scholarly journals The Impact of Whole Genome Data on Therapeutic Decision-Making in Metastatic Prostate Cancer: A Retrospective Analysis

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1178 ◽  
Author(s):  
Megan Crumbaker ◽  
Eva K. F. Chan ◽  
Tingting Gong ◽  
Niall Corcoran ◽  
Weerachai Jaratlerdsiri ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Precision Medicine ◽  
Metastatic Prostate Cancer ◽  
Parp Inhibitor ◽  
Locally Advanced ◽  
Genomic Data ◽  
Whole Genome ◽  
Genomic Alterations ◽  
Therapeutic Decision Making ◽  
The Impact

Background: While critical insights have been gained from evaluating the genomic landscape of metastatic prostate cancer, utilizing this information to inform personalized treatment is in its infancy. We performed a retrospective pilot study to assess the current impact of precision medicine for locally advanced and metastatic prostate adenocarcinoma and evaluate how genomic data could be harnessed to individualize treatment. Methods: Deep whole genome-sequencing was performed on 16 tumour-blood pairs from 13 prostate cancer patients; whole genome optical mapping was performed in a subset of 9 patients to further identify large structural variants. Tumour samples were derived from prostate, lymph nodes, bone and brain. Results: Most samples had acquired genomic alterations in multiple therapeutically relevant pathways, including DNA damage response (11/13 cases), PI3K (7/13), MAPK (10/13) and Wnt (9/13). Five patients had somatic copy number losses in genes that may indicate sensitivity to immunotherapy (LRP1B, CDK12, MLH1) and one patient had germline and somatic BRCA2 alterations. Conclusions: Most cases, whether primary or metastatic, harboured therapeutically relevant alterations, including those associated with PARP inhibitor sensitivity, immunotherapy sensitivity and resistance to androgen pathway targeting agents. The observed intra-patient heterogeneity and presence of genomic alterations in multiple growth pathways in individual cases suggests that a precision medicine model in prostate cancer needs to simultaneously incorporate multiple pathway-targeting agents. Our whole genome approach allowed for structural variant assessment in addition to the ability to rapidly reassess an individual’s molecular landscape as knowledge of relevant biomarkers evolve. This retrospective oncological assessment highlights the genomic complexity of prostate cancer and the potential impact of assessing genomic data for an individual at any stage of the disease.

Precision Medicine Approach in Prostate Cancer

2020 ◽  
Vol 26 (31) ◽  
pp. 3783-3798
Author(s):  
Majid Assadi ◽  
Narges Jokar ◽  
Mojtaba Ghasemi ◽  
Iraj Nabipour ◽  
Ali Gholamrezanezhad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Precision Medicine ◽  
Metabolic Pathways ◽  
Locally Advanced ◽  
Omics Data ◽  
Prostate Cancers ◽  
New Treatments ◽  
Treatment Procedures ◽  
The Impact

Prostate cancer is the most prevalent type of cancer and the second cause of death in men worldwide. Various diagnostic and treatment procedures are available for this type of malignancy, but High-grade or locally advanced prostate cancers showed the potential to develop to lethal phase that can be causing dead. Therefore, new approaches are needed to prolong patients’ survival and to improve their quality of life. Precision medicine is a novel emerging field that plays an essential role in identifying new sub-classifications of diseases and in providing guidance in treatment that is based on individual multi-omics data. Multi-omics approaches include the use of genomics, transcriptomics, proteomics, metabolomics, epigenomics and phenomics data to unravel the complexity of a disease-associated biological network, to predict prognostic biomarkers, and to identify new targeted drugs for individual cancer patients. We review the impact of multi-omics data in the framework of systems biology in the era of precision medicine, emphasising the combination of molecular imaging modalities with highthroughput techniques and the new treatments that target metabolic pathways involved in prostate cancer.

scholarly journals Depression Negatively Impacts Survival of Patients with Metastatic Prostate Cancer

