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Advances in Genetics 2021Prostate cancer heritability is attributed to a combination of rare, moderate to highly penetrant genetic variants as well as commonly occurring variants conferring...
Prostate cancer heritability is attributed to a combination of rare, moderate to highly penetrant genetic variants as well as commonly occurring variants conferring modest risks [single nucleotide polymorphisms (SNPs)]. Some of the former type of variants (e.g., BRCA2 mutations) predispose particularly to aggressive prostate cancer and confer poorer prognoses compared to men who do not carry mutations. Molecularly targeted treatments such as PARP inhibitors have improved outcomes in men carrying somatic and/or germline DNA repair gene mutations. Ongoing clinical trials are exploring other molecular targeted approaches based on prostate cancer somatic alterations. Genome wide association studies have identified >250 loci that associate with prostate cancer risk. Multi-ancestry analyses have identified shared as well as population specific risk SNPs. Prostate cancer risk SNPs can be used to estimate a polygenic risk score (PRS) to determine an individual's genetic risk of prostate cancer. The odds ratio of prostate cancer development in men whose PRS lies in the top 1% of the risk profile ranges from 9 to 11. Ongoing studies are investigating the utility of a prostate cancer PRS to target population screening to those at highest risk. With the advent of personalized medicine and development of DNA sequencing technologies, access to clinical genetic testing is increasing, and oncology guidelines from bodies such as NCCN and ESMO have been updated to provide criteria for germline testing of "at risk" healthy men as well as those with prostate cancer. Both germline and somatic prostate cancer research have significantly evolved in the past decade and will lead to further development of precision medicine approaches to prostate cancer treatment as well as potentially developing precision population screening models.
Topics: Early Detection of Cancer; Genetic Predisposition to Disease; Genetic Testing; Genome-Wide Association Study; Germ-Line Mutation; Humans; Male; Prostatic Neoplasms
PubMed: 34844712
DOI: 10.1016/bs.adgen.2021.08.006 -
Current Problems in Cancer Aug 2023Nearly 15% of individuals with localized prostate cancer are identified as high risk for recurrence and progression of the disease, which is why the correct staging is... (Review)
Review
Nearly 15% of individuals with localized prostate cancer are identified as high risk for recurrence and progression of the disease, which is why the correct staging is vital for the definition of correct treatment-also developing novel therapeutic strategies to find a balance between getting better outcomes without sacrificing the quality of life (QoL). In this narrative review, we introduced the current standards of staging and primary treatment of high-risk localized prostate cancer (PCa), based on international guidelines and arguments in the debate, under the light of the most recent literature. It brings essential tools such as PSMA PET/CT and different nomograms (Briganti. MSKCC, Gandaglia) for accurate staging and selecting wisely the definitive therapy. Even though there is a broad discussion over the best local treatment in curative-intent treatment, it looks more important to define which patient profile would adapt correctly to every different treatment, highlighting the benefits and superior outcomes with multimodal treatment.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Quality of Life; Prostatic Neoplasms; Nomograms; Neoplasm Staging
PubMed: 37418998
DOI: 10.1016/j.currproblcancer.2023.100993 -
Cold Spring Harbor Perspectives in... Oct 2018Cancer cells hijack metabolic pathways to support bioenergetics and biosynthetic requirements for their uncontrolled growth. Thus, cancer can be considered as a... (Review)
Review
Cancer cells hijack metabolic pathways to support bioenergetics and biosynthetic requirements for their uncontrolled growth. Thus, cancer can be considered as a metabolic disease. In this review, we discuss the main metabolic features of prostate cancer with a particular focus on the link between oncogene-directed cancer metabolic regulation, metabolism rewiring, and epigenetic regulation. The potential of using metabolic profiling as a means to predict disease behavior and to identify novel therapeutic targets and new diagnostic markers will be addressed as well as the current challenges in metabolomics analyses. Finally, diagnostic and prognostic metabolic imaging approaches, including positron emission tomography, mass spectrometry, nuclear magnetic resonance, and their translational applications, will be discussed. Here, we emphasize how targeting metabolic vulnerabilities in prostate cancer may pave the way for novel personalized diagnostic and therapeutic interventions.
