Prognostic importance of concomitant non‐regional lymph node and bone metastases in men with newly diagnosed metastatic prostate cancer

Abstract Background The aim of the study was to examine the value of quantitative and qualitative MRI and 11C acetate PET/CT parameters in predicting regional lymph node (LN) metastasis of newly diagnosed prostate cancer (PCa). Patients and methods Patients with intermediate (n = 6) and high risk (n = 47) PCa underwent 3T MRI (40 patients) and 11C acetate PET/CT (53 patients) before extended pelvic LN dissection. For each patient the visually most suspicious LN was assessed for mean apparent diffusion coefficient (ADCmean), maximal standardized uptake value (SUVmax), size and shape and the primary tumour for T stage on MRI and ADCmean and SUVmax in the index lesion. The variables were analysed in simple and multiple logistic regression analysis. Results All variables, except ADCmean and SUVmax of the primary tumor, were independent predictors of LN metastasis. In multiple logistic regression analysis the best model was ADCmean in combintion with MRI T-stage where both were independent predictors of LN metastasis, this combination had an AUC of 0.81 which was higher than the AUC of 0.65 for LN ADCmean alone and the AUC of 0.69 for MRI T-stage alone. Conclusions Several quantitative and qualitative imaging parameters are predictive of regional LN metastasis in PCa. The combination of ADCmean in lymph nodes and T-stage on MRI was the best model in multiple logistic regression with increased predictive value compared to lymph node ADCmean and T-stage on MRI alone.

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1197: Prognostic Value of Hemoglobin Change after Initiation of Androgen Deprivations Therapy for Newly Diagnosed Metastatic Prostate Cancer: A Multivariate Analysis of Swog 8894

The Journal of Urology ◽

10.1016/s0022-5347(18)33422-0 ◽

2006 ◽

Vol 175 (4S) ◽

pp. 385-386

Author(s):

Tomasz M. Beer ◽

Bryan H. Goldman ◽

Catherine M. Tangen ◽

Lisa B. Bland ◽

Maha Hussain ◽

...

Keyword(s):

Prostate Cancer ◽

Multivariate Analysis ◽

Prognostic Value ◽

Metastatic Prostate Cancer ◽

Newly Diagnosed

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Cost-effectiveness analysis of innovative therapy for patients with newly diagnosed hormone-sensitive metastatic prostate cancer

Clinical Genitourinary Cancer ◽

10.1016/j.clgc.2021.03.022 ◽

2021 ◽

Author(s):

Rémi Pelloux-Prayer ◽

Philomène Schiele ◽

Stéphane Oudard ◽

Gwenaëlle Gravis ◽

François Kleinclauss ◽

...

Keyword(s):

Prostate Cancer ◽

Cost Effectiveness ◽

Metastatic Prostate Cancer ◽

Cost Effectiveness Analysis ◽

Newly Diagnosed ◽

Innovative Therapy ◽

Effectiveness Analysis ◽

Hormone Sensitive

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Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2020-042953 ◽

2021 ◽

Vol 11 (2) ◽

pp. e042953

Author(s):

Martin John Connor ◽

Taimur Tariq Shah ◽

Katarzyna Smigielska ◽

Emily Day ◽

Johanna Sukumar ◽

...

Keyword(s):

Prostate Cancer ◽

Lymph Node ◽

Androgen Receptor ◽

Randomised Controlled Trial ◽

Phase Ii ◽

Metastatic Prostate Cancer ◽

Controlled Trial ◽

Pelvic Lymph Node ◽

Study Results ◽

Randomised Controlled

IntroductionSurvival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone.MethodsA phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024.Ethics and disseminationApproved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03763253; ISCRTN58401737

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A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer

Clinical Epigenetics ◽

10.1186/s13148-021-01119-0 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Erik Bovinder Ylitalo ◽

Elin Thysell ◽

Mattias Landfors ◽

Maria Brattsand ◽

Emma Jernberg ◽

...

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Androgen Receptor ◽

Bone Metastases ◽

Metastatic Prostate Cancer ◽

Tumor Biology ◽

Receptor Activity ◽

Mrna Levels ◽

Androgen Receptor Activity ◽

Patient Prognosis

Abstract Background Patients with metastatic prostate cancer (PC) are treated with androgen deprivation therapy (ADT) that initially reduces metastasis growth, but after some time lethal castration-resistant PC (CRPC) develops. A better understanding of the tumor biology in bone metastases is needed to guide further treatment developments. Subgroups of PC bone metastases based on transcriptome profiling have been previously identified by our research team, and specifically, heterogeneities related to androgen receptor (AR) activity have been described. Epigenetic alterations during PC progression remain elusive and this study aims to explore promoter gene methylation signatures in relation to gene expression and tumor AR activity. Materials and methods Genome-wide promoter-associated CpG methylation signatures of a total of 94 tumor samples, including paired non-malignant and malignant primary tumor areas originating from radical prostatectomy samples (n = 12), and bone metastasis samples of separate patients with hormone-naive (n = 14), short-term castrated (n = 4) or CRPC (n = 52) disease were analyzed using the Infinium Methylation EPIC arrays, along with gene expression analysis by Illumina Bead Chip arrays (n = 90). AR activity was defined from expression levels of genes associated with canonical AR activity. Results Integrated epigenome and transcriptome analysis identified pronounced hypermethylation in malignant compared to non-malignant areas of localized prostate tumors. Metastases showed an overall hypomethylation in relation to primary PC, including CpGs in the AR promoter accompanied with induction of AR mRNA levels. We identified a Methylation Classifier for Androgen receptor activity (MCA) signature, which separated metastases into two clusters (MCA positive/negative) related to tumor characteristics and patient prognosis. The MCA positive metastases showed low methylation levels of genes associated with canonical AR signaling and patients had a more favorable prognosis after ADT. In contrast, MCA negative patients had low AR activity associated with hypermethylation of AR-associated genes, and a worse prognosis after ADT. Conclusions A promoter methylation signature classifies PC bone metastases into two groups and predicts tumor AR activity and patient prognosis after ADT. The explanation for the methylation diversities observed during PC progression and their biological and clinical relevance need further exploration.

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