2018 ◽  
Vol 15 (10) ◽  
pp. 2148 ◽  
Author(s):  
Po-Hung Lin ◽  
Jui-Ming Liu ◽  
Ren-Jun Hsu ◽  
Heng-Chang Chuang ◽  
Su-Wei Chang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mortality Risk ◽  
Metastatic Prostate Cancer ◽  
Locally Advanced ◽  
P Value ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Depressed Group ◽  
Prevalence Of Depression ◽  
The Impact

The prevalence of depression in patients with cancer is high, especially for patients with advanced cancer. In this study, we evaluated the prevalence of depression in prostate cancer patients in Taiwan and the association between depression and mortality in prostate cancer. This study included 1101 newly diagnosed patients with prostate cancer. We tracked the medical information of these patients from diagnosis until the end of 2012. Patients were divided into two groups according to presence or absence of depression diagnosis, and were further divided into three stages by initial treatments: localized or locally advanced, metastatic, and castration-resistant prostate cancer. Of 1101 participants, 267 (24.3%) had depression. By the end of the follow-up period (M = 8.30 ± 3.12 years), 77 (28.8%) patients in the depression group and 194 (23.3%) in the non-depressed group died. Depression was associated with higher mortality risk, (aHR 1.37; 95% CI [ 1.04–1.80]; p value 0.01). Patients in the metastatic prostate cancer group with depression had a significantly higher mortality risk compared to the non-depressed group, (aHR, 1.49; 95% CI [1.05–2.11]; p value 0.02). The impact of depression on mortality risk was not significant in either the localized or locally advanced or the castration-resistant prostate cancer groups. Our study showed that depression is related to an increased mortality risk for patients with prostate cancer, especially for metastatic prostate cancer. These results indicate that urologists should pay attention to the mood and psychiatric disorders of patients with prostate cancer.

scholarly journals Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paula Kappler ◽  
Michael A. Morgan ◽  
Philipp Ivanyi ◽  
Stefan J. Brunotte ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Cox Regression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Biologically Active ◽  
Free Form ◽  
Total Testosterone ◽  
The Impact

AbstractTo date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.

Impact of locally advanced or metastatic prostate cancer on the quality of life

2017 ◽  
Vol 41 (6) ◽  
pp. 368-375
Author(s):  
I. López-Calderero ◽  
L. López-Fando ◽  
E. Ríos-González ◽  
P. Maisonobe ◽  
E. Hernández-Yuste ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Locally Advanced

scholarly journals Evolving Role of Genomics in Genitourinary Neoplasms

2019 ◽  
Vol 48 (1) ◽  
pp. 68
Author(s):  
Michael E. Devitt ◽  
Robert Dreicer
Keyword(s):  
Dna Damage ◽  
Genomic Data ◽  
Treatment Decisions ◽  
Response To Therapy ◽  
Genomic Alterations ◽  
Dna Damage And Repair ◽  
Genitourinary Cancer ◽  
Genitourinary Cancers ◽  
The Impact

<p>The aim of this article is to review the current role of genomic testing in the risk, prognosis, and treatment of genitourinary malignancies. The authors selected guidelines, publications, and abstracts relevant to the current and emerging role of genomics in genitourinary cancers. The risk of developing genitourinary cancer can be stratified based on genomic data. Prostate cancer has the strongest degree of heritability, with <em>BRCA1/2 </em>and <em>HOXB13 </em>mutations playing a role in familial disease. Genomic data is on the verge of informing treatment decisions across genitourinary cancers. mCRPC has diverse genomic alterations that represent potential therapeutic targets, including alterations in the AR pathway, DNA damage and repair pathways, cell cycle pathways, PI3K pathway, and Wnt signaling. Genomic alterations in clear cell renal cell carcinoma can inform prognosis and mutations in mTOR pathways predict response to mTOR inhibitors. Urothelial carcinoma can be classified into different subtypes based on gene expression profiling, which provides prognostic information and predicts response to chemotherapy and immunotherapy. Specific mutations have been identified that predict response to therapy including <em>ERCC2 </em>mutations and cisplatin, DNA damage and repair mutations and checkpoint inhibitors, and <em>FGFR3 </em>mutations and FGFR tyrosine kinase inhibitors such as erdafitinib.</p><p><strong>Conclusion. </strong>Genitourinary malignancies have not felt the impact of genomic data as greatly as other cancer types. The majority of benefit lies in identifying patients at high risk of genitourinary cancer. Fortunately, breakthroughs are on the horizon that will result in a greater incorporation of genomic information into treatment decisions for patients with genitourinary cancer.</p>

scholarly journals microRNA expression in tumour tissue and plasma in patients with newly diagnosed metastatic prostate cancer

