Surgical treatment as option in treatment of metastatic hormone-sensitive prostate cancer after prior drug treatment

2022 ◽  
pp. 41-45
Author(s):  
Sh. G. Khakimova ◽  
G. G. Khakimova ◽  
G. A. Khakimov ◽  
J. B. Sadullaev
Keyword(s):  
Prostate Cancer ◽  
Surgical Treatment ◽  
Drug Treatment ◽  
Bone Metastases ◽  
Clinical Result ◽  
Metastatic Prostate Cancer ◽  
Clinical Case ◽  
Complex Treatment ◽  
Good Clinical Result ◽  
Hormone Sensitive

Currently, there is no consensus on the place of prostatectomy in the complex treatment of patients with metastatic prostate cancer. A description of a clinical case of complex treatment and observation of a patient with prostate cancer with an unfavorable baseline prognosis and the presence of bone metastases with a good clinical result is presented.

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

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.

scholarly journals Genomic Profiles of De Novo High- and Low-Volume Metastatic Prostate Cancer: Results From a 2-Stage Feasibility and Prevalence Study in the STAMPEDE Trial

2020 ◽  
pp. 882-897 ◽  
Author(s):  
Clare Gilson ◽  
Fiona Ingleby ◽  
Duncan C. Gilbert ◽  
Marina A. Parry ◽  
Nafisah B. Atako ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromatin Remodeling ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
High Volume ◽  
Pi3k Pathway ◽  
Mismatch Repair Gene ◽  
Copy Number Loss ◽  
Hormone Sensitive ◽  
Low Volume

PURPOSE The STAMPEDE trial recruits men with newly diagnosed, high-risk, hormone-sensitive prostate cancer. To ascertain the feasibility of targeted next-generation sequencing (tNGS) and the prevalence of baseline genomic aberrations, we sequenced tumor and germline DNA from patients with metastatic prostate cancer (mPCa) starting long-term androgen-deprivation therapy (ADT). METHODS In a 2-stage approach, archival, formalin-fixed, paraffin-embedded (FFPE) prostate tumor core biopsy samples were retrospectively subjected to 2 tNGS assays. Prospective enrollment enabled validation using tNGS in tumor and germline DNA. RESULTS In stage 1, tNGS data were obtained from 185 tumors from 287 patients (65%); 98% had de novo mPCa. We observed PI3K pathway aberrations in 43%, due to PTEN copy-number loss (34%) and/or activating mutations in PIK3 genes or AKT (18%) and TP53 mutation or loss in 33%. No androgen receptor ( AR) aberrations were detected; RB1 loss was observed in < 1%. In stage 2, 93 (92%) of 101 FFPE tumors (biopsy obtained within 8 months) were successfully sequenced prospectively. The prevalence of DNA damage repair (DDR) deficiency was 14% (somatic) and 5% (germline). BRCA2 mutations and mismatch repair gene mutations were exclusive to high-volume disease. Aberrant DDR (22% v 15%), Wnt pathway (16% v 4%), and chromatin remodeling (16% v 8%) were all more common in high-volume compared with low-volume disease, but the small numbers limited statistical comparisons. CONCLUSION Prospective genomic characterization is feasible using residual diagnostic tumor samples and reveals that the genomic landscapes of de novo high-volume mPCa and advanced metastatic prostate cancer have notable similarities (PI3K pathway, DDR, Wnt, chromatin remodeling) and differences ( AR, RB1). These results will inform the design and conduct of biomarker-directed trials in men with metastatic hormone-sensitive prostate cancer.

Androgen-deprivation therapy plus docetaxel-based chemotherapy in metastatic hormone-sensitive prostate cancer. A meta-analysis of randomized clinical trials.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 188-188 ◽  
Author(s):  
Allan Ramos-Esquivel ◽  
Joao M. Baptista ◽  
Luis Corrales-Rodriguez ◽  
Ileana Gonzðlez ◽  
Melissa Juarez Villegal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Androgen Deprivation Therapy ◽  
Metastatic Prostate Cancer ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Androgen Deprivation ◽  
Cochrane Central Register ◽  
Newly Diagnosed ◽  
Hormone Sensitive

