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The Canadian Journal of Urology Aug 2020Prostate cancer is a common malignancy with highly variable clinical presentation and outcomes. Diagnosis and management remain a challenge and at times become highly... (Review)
Review
INTRODUCTION
Prostate cancer is a common malignancy with highly variable clinical presentation and outcomes. Diagnosis and management remain a challenge and at times become highly controversial. Novel biomarker assays have shown promise as an adjunctive tool to aid in patient shared decision-making, risk stratification, and disease management. This presentation at the 2020 Jefferson Urology Symposium provided a review of current commonly used biomarkers for prostate cancer.
MATERIALS AND METHODS
We reviewed the current literature on the use of biomarkers in the diagnosis and treatment decisions in localized prostate cancer.
RESULTS
Biomarker assays were reviewed and presented according to clinical application of each test. In the consideration of initial prostate biopsy the blood tests for PHI, and 4K Score, and urine tests PCA3, Select MDx and ExoDx are available. In the consideration of treatment versus active surveillance in the biopsy positive setting OncotypeDx, Prolaris and Decipher are available. In patients with an initial negative biopsy, 4K score, PCA3, ExoDx and the tissue biopsy based Confirm MDx assay can help guide the decision to perform repeat biopsy. In the consideration for adjuvant radiation following radical prostatectomy the most extensive literature available supports the use of Prolaris or Decipher tissue assays.
CONCLUSIONS
With the significant burden of men being diagnosed with prostate cancer, it is desirable to appropriately risk stratify patients to avoid unnecessary biopsies and over-treatment in low risk patients and guide appropriate treatment strategies in high risk patients. Selected biomarkers presented are useful adjunctive precision medicine tools to aid in shared decision making and to direct treatment decisions.
Topics: Biomarkers, Tumor; Humans; Male; Prostatic Neoplasms
PubMed: 32875999
DOI: No ID Found -
Current Opinion in Oncology May 2019This overview examines the rationale for dietary interventions for prostate cancer by summarizing the current evidence base and biological mechanisms for the involvement... (Review)
Review
PURPOSE OF REVIEW
This overview examines the rationale for dietary interventions for prostate cancer by summarizing the current evidence base and biological mechanisms for the involvement of diet in disease incidence and progression.
RECENT FINDINGS
Recent data have further solidified the association between insulin resistance and prostate cancer with the homeostatic model assessment of insulin resistance. Data also show that periprostatic adipocytes promote extracapsular extension of prostate cancer through chemokines, thereby providing a mechanistic explanation for the association observed between obesity and high-grade cancer. Regarding therapeutics, hyperinsulinemia may be the cause of resistance to phosphatidylinositol-3 kinase inhibitors in the treatment of prostate cancer, leading to new investigations combining these drugs with ketogenic diets.
SUMMARY
Given the recently available data regarding insulin resistance and adipokine influence on prostate cancer, dietary strategies targeting metabolic syndrome, diabetes, and obesity should be further explored. In macronutrient-focused therapies, low carbohydrate/ketogenic diets should be favored in such interventions because of their superior impact on weight loss and metabolic parameters and encouraging clinical data. Micronutrients, including the carotenoid lycopene which is found in highest concentrations in tomatoes, may also play a role in prostate cancer prevention and prognosis through complementary metabolic mechanisms. The interplay between genetics, diet, and prostate cancer is an area of emerging focus that might help optimize therapeutic dietary response in the future through personalization.
Topics: Body Mass Index; Diet; Disease Progression; Humans; Male; Metabolic Syndrome; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant
PubMed: 30893147
DOI: 10.1097/CCO.0000000000000519 -
The Prostate Aug 2022Clinical genomic testing is becoming routine in prostate cancer, as biomarker-driven therapies such as poly-ADP ribose polymerase (PARP) inhibitors and anti-PD1... (Review)
Review
Clinical genomic testing is becoming routine in prostate cancer, as biomarker-driven therapies such as poly-ADP ribose polymerase (PARP) inhibitors and anti-PD1 immunotherapy are now approved for select men with castration-resistant prostate cancer harboring alterations in DNA repair genes. Challenges for precision medicine in prostate cancer include an overall low prevalence of actionable genomic alterations and a still limited understanding of the impact of tumor heterogeneity and co-occurring alterations on treatment response and outcomes across diverse patient populations. Expanded tissue-based technologies such as whole-genome sequencing, transcriptome analysis, epigenetic analysis, and single-cell RNA sequencing have not yet entered the clinical realm and could potentially improve upon our understanding of how molecular features of tumors, intratumoral heterogeneity, and the tumor microenvironment impact therapy response and resistance. Blood-based technologies including cell-free DNA, circulating tumor cells (CTCs), and extracellular vesicles (EVs) are less invasive molecular profiling resources that could also help capture intraindividual tumor heterogeneity and track dynamic changes that occur in the context of specific therapies. Furthermore, molecular imaging is an important biomarker tool within the framework of prostate cancer precision medicine with a capability to detect heterogeneity across metastases and potential therapeutic targets less invasively. Here, we review recent technological advances that may help promote the future implementation and value of precision oncology testing for patients with advanced prostate cancer.
