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Biochimica Et Biophysica Acta. Reviews... Mar 2024Prostate cancer is unique compared to other major cancers due to the presence of multiple primary malignant foci in the majority of patients at the time of diagnosis.... (Review)
Review
Prostate cancer is unique compared to other major cancers due to the presence of multiple primary malignant foci in the majority of patients at the time of diagnosis. Each malignant focus has distinct somatic mutations and gene expression patterns, which represents a challenge for the development of prognostic tests for localized prostate cancer. Additionally, the molecular heterogeneity of advanced prostate cancer has important implications for management, particularly for patients with metastatic and locally recurrent cancer. Studies have shown that prostate cancers with mutations in DNA damage response genes are more sensitive to drugs inhibiting the poly ADP-ribose polymerase (PARP) enzyme. However, testing for such mutations should consider both spatial and temporal heterogeneity. Here, we summarize studies where multiregional genomics and transcriptomics analyses have been performed for primary prostate cancer. We further discuss the vast interfocal heterogeneity and how prognostic biomarkers and a molecular definition of the index tumor should be developed. The concept of focal treatments in prostate cancer has been evolving as a demand from patients and clinicians and is one example where there is a need for defining an index tumor. Here, biomarkers must have proven value for individual malignant foci. The potential discovery and implementation of biomarkers that are agnostic to heterogeneity are also explored as an alternative to multisample testing. Thus, deciding upon whole-organ treatment, such as radical prostatectomy, should depend on information from biomarkers which are informative for the whole organ.
Topics: Male; Humans; Prostatic Neoplasms; Prostate; Mutation; Prostatectomy; Biomarkers
PubMed: 38272101
DOI: 10.1016/j.bbcan.2024.189080 -
The Malaysian Journal of Pathology Aug 2023Prostate cancer is the second-most frequently diagnosed cancer in men worldwide. Serum prostatespecific antigen is currently used for the early detection of prostate... (Review)
Review
Prostate cancer is the second-most frequently diagnosed cancer in men worldwide. Serum prostatespecific antigen is currently used for the early detection of prostate cancer. However, new biomarkers are needed to decrease over diagnosis and over treatment of prostate cancer due to limitations of prostate-specific antigen. Recently, molecular biomarkers have shown promising results for diagnosis and prognosis of prostate cancer. Molecular biomarkers have improved the sensitivity and specificity of prostate-specific antigen and studies are ongoing to identify molecular biomarkers as a replacement for prostate-specific antigen. This review aims to give an overview of emerging molecular biomarkers for diagnosis and prognosis of prostate cancer.
Topics: Male; Humans; Prostate-Specific Antigen; Prognosis; Prostatic Neoplasms; Mutation; Neoplasms, Second Primary
PubMed: 37658525
DOI: No ID Found -
Urologic Oncology Sep 2023The management of prostate cancer has significantly evolved over the last few decades with the emergence of new diagnostic and treatment technologies, which are... (Review)
Review
The management of prostate cancer has significantly evolved over the last few decades with the emergence of new diagnostic and treatment technologies, which are typically more expensive than the previous alternatives. However, decision-making regarding which diagnostics and treatment to pursue is often influenced by perceived benefits, adverse effects, and physician recommendations, without considering the financial liability borne by patients. New technologies may exacerbate financial toxicity by replacing less costly alternatives, promoting unrealistic expectations, and expanding treatment to those who would have previously gone untreated. More judicious use of technologies with an understanding of the contexts in which they are most beneficial may help prevent avoidable financial toxicity to patients.
Topics: Male; Humans; Financial Stress; Prostatic Neoplasms
PubMed: 37173237
DOI: 10.1016/j.urolonc.2023.04.014 -
Abdominal Radiology (New York) Dec 2023Prostate cancer is the second leading cause of cancer-related deaths in men in the United States. Imaging techniques such as CT, MRI, and bone scans have traditionally... (Review)
Review
Prostate cancer is the second leading cause of cancer-related deaths in men in the United States. Imaging techniques such as CT, MRI, and bone scans have traditionally been used for diagnosis and staging. Molecular imaging modalities targeting the prostate-specific membrane antigen (PSMA) have recently gained attention due to their high affinity and accuracy. PSMA PET has been combined with other modalities such as multiparametric MRI for better diagnostic and prognostic performance. PSMA imaging has been studied at different clinical settings with a wide range of disease aggressiveness. In this review we will explore the role of PSMA PET in high-risk prostate cancer staging, biochemical recurrence, and castration-resistant prostate cancer. The primary focus of this review article is to examine the latest developments in the use of PSMA imaging and emphasize the clinical situations where its effectiveness has been demonstrated to significantly impact the treatment of prostate cancer. In addition, we will touch upon the potential future advancements of PSMA PET imaging and its evolving significance in the management of prostate cancer.