Tumor Biology ◽  
2018 ◽  
Vol 40 (5) ◽  
pp. 101042831877586 ◽  
Author(s):  
Ahmed Hussein Zedan ◽  
Torben Frøstrup Hansen ◽  
Jannie Assenholt ◽  
Mindaugas Pleckaitis ◽  
Jonna Skov Madsen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasma Level ◽  
Advanced Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Locally Advanced ◽  
Tumour Tissue ◽  
Newly Diagnosed ◽  
Locally Advanced Prostate Cancer ◽  
Mirna 93 ◽  
Benign Prostate

Prostate cancer is the most common cancer among men in the western world. Clinical practice is continuously challenged by the pitfalls of the available diagnostic tools. microRNAs may represent promising biomarkers in many types of human cancers, including prostate cancer. The aim of this study was to investigate microRNA expression in tumour tissue and matched plasma in a cohort of patients with primary metastatic prostate cancer. The relative expression of 12 microRNAs was assessed in diagnostic needle biopsies from the prostate and matched plasma samples in two prospective cohorts (screening cohorts) comprising 21 patients with metastatic prostate cancer and 25 control patients. An independent validation cohort of plasma samples was collected prospectively from 149 newly diagnosed patients with local/locally advanced prostate cancer. Analyses were performed using real-time polymerase chain reaction. miRNA-93 showed a significant negative correlation between expression in tumour tissue and plasma in patients with metastatic prostate cancer. Furthermore, the plasma level of miRNA-93 significantly decreased after treatment in patients with local/locally advanced prostate cancer compared to baseline plasma level. The expression of six microRNAs (let-7b, miRNA-34a, -125b, -143, -145 and -221) was downregulated, and three microRNAs (miRNA-21, -25 and miRNA-93) were upregulated in tumour tissue compared to benign prostate tissue. In plasma, six microRNAs were upregulated (miRNA-21, -125b, -126, -141, -143 and -375), while let-7b was downregulated in patients with metastatic prostate cancer compared to the control cohort. In the metastatic prostate cancer cohort, the expression of four microRNAs (miRNA-125b, -126, -143 and -221), and miRNA-141 in tissue was associated with Gleason score and prostate-specific antigen, respectively. The expression of miRNA-93 in tumour tissue was correlated with matched plasma levels and showed a significant decrease in plasma level after intervention in local prostate cancer. Differential expression between tumour and benign prostate was detected for several microRNAs in both tissue and plasma.

Associations of pre-existing cardiovascular disease (CVD) with treatment patterns and survival outcomes in patients with metastatic prostate cancer: A real-world, population-based study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17056-e17056
Author(s):  
Atul Batra ◽  
Shiying Kong ◽  
Winson Y. Cheung
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Population Based ◽  
Treatment Patterns ◽  
Survival Outcomes ◽  
Administrative Claims ◽  
World Population ◽  
Cancer Treatments ◽  
Lower Likelihood ◽  
The Impact