Topics: Biomarkers; Genomics; Humans; Male; Neoplastic Cells, Circulating; Precision Medicine; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Tumor Microenvironment
PubMed: 35657153
DOI: 10.1002/pros.24354 -
European Urology Jul 2016To date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer. (Comparative Study)
Comparative Study Meta-Analysis Review
CONTEXT
To date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer.
OBJECTIVE
To conduct a meta-analysis assessing the overall and prostate cancer-specific mortality among patients treated with radical prostatectomy or radiotherapy for clinically-localized prostate cancer.
EVIDENCE ACQUISITION
We searched Medline, EMBASE, and the Cochrane Library through June 2015 without year or language restriction, supplemented with hand search, using Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Meta-analysis of Observational Studies in Epidemiology guidelines. We used multivariable adjusted hazard ratios (aHRs) to assess each endpoint. Risk of bias was assessed using the Newcastle-Ottawa scale.
EVIDENCE SYNTHESIS
Nineteen studies of low to moderate risk of bias were selected and up to 118 830 patients were pooled. Inclusion criteria and follow-up length varied between studies. Most studies assessed patients treated with external beam radiotherapy, although some included those treated with brachytherapy separately or with the external beam radiation therapy group. The risk of overall (10 studies, aHR 1.63, 95% confidence interval 1.54-1.73, p<0.00001; I(2)=0%) and prostate cancer-specific (15 studies, aHR 2.08, 95% confidence interval 1.76-2.47, p < 0.00001; I(2)=48%) mortality were higher for patients treated with radiotherapy compared with those treated with surgery. Subgroup analyses by risk group, radiation regimen, time period, and follow-up length did not alter the direction of results.
CONCLUSIONS
Radiotherapy for prostate cancer is associated with an increased risk of overall and prostate cancer-specific mortality compared with surgery based on observational data with low to moderate risk of bias. These data, combined with the forthcoming randomized data, may aid clinical decision making.
PATIENT SUMMARY
We reviewed available studies assessing mortality after prostate cancer treatment with surgery or radiotherapy. While the studies used have a potential for bias due to their observational design, we demonstrated consistently higher mortality for patients treated with radiotherapy rather than surgery.
Topics: Brachytherapy; Humans; Male; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Intensity-Modulated; Survival Rate
PubMed: 26700655
DOI: 10.1016/j.eururo.2015.11.010 -
Methods in Molecular Biology (Clifton,... 2018Prostate cancer is the most common malignancy diagnosed in men in the western world. The development of distant metastases and therapy resistance are major clinical...
Prostate cancer is the most common malignancy diagnosed in men in the western world. The development of distant metastases and therapy resistance are major clinical problems in the management of prostate cancer patients. In order for prostate cancer to metastasize to distant sites in the human body, prostate cancer cells have to migrate and invade neighboring tissue. Cancer cells can acquire a migratory and invasive phenotype in several ways, including single cell and collective migration. As a requisite for migration, epithelial prostate cancer cells often need to acquire a motile, mesenchymal-like phenotype. This way prostate cancer cells often lose polarity and epithelial characteristics (e.g., expression of E-cadherin homotypic adhesion receptor), and acquire mesenchymal phenotype (for example, cytoskeletal rearrangements, enhanced expression of proteolytic enzymes and other repertory of integrins). This process is referred to as epithelial-to-mesenchymal transition (EMT). Cellular invasion, one of the hallmarks of cancer, is characterized by the movement of cells through a three-dimensional matrix, resulting in remodeling of the cellular environment. Cellular invasion requires adhesion, proteolysis of the extracellular matrix, and migration of cells. Studying the migratory and invasive ability of cells in vitro represents a useful tool to assess the aggressiveness of solid cancers, including those of the prostate.This chapter provides a comprehensive description of the Transwell migration assay, a commonly used technique to investigate the migratory behavior of prostate cancer cells in vitro. Furthermore, we will provide an overview of the adaptations to the Transwell migration protocol to study the invasive capacity of prostate cancer cells, i.e., the Transwell invasion assay. Finally, we will present a detailed description of the procedures required to stain the Transwell filter inserts and quantify the migration and/or invasion.