Topics: Humans; Male; Prostatic Neoplasms
PubMed: 29229664
DOI: 10.1101/cshperspect.a030569 -
The Oncologist Jul 2021Prostate cancer remains the leading diagnosed cancer and the second leading cause of death among American men. Despite improvements in screening modalities, diagnostics,...
Prostate cancer remains the leading diagnosed cancer and the second leading cause of death among American men. Despite improvements in screening modalities, diagnostics, and treatment, disparities exist among Black men in this country. The primary objective of this systematic review is to describe the reported disparities in screening, diagnostics, and treatments as well as efforts to alleviate these disparities through community and educational outreach efforts. Critical review took place of retrospective, prospective, and socially descriptive data of English language publications in the PubMed database. Despite more advanced presentation, lower rates of screening and diagnostic procedures, and low rates of trial inclusion, subanalyses have shown that various modalities of therapy are quite effective in Black populations. Moreover, patients treated on prospective clinical trials and within equal-access care environments have shown similar outcomes regardless of race. Additional prospective studies and enhanced participation in screening, diagnostic and genetic testing, clinical trials, and community-based educational endeavors are important to ensure equitable progress in prostate cancer for all patients. IMPLICATIONS FOR PRACTICE: Notable progress has been made with therapeutic advances for prostate cancer, but racial disparities continue to exist. Differing rates in screening and utility in diagnostic procedures play a role in these disparities. Black patients often present with more advanced disease, higher prostate-specific antigen, and other adverse factors, but outcomes can be attenuated in trials or in equal-access care environments. Recent data have shown that multiple modalities of therapy are quite effective in Black populations. Novel and bold hypotheses to increase inclusion in clinical trial, enhance decentralized trial efforts, and enact successful models of patient navigation and community partnership are vital to ensure continued progress in prostate cancer disparities.
Topics: Black or African American; Early Detection of Cancer; Humans; Male; Prospective Studies; Prostatic Neoplasms; Retrospective Studies; United States
PubMed: 33683758
DOI: 10.1002/onco.13749 -
Archivos Espanoles de Urologia Mar 2022Prostate cancer is themost prevalent and deadliest neoplasm in men, with adiverse clinical presentantion and oncological outcomes.The diagnosis and treatment remains a... (Review)
Review
INTRODUCTION
Prostate cancer is themost prevalent and deadliest neoplasm in men, with adiverse clinical presentantion and oncological outcomes.The diagnosis and treatment remains a challenge.New essays about biomarkers show their potential asa tool that may influence in clinical decision making,risk stratification and management of the disease.
METHODS
we performed a literature review abouttissue biomarkers in the diagnosis and treatment ofprostate cancer.
RESULTS
Within the last years, a wide number ofdiagnostic and prognostic tests in tissue have been developed(ConfirmMDx, Promark, Oncoytype DX, Decipher),creating an opportunity to improve the diagnosis,prognosis and treatment of prostate cancer.
CONCLUSIONS
Since prostate cancer is the mostprevalent neoplasm in men, it is mandatory to stratifypatients correctly to prevent unnecessary biopsiesand overtreatment in low risk patients, as well as designthe best strategy in those with high risk disease.Tissue biomarkers may become a useful tool in precisionmedicine to guide decision making.
Topics: Biomarkers, Tumor; Clinical Decision-Making; Humans; Male; Prognosis; Prostatic Neoplasms
PubMed: 35332888
DOI: No ID Found -
Urology Dec 2017To critically analyze the available evidence regarding the incidence, etiopathogenesis, and management of prostate cancer (CaP) in transgender women. In addition, this... (Review)
Review
OBJECTIVE
To critically analyze the available evidence regarding the incidence, etiopathogenesis, and management of prostate cancer (CaP) in transgender women. In addition, this article aims to present a recent case report of a transgender woman with a unique presentation at the author's institution.
