy
dc.subjectmen
dc.titleValidation of a metastatic assay using biopsies to improve risk stratification in patients with prostate cancer treated with radical radiation therapy
dc.typeArticle
dc.identifier.doi10.1093/annonc/mdx637
dc.local.publishedsourcehttps://academic.oup.com/annonc/article-pdf/29/1/215/23561017/mdx637.pdf
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