Topics: Cell Culture Techniques; Cell Line, Tumor; Cell Movement; Epithelial-Mesenchymal Transition; Humans; Male; Neoplasm Invasiveness; Prostatic Neoplasms
PubMed: 29786787
DOI: 10.1007/978-1-4939-7845-8_4 -
Journal of the National Comprehensive... May 2019Updates to the NCCN Guidelines for Prostate Cancer include further refinements in taking a family history, new recommendations for germline and somatic testing, use of...
Updates to the NCCN Guidelines for Prostate Cancer include further refinements in taking a family history, new recommendations for germline and somatic testing, use of androgen receptor blockers for nonmetastatic castration-resistant prostate cancer, advice regarding intermittent versus continuous androgen deprivation therapy, and consideration of whether to treat the primary tumor in men diagnosed with de novo metastatic prostate cancer.
Topics: Disease Management; Humans; Male; Practice Guidelines as Topic; Prostatic Neoplasms
PubMed: 31117038
DOI: 10.6004/jnccn.2019.5011 -
Journal of the National Comprehensive... May 2019The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and...
The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.
Topics: Disease Management; Disease Susceptibility; Humans; Male; Prostatic Neoplasms
PubMed: 31085757
DOI: 10.6004/jnccn.2019.0023 -
Salud Publica de Mexico Apr 2016Prostate cancer is the most frequent tumor found in men worldwide and in Mexico in particular. Age and family history are the main risk factors. The diagnosis is made by... (Review)
Review
Prostate cancer is the most frequent tumor found in men worldwide and in Mexico in particular. Age and family history are the main risk factors. The diagnosis is made by prostate biopsy in patients with abnormalities detected in their prostate-specific antigen (PSA) levels or digital rectal exam (DRE). This article reviews screening and diagnostic methods as well as treatment options for patients diagnosed with prostate cancer.
Topics: Antineoplastic Agents, Hormonal; Early Detection of Cancer; Humans; Male; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Conformal; Risk Factors
PubMed: 27557386
DOI: 10.21149/spm.v58i2.7797 -
World Journal of Urology Dec 2019To review the current understanding and recent developments regarding the concept of oligometastases in hormone-sensitive prostate cancer.
PURPOSE
To review the current understanding and recent developments regarding the concept of oligometastases in hormone-sensitive prostate cancer.
METHODS
A comprehensive literature search of electronic databases, including PubMed and Embase was conducted for the search term 'oligometastases' in combinations with 'prostate cancer', 'hormone sensitive', 'genetics', and 'molecular'. All articles relating to these search terms have been taken into account.
RESULTS
Prostate cancer remains a major cause of morbidity and mortality worldwide. The majority of these cancer-related deaths result from metastases. Currently, there is a dichotomy in prostate cancer management where it is only deemed curable if it is localized, while any signs of metastasis relegate patients to systemic therapies to delay their inevitable death. A growing body of evidence supports the notion that aggressive treatments during the stable 'oligometastatic' state can have significant clinical benefits and potentially 'reset' prostate cancer to an earlier time point in cancer progression. This concept of oligometastases has been adopted in other cancer settings such as colorectal and non-small-cell lung cancers.
CONCLUSION
Multiple clinical and molecular biological studies have been influential in the support of a stable state in metastatic cancer progression coined 'oligometastases'. As our understanding of oligometastases in hormone-sensitive prostate cancer develops, we will be able to molecularly define the oligometastatic state and develop clinically available diagnostic tests. In doing so, prostate cancer patients will experience significant clinical benefits and the burden of prostate cancer worldwide will likely be reduced.
Topics: Androgen Antagonists; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms
PubMed: 30382379
DOI: 10.1007/s00345-018-2542-x -
The New England Journal of Medicine Apr 2023
Topics: Humans; Male; Prostatectomy; Prostatic Neoplasms
PubMed: 36912567
DOI: 10.1056/NEJMe2300807