188 Background: Androgen-deprivation therapy (ADT) is the standard of treatment for patients with newly diagnosed metastatic prostatic cancer. Nevertheless, recent trials have suggested a role for chemotherapy in these patients. We performed a systematic review and meta-analysis to assess the efficacy and safety of docetaxel-based chemotherapy in combination with ADT for patients with hormone-sensitive metastatic prostate cancer. Methods: Randomized clinical trials (RCT) were identified after systematic searching of electronic databases (MEDLINE, OVID and The Cochrane Central Register of Controlled Trials), as well as ASCO conference proceedings from 2010 to 2015. We included only RCT comparing ADT versus the combination of ADT plus docetaxel-based chemotherapy in patients with newly diagnosed metastatic prostate cancer. A random-effect model was used to determine the pooled hazard ratio (HR) for the efficacy outcomes: overall survival (OS) and clinical progression-free survival (PFS), according to the inverse-variance method. Heterogeneity was measured using the Q and I2statistics. Results: Three RCT (n = 2 262), were included in our meta-analysis (E3805, GETUG-AFU 15 and the M1 subgroup from STAMPEDE Trial). Docetaxel-based chemotherapy plus ADT was associated with improved OS (HR: 0.74; 95% CI: 0.60-0.90; p = 0.003). The heterogeneity of these trials was moderate (Tau2: 0.02; I2: 51%; p = 0.13). Clinical PFS was also significantly better in patients receiving docetaxel-based chemotherapy (HR: 0.67; 95% CI 0.55-0.82; p = 0.0001), with moderate between-study heterogeneity detected (Tau2: 0.01; I2: 42%; p = 0.19). Different subset of patients in these trials can explain the aforementioned heterogeneity. Regarding adverse drug reactions grade 3 or higher, neutropenia was reported in a range from 36% in the GETUG-AFU 15 Trial to 12% in the STAMPEDE trial and febrile neutropenia was reported from 6.1% in the E3805 Trial to 12% in the STAMPEDE Trial. Conclusions: The addition of docetaxel-based chemotherapy to ADT improves OS and clinical PFS. New trials are needed to determine which patients benefit the most from this intervention.

Pathogen identification in prostate cancer biopsies using transcriptome sequencing.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16545-e16545
Author(s):  
Carisa M Shah ◽  
Rohan Bareja ◽  
Olivier Elemento
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Microbial Communities ◽  
Rna Sequencing ◽  
Metastatic Prostate Cancer ◽  
Microbial Pathogens ◽  
Sequencing Data ◽  
Streptomyces Species ◽  
Microbial Species ◽  
Tumor Biopsies

e16545 Background: Tumor biopsies may frequently be associated with microbial species due to proximity with microbial communities or due to contamination during tissue processing. We examined sequencing data from tumor biopsies to explore the tumor-associated microbiome in prostate cancer. Methods: Patients were enrolled in a prospective Precision Medicine study to evaluate genomic alterations based on freshly obtained tissue biopsies. Total RNA was prepared for RNA sequencing using the standard Illumina mRNA sample preparation protocol. Paired-end RNA-sequencing at read lengths of 50 or 51 bp was performed with the HiSeq 2000 (Illumina). A total of ~268 million paired-end reads were generated, corresponding to 27 billion bases. Kraken and FusionCatcher were used to identify the metagenome that maps to microbial species. R was used to analyze the microbial pathogens and to create a heatmap of microbial abundance. We focused our analysis on prostate cancer. Results: From 1/30/2013 to 12/16/15, 83 patients with urothelial cancers were identified, of which 32 patients with prostate cancer (n = 23 from primary tumor, n = 9 metastatic prostate cancer) were sequenced. Of the 9 metastatic samples, 5 were metastatic prostate cancer to bone, 4 were other metastases. A giant cell tumor of bone was used as a control. The metagenome was identified and mapped to the Kraken pathogen database. 43 unique pathogens characterized the microbiome associated with prostate cancer, including Streptomyces species, Acinetobacter baumannii, Enterobacteriaceae, and Corynebacterium species. The most prevalent species in prostate cancer bone metastases were also the most prevalent in primary prostate tumors. Prostate cancer bone metastases clustered separately from the primary prostate cancer samples, the other metastases, and primary bone cancer. Conclusions: We have identified a putative microbiome signature associated with prostate cancer. Prostate cancer bone metastases appear to cluster separately from prostate cancer, suggesting a non-random association with microbial communities. Ongoing work is looking to (1) validate microbial association using orthogonal analyses and (2) determine the exact origin of the signature.

Audit of febrile neutropenic (FN) episodes in men receiving docetaxel for hormone-sensitive metastatic prostate cancer (HSMPC)

2016 ◽  
Vol 28 ◽  
pp. S8
Author(s):  
S. Raby ◽  
J. Mahil ◽  
C. Hughes ◽  
J. Lyons ◽  
K. Patel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Hormone Sensitive
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