MATERIALS AND METHODS
An electronic nonsystematic literature search was performed to identify pertinent studies. PubMed search engine was queried by using the following search terms: "prostate cancer," "male to female transsexual," "transgender patient," "androgen + prostate cancer," "estrogen therapy + prostate cancer," and "health care barrier." In addition, a clinical case managed at our institution was reviewed and critically discussed.
RESULTS
Including our case, there have been only 10 documented cases of CaP in transgender women. Additionally, an emerging body of literature has questioned the role of androgens in the development of CaP and suggested that estrogen therapy may not be as protective as initially thought. Therefore, the current evidence suggests that the transgender woman should be screened for CaP the same as a nontransgender men. Barriers to care in the transgender female population include accessing resources, medical knowledge deficits, ethics of transition-related medical care, diagnosing vs pathologizing transgender patients, financial restrictions of the patient, and health system determinants.
CONCLUSION
Although rare, CaP in transgender women has been documented. Both the mechanism and the impact of receiving a bilateral orchiectomy on disease development are unclear. Future study is needed to examine these factors, and to further shape the treatment and screening regimen for these patients.
Topics: Disorders of Sex Development; Female; Humans; Incidence; Male; Prostatic Neoplasms; Transgender Persons
PubMed: 28882782
DOI: 10.1016/j.urology.2017.08.032 -
Oncotarget Sep 2014Prostate cancer co-opts a unique set of cellular pathways in its initiation and progression. The heterogeneity of prostate cancers is evident at earlier stages, and has... (Review)
Review
Prostate cancer co-opts a unique set of cellular pathways in its initiation and progression. The heterogeneity of prostate cancers is evident at earlier stages, and has led to rigorous efforts to stratify the localized prostate cancers, so that progression to advanced stages could be predicted based upon salient features of the early disease. The deregulated androgen receptor signaling is undeniably most important in the progression of the majority of prostate tumors. It is perhaps because of the primacy of the androgen receptor governed transcriptional program in prostate epithelium cells that once this program is corrupted, the consequences of the ensuing changes in activity are pleotropic and could contribute to malignancy in multiple ways. Following localized surgical and radiation therapies, 20-40% of patients will relapse and progress, and will be treated with androgen deprivation therapies. The successful development of the new agents that inhibit androgen signaling has changed the progression free survival in hormone resistant disease, but this has not changed the almost ubiquitous development of truly resistant phenotypes in advanced prostate cancer. This review summarizes the current understanding of the molecular pathways involved in localized and metastatic prostate cancer, with an emphasis on the clinical implications of the new knowledge.
Topics: Animals; Antineoplastic Agents; Humans; Male; Molecular Targeted Therapy; Prostatic Neoplasms
PubMed: 25277175
DOI: 10.18632/oncotarget.2406 -
Clinical Advances in Hematology &... Feb 2020Prostate cancer is the most frequently diagnosed cancer in men after skin cancer. Owing to the rising popularity of prostate-specific antigen screening, large numbers of... (Review)
Review
Prostate cancer is the most frequently diagnosed cancer in men after skin cancer. Owing to the rising popularity of prostate-specific antigen screening, large numbers of patients are receiving a diagnosis of prostate cancer and undergoing whole-gland treatment. Some patients with a diagnosis of low-risk, localized disease may not benefit from whole-gland treatment, however, given its known morbidity. In response to advances in prostate imaging and evidence suggesting that the prognosis in prostate cancer is related to the index lesion, many patients have begun to opt for focal therapy, which targets a lesion rather than the entire prostate. This "middle ground" of therapy, between active surveillance and whole-gland treatment, is appealing to patients because the risk for side effects is believed to be lower with focal therapy than with whole-gland treatment. This review discusses the oncologic rationale for focal therapy in localized prostate cancer, examines the major therapy modalities, and addresses future directions.