e17056 Background: Prior cardio-oncology research has focused on examining the future risk of CVD as a result of cancer treatments. The impact of pre-existing CVD on cancer treatments is less clear. This study aimed to identify the associations of baseline CVD on treatment patterns and survival outcomes in metastatic prostate cancer where older age and exposure to androgen deprivation therapy can potentiate cardiac risks. Methods: We identified all patients diagnosed with metastatic prostate cancer in a large Canadian province from 2004 to 2017 using the population-based cancer registry. Administrative claims were linked to ascertain any diagnoses of pre-existing CVD, defined as any of arrythmias [AR], cerebrovascular accidents [CVAs], myocardial infarctions [MIs], or congestive heart failure [CHF] that preceded the diagnosis of metastatic prostate cancer. Logistic and Cox regression models were constructed to determine the associations of baseline CVD with receipt of cancer treatments (such as radiation, or systemic therapy) and overall survival (OS). Results: A total of 3,257 patients were included. The median age was 66 years (interquartile range, 46-95 years). At diagnosis of advanced prostate cancer, 993 (30.5%) had pre-existing CVD: 10.0% AR, 4.3% CVAs, 3.0% MIs, 2.8% CHF and 10.4% multiple CVDs. The Charlson comorbidity index (CCI) was 0, 1 and >1 in 53.4%, 27.3% and 19.3%, respectively. Overall, 2078 (63.8%) patients received chemotherapy, while 747 (22.9%) received radiotherapy. After adjusting for age and CCI, pre-existing CVD was associated with a lower likelihood of chemotherapy (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.61-0.75; P=0.001) and radiotherapy (OR, 0.87; 95% CI, 0.85-0.91; P<0.001). Likewise, CVD was associated with worse OS, after adjusting for measured confounding variables (see table). Conclusions: One-third of patients with metastatic prostate cancer had pre-existing CVD, which was associated with a lower likelihood of chemotherapy and worse OS. In the context of an aging general population, early cardio-oncology consultations to optimize CVD management may lead to safer and broader uptake of appropriate prostate cancer treatments.[Table: see text]

scholarly journals Accelerating precision medicine in metastatic prostate cancer

Nature Cancer ◽  
2020 ◽  
Vol 1 (11) ◽  
pp. 1041-1053
Author(s):  
Joaquin Mateo ◽  
Rana McKay ◽  
Wassim Abida ◽  
Rahul Aggarwal ◽  
Joshi Alumkal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Precision Medicine ◽  
Metastatic Prostate Cancer

scholarly journals Estudo Unicêntrico Prospetivo de Avaliação Sistemática da Dor em Doentes Portugueses com Cancro da Próstata Metastizado

2017 ◽  
Vol 30 (11) ◽  
pp. 796
Author(s):  
Maria Inês Sequeira ◽  
Nuno Sousa ◽  
Maria Fragoso ◽  
Alexandra Silva ◽  
Filipa Pereira ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pain Intensity ◽  
Metastatic Prostate Cancer ◽  
Short Form ◽  
Brief Pain Inventory ◽  
Life Assessment ◽  
Medical Interventions ◽  
Reduction Of Pain ◽  
Prevalence Of Pain ◽  
The Impact

Introduction: Pain is one of the most common symptoms reported by cancer patients and is associated with decreased quality of life. Assessment of pain with standardized questionnaires reduces variability in its interpretation and may increase effectiveness of medical interventions. Prostate cancer is the most frequent male neoplasm in Portugal. We designed this study to evaluate the impact of a standardized pain questionnaire on pain management in patients with metastatic prostate cancer.Material and Methods: Single centre prospective observational study of patients with metastatic prostate cancer. The study was designed to evaluate the benefit of systematically evaluating pain with Brief Pain Inventory-Short Form prior to a scheduled medical oncology consult. Patients reporting pain were reassessed one week later by telephone. To assess the benefit two consecutive cohorts were established based on communication of questionnaire results to the treating physician.Results: We recruited 207 patients of which 60% reported pain. Statistically significant decrease in mean pain intensity one week after the scheduled appointment was noted (3.95 vs 3.01; p < 0.001). Patients whose Brief Pain Inventory-Short Form was provided to their oncologist experienced greater reduction in pain, which was non-significant (p = 0.227). Using Brief Pain Inventory-Short Form assessment resulted in a higher probability of pain control (43.5% vs 30.9%; p = 0.193).Discussion: The prevalence of pain founded was higher than described in the literature, probably because our sample was less selected than the published in clinical trials. After the scheduled appointment, there was a statistically significant reduction in mean pain intensity, but the explicit use of this questionnaire was not associated with a statistically significant reduction of pain.Conclusion: Patients with metastatic prostate cancer have a high prevalence of pain. Evaluation and treatment by medical oncologists is associated with a reduction of mean pain intensity. The use of Brief Pain Inventory-Short Form was associated with a non-significant increased reduction of pain.

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