Topics: Humans; Male; Prostatic Neoplasms; Prostate-Specific Antigen; Positron Emission Tomography Computed Tomography; Choline; Neoplasm Staging; Recurrence; Molecular Targeted Therapy
PubMed: 37493837
DOI: 10.1007/s00261-023-04002-z -
The New England Journal of Medicine Oct 2023
Topics: Humans; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Retrospective Studies
PubMed: 37851879
DOI: 10.1056/NEJMe2309502 -
Current Oncology Reports Feb 2024Prostate cancer is the most frequently diagnosed non-cutaneous malignancy of men in the USA; notably, the incidence is higher among men of African, followed by European... (Review)
Review
PURPOSE OF REVIEW
Prostate cancer is the most frequently diagnosed non-cutaneous malignancy of men in the USA; notably, the incidence is higher among men of African, followed by European and Asian ancestry. Germline mutations and, in particular, mutations in DNA damage repair genes (DDRGs) have been implicated in the pathogenesis of prostate cancer. This review intends to discuss the implication of ancestry on prostate cancer, specifically in regard to lack of diversity in genomic and genetic databases and the ability of providers to properly counsel patients on the significance of cancer genetic results.
RECENT FINDINGS
Ancestral differences in prostate cancer-associated DDRG germline mutations are increasingly recognized. Guidelines for treatment by the National Comprehensive Cancer Network® (NCCN®) support germline testing in certain patients, and a myriad of genetic testing panels for DDRG mutations are now available in clinical practice. However, the consensus among providers on what genes and mutations to include in the genetic tests has evolved from experience from men of European ancestry (EA). Gaps in ancestry-informed clinical practice exist in genetic risk assessment, implementation of screening, counseling, guiding recommendations, treatment, and clinical trial enrollment. The lack of diversity in tumor genomic and genetic databases may hinder ancestry-specific disease-predisposing alterations from being discovered and targeted in prostate cancer and, therefore, impede the ability of providers to accurately counsel patients on the significance of cancer genetic test results.
Topics: Male; Humans; Germ-Line Mutation; Prostatic Neoplasms; Mutation; Genetic Testing; Genetic Predisposition to Disease
PubMed: 38265515
DOI: 10.1007/s11912-024-01493-x -
European Urology Dec 2023The European Association of Urology, together with consortium partners, has launched PRAISE-U (Prostate Cancer Awareness and Initiative for Screening in the European...
The European Association of Urology, together with consortium partners, has launched PRAISE-U (Prostate Cancer Awareness and Initiative for Screening in the European Union), a project involving 25 institutions across 12 countries that is funded under the EU4Health program. The aim is to reduce the morbidity and mortality of prostate cancer in EU member states via customized and risk-based screening programs.
Topics: Male; Humans; European Union; Prostatic Neoplasms; Early Detection of Cancer; Europe
PubMed: 37704541
DOI: 10.1016/j.eururo.2023.08.002 -
Critical Reviews in Oncology/hematology Dec 2023Despite remarkable progress in the last decade, metastatic prostate cancer (mPCa) remains incurable. The approval of PARP inhibitors (PARPis) represents a milestone in... (Review)
Review
Despite remarkable progress in the last decade, metastatic prostate cancer (mPCa) remains incurable. The approval of PARP inhibitors (PARPis) represents a milestone in this field, which definitively enters the era of precision medicine, as mPCa is often enriched for defects of homologous recombination repair genes. PARPis are now used as single agents for patients with metastatic castration-resistant PCa. Moreover, combinations of PARPis plus androgen-receptor targeted agents and immune checkpoint inhibitors, and earlier applications of PARPis in the metastatic hormone-sensitive PCa are under evaluation, representing the possible upcoming applications of these agents. Mechanisms of sensitization and resistance have been only partially elucidated. In our review, we summarize the current clinical evidence regarding PARPis in mPCa and the future directions of these targeted agents.
Topics: Humans; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Precision Medicine; Prostatic Neoplasms
PubMed: 37863403
DOI: 10.1016/j.critrevonc.2023.104157 -
Nature Reviews. Urology Jun 2024Metastatic prostate cancer remains an incurable lethal disease. Studies indicate that prostate cancer accumulates genomic changes during disease progression and displays... (Review)
Review
Metastatic prostate cancer remains an incurable lethal disease. Studies indicate that prostate cancer accumulates genomic changes during disease progression and displays the highest levels of chromosomal instability (CIN) across all types of metastatic tumours. CIN, which refers to ongoing chromosomal DNA gain or loss during mitosis, and derived aneuploidy, are known to be associated with increased tumour heterogeneity, metastasis and therapy resistance in many tumour types. Paradoxically, high CIN levels are also proposed to be detrimental to tumour cell survival, suggesting that cancer cells must develop adaptive mechanisms to ensure their survival. In the context of prostate cancer, studies indicate that CIN has a key role in disease progression and might also offer a therapeutic vulnerability that can be pharmacologically targeted. Thus, a comprehensive evaluation of the causes and consequences of CIN in prostate cancer, its contribution to aggressive advanced disease and a better understanding of the acquired CIN tolerance mechanisms can translate into new tumour classifications, biomarker development and therapeutic strategies.
Topics: Humans; Chromosomal Instability; Male; Prostatic Neoplasms; Disease Progression
PubMed: 38307951
DOI: 10.1038/s41585-023-00845-9 -
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