Topics: Combined Modality Therapy; Humans; Male; Prostate; Prostatic Neoplasms
PubMed: 32558805
DOI: No ID Found -
Seminars in Nuclear Medicine Jul 2019The current mainstay of treatment in metastatic prostate cancer is based on hormonal manipulations. Standard androgen deprivation therapy and novel androgen axis drugs... (Review)
Review
The current mainstay of treatment in metastatic prostate cancer is based on hormonal manipulations. Standard androgen deprivation therapy and novel androgen axis drugs are commonly well tolerable and can stabilize metastatic hormone-sensitive prostate cancers for years. However, metastatic castration-resistant prostate cancer is still challenging to treat. Except taxanes, prostate cancer presents intrinsic resistance against conventional chemotherapies. The typically elderly patient population excludes more aggressive treatment regimens. First clinical trials evaluating immunotherapy or tyrosine-kinase-inhibitors against prostate cancer failed. In contrast, prostate cancer can be radiosensitive and external beam radiotherapy is effective in localized prostate cancer, thus providing a good rationale for the use of systemic radiopharmaceuticals in the metastatic setting. Beta-particle emitting "bone-seekers" have a long history and are effective as analgesics but do not improve survival because they are limited by red-marrow dose. Alpha emitting Radium can be used in a dose that prolongs survival but is restricted to bone-confined patients. Currently radiolabeled high-affinity ligands to the prostate-specific membrane antigen are in clinical evaluation. While radioimmunotherapy approaches were limited by the long circulation time and slow tumor-accumulation of antibodies, low molecular weight PSMA-specific ligands offer an approx. ten-fold improved tumor to red-marrow ratio in comparison to the unspecific bone-seekers. Early clinical studies demonstrate that regarding surrogate markers, such as >50% PSA reduction (60%) and radiologic response (80%), PSMA-therapy exceeds the antitumor activity of all approved or other recently tested compounds; for example, PSA-response was only observed in approx. a total of 10% of patients treated with ipilimumab, sunitinib, cabozantinib, or xofigo, respectively and in approx. 30, 40, 50% of patients treated with abiraterone, cabazitaxel, or enzalutamide. Also progression free and overall survivals of these single-arm studies appear promising when compared to historical controls. Consecutively, the first PSMA-RLT recently advanced into phase-3 (Lu-PSMA-617; VISION-trial). Future developments aim to avoid off-target radiation by ligand-optimization and to outperform the antitumor activity of beta-emitter PSMA-RLT by labeling with highly focused, high energy transferring alpha-nuclides; however the latter potentially also increasing the risk of side-effects and additional early phase studies are needed to improve treatment protocols. Academically clinical research is developing prognostic tools to improve treatment benefit by selecting the most appropriate patients in advance.
Topics: Antigens, Surface; Bone and Bones; Glutamate Carboxypeptidase II; Humans; Male; Neoplasm Metastasis; Prognosis; Prostatic Neoplasms
PubMed: 31227054
DOI: 10.1053/j.semnuclmed.2019.02.003 -
Australasian Physical & Engineering... Mar 2019Multiparametric MRI (mpMRI) is an imaging modality that combines anatomical MR imaging with one or more functional MRI sequences. It has become a versatile tool for... (Review)
Review
Multiparametric MRI (mpMRI) is an imaging modality that combines anatomical MR imaging with one or more functional MRI sequences. It has become a versatile tool for detecting and characterising prostate cancer (PCa). The traditional role of mpMRI was confined to PCa staging, but due to the advanced imaging techniques, its role has expanded to various stages in clinical practises including tumour detection, disease monitor during active surveillance and sequential imaging for patient follow-up. Meanwhile, with the growing speed of data generation and the increasing volume of imaging data, it is highly demanded to apply computerised methods to process mpMRI data and extract useful information. Hence quantitative analysis for imaging data using radiomics has become an emerging paradigm. The application of radiomics approaches in prostate cancer has not only enabled automatic localisation of the disease but also provided a non-invasive solution to assess tumour biology (e.g. aggressiveness and the presence of hypoxia). This article reviews mpMRI and its expanding role in PCa detection, staging and patient management. Following that, an overview of prostate radiomics will be provided, with a special focus on its current applications as well as its future directions.
Topics: Algorithms; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Prostatic Neoplasms
PubMed: 30762223
DOI: 10.1007/s13246-019-00730-z