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Is neoadjuvant androgen deprivation therapy beneficial in prostate cancer treated with definitive radiotherapy?

ABSTRACT: To determine whether neoadjuvant androgen deprivation therapy (NADT) improves clinical outcomes in patients with prostate cancer treated with definitive radiotherapy.We retrospectively reviewed medical records of 201 patients with prostate cancer treated with radiotherapy between January 1991 and December 2008. Of these, 156 patients with more than 3 years of follow-up were the subjects of this study. The median duration of follow-up was 91.2 months. NADT was given in 103 patients (66%) with median duration of 3.3 months (range, 1.0 to 7.7 months). Radiation dose was escalated gradually from 64 Gy to 81 Gy using intensity-modulated radiotherapy technique.Biochemical relapse-free survival (BCRFS) and overall survival (OS) of all patients were 72.6% and 90.7% at 5 years, respectively. BCRFS and OS of NADT group were 79.5% and 89.8% at 5 years and those of radiotherapy alone group were 58.8% and 92.3% at 5 years, respectively. Risk group (p = 0.010) and radiation dose ?70 Gy (p = 0.017) affected BCRFS independently. NADT was a significant prognostic factor in univariate analysis, but not in multivariate analysis (p = 0.073). Radiation dose ?70 Gy was only an independent factor for OS (p = 0.007; hazard ratio, 0.261; 95% confidence interval, 0.071-0.963).NADT prior to definitive radiotherapy did not result in significant benefit in terms of BCRFS and OS. NADT should not be performed routinely in the era of dose-escalated radiotherapy.

SUBMITTER: Eom KY

PROVIDER: S-EPMC4282999 | biostudies-other | 2014 Dec

REPOSITORIES: biostudies-other

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Is neoadjuvant androgen deprivation therapy beneficial in prostate cancer treated with definitive radiotherapy?

Eom Keun-Yong KY Ha Sung W SW Lee Eunsik E Kwak Cheol C Lee Sang Eun SE

Radiation oncology journal 20141230 4

<h4>Purpose</h4>To determine whether neoadjuvant androgen deprivation therapy (NADT) improves clinical outcomes in patients with prostate cancer treated with definitive radiotherapy.<h4>Materials and methods</h4>We retrospectively reviewed medical records of 201 patients with prostate cancer treated with radiotherapy between January 1991 and December 2008. Of these, 156 patients with more than 3 years of follow-up were the subjects of this study. The median duration of follow-up was 91.2 months. ...[more]

PMID: 25568853

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Project description:BackgroundAndrogen-deprivation therapy (ADT) is standard treatment for locally advanced or metastatic prostate cancer (PCa). Many patients develop castration resistance (castration-resistant PCa [CRPC]) after approximately 2-3 yr, with a poor prognosis. The molecular mechanisms underlying CRPC progression are unclear.ObjectiveTo undertake quantitative tumour transcriptome profiling prior to and following ADT to identify functionally important androgen-regulated pathways or genes that may be reactivated in CRPC.Design, setting, and participantsRNA sequencing (RNA-seq) was performed on tumour-rich, targeted prostatic biopsies from seven patients with locally advanced or metastatic PCa before and approximately 22 wk after ADT initiation. Differentially regulated genes were identified in treatment pairs and further investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on cell lines and immunohistochemistry on a separate CRPC patient cohort. Functional assays were used to determine the effect of pathway modulation on cell phenotypes.Outcome measurements and statistical analysisWe searched for gene expression changes affecting key cell signalling pathways that may be targeted as proof of principle in a CRPC in vitro cell line model.Results and limitationsWe identified ADT-regulated signalling pathways, including the Wnt/β-catenin signalling pathway, and observed overexpression of β-catenin in a subset of CRPC by immunohistochemistry. We validated 6 of 12 (50%) pathway members by qRT-PCR on LNCaP/LNCaP-AI cell RNAs, of which 4 (67%) demonstrated expression changes consistent with RNA-seq data. We show that the tankyrase inhibitor XAV939 (which promotes β-catenin degradation) reduced androgen-independent LNCaP-AI cell line growth compared with androgen-responsive LNCaP cells via an accumulation of cell proportions in the G0/G1 phase and reduction in the S and G2/M phases. Our biopsy protocol did not account for tumour heterogeneity, and pathway inhibition was limited to pharmacologic approaches.ConclusionsRNA-seq of paired PCa samples revealed ADT-regulated signalling pathways. Proof-of-principle inhibition of the Wnt/β-catenin signalling pathway specifically delays androgen-independent PCa cell cycle progression and proliferation and warrants further investigation as a potential target for therapy for CRPC.

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Is neoadjuvant androgen deprivation therapy beneficial in prostate cancer treated with definitive radiotherapy?

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Is neoadjuvant androgen deprivation therapy beneficial in prostate cancer treated with definitive radiotherapy?

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