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International Journal of Molecular... Feb 2024Prostate cancer (PCa) represents the second most diagnosed tumor and the fifth most common cause of cancer death in men globally [...].
Prostate cancer (PCa) represents the second most diagnosed tumor and the fifth most common cause of cancer death in men globally [...].
Topics: Humans; Male; Prostatic Neoplasms
PubMed: 38396731
DOI: 10.3390/ijms25042054 -
Radiologic Clinics of North America Jan 2024Prostate cancer is the most common malignancy diagnosed in men. MR imaging-guided therapies for prostate cancer have become an increasingly common treatment alternative... (Review)
Review
Prostate cancer is the most common malignancy diagnosed in men. MR imaging-guided therapies for prostate cancer have become an increasingly common treatment alternative to traditional whole-gland therapies, such as radical prostatectomy or radiation therapy. This is especially true in men with localized, low- to intermediate-risk prostate cancer. Although long-term oncologic data remain limited, the authors describe several MR imaging-guided therapeutic options for the treatment of prostate cancer, including cryoablation, laser ablation, transrectal high-intensity focused ultrasound, and transurethral ultrasound ablation.
Topics: Male; Humans; Prostatic Neoplasms; Prostate; Magnetic Resonance Imaging; Treatment Outcome
PubMed: 37973238
DOI: 10.1016/j.rcl.2023.06.012 -
European Urology Aug 2023Few phase 3 studies have evaluated optimal systemic treatment strategies for patients with oligometastatic hormone-sensitive prostate cancer (HSPC), who may be at risk... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Few phase 3 studies have evaluated optimal systemic treatment strategies for patients with oligometastatic hormone-sensitive prostate cancer (HSPC), who may be at risk of undertreatment.
OBJECTIVE
To evaluate outcomes for patients with oligometastatic and polymetastatic HSPC treated with enzalutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT.
DESIGN, SETTING, AND PARTICIPANTS
This was a post hoc analysis of data for 927 patients with nonvisceral metastatic HSPC in the ARCHES trial (NCT02677896).
INTERVENTION
Patients were randomized 1:1 to enzalutamide (160 mg/d orally) plus ADT or placebo plus ADT with HSPC categorized as oligometastatic (1-5 metastases) or polymetastatic (≥6 metastases).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The treatment effect on radiographic progression-free survival (rPFS), overall survival (OS), and secondary efficacy endpoints was evaluated in terms of the number of metastases. Safety was assessed. Cox proportional hazards models were used to generate hazard ratios (HRs). The Brookmeyer and Crowley method was used to generate 95% confidence intervals (CIs) for Kaplan-Meier median values.
RESULTS AND LIMITATIONS
Enzalutamide plus ADT improved rPFS (HR 0.27, 95% CI 0.16-0.46; p < 0.001), OS (HR 0.59, 95% CI 0.40-0.87; p < 0.005), and secondary endpoints in patients with oligometastatic or polymetastatic disease (rPFS: HR 0.33, 95% CI 0.23-0.46; p < 0.001; OS: HR 0.55, 95% CI 0.41-0.74; p < 0.001). Safety profiles were generally similar across subgroups. Limitations include the small numbers of patients with fewer than three metastases.
CONCLUSIONS
This post hoc analysis demonstrated the utility of enzalutamide, irrespective of metastatic burden or type of oligometastatic disease, and suggests that earlier treatment intensification with systemic potent androgen receptor inhibition is advantageous.
PATIENT SUMMARY
This study considered two treatment options for metastatic hormone-sensitive prostate cancer in patients with one to five metastases or six or more metastases. Treatment with enzalutamide plus ADT improved survival and other outcomes over ADT alone, whether patients had few or many metastases.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Androgens; Disease-Free Survival; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome
PubMed: 37179240
DOI: 10.1016/j.eururo.2023.04.002 -
Journal of Nanobiotechnology Dec 2023Current diagnostic tools for prostate cancer (PCa) diagnosis and risk stratification are insufficient. The hidden onset and poor efficacy of traditional therapies... (Review)
Review
Current diagnostic tools for prostate cancer (PCa) diagnosis and risk stratification are insufficient. The hidden onset and poor efficacy of traditional therapies against metastatic PCa make this disease a heavy burden in global men's health. Prostate cancer-derived extracellular vesicles (PCDEVs) have garnered attention in recent years due to their important role in communications in tumor microenvironment. Recent advancements have demonstrated PCDEVs proteins play an important role in PCa invasion, progression, metastasis, therapeutic resistance, and immune escape. In this review, we briefly discuss the applications of sEV proteins in PCa diagnosis and prognosis in liquid biopsy, focus on the roles of the PCa-derived small EVs (sEVs) proteins in tumor microenvironment associated with cancer progression, and explore the therapeutic potential of sEV proteins applied for future metastatic PCa therapy.
Topics: Male; Humans; Prostatic Neoplasms; Prognosis; Extracellular Vesicles; Liquid Biopsy; Tumor Microenvironment
PubMed: 38093355
DOI: 10.1186/s12951-023-02219-0 -
La Clinica Terapeutica 2023In the last decade, Prostate Cancer (PCa) has emerged as the second most prevalent and serious medical condition, and is considered one of the leading factors... (Review)
Review
In the last decade, Prostate Cancer (PCa) has emerged as the second most prevalent and serious medical condition, and is considered one of the leading factors contributing to global mortality rates. Several factors (genetic as well as environmental) contribute to its development and seriousness. Since the disease is usually asymptomatic at early stages, it is typically misdiagnosed or over-diagnosed by the diagnostic procedures currently in use, leading to improper treatment. Effective biomarkers and diagnostic techniques are desperately needed in clinical settings for better management of PCa patients. Studies integrating omics sciences have shown that the accuracy and dependability of diagnostic and prognostic evaluations have increased because of the use of omics data; also, the treatment plans using omics can be facilitated by personalized medicine. The present review emphasizes innovative multi-omics methodologies, encompassing proteomics, genomics, microbiomics, metabolomics, and transcriptomics, with the aim of comprehending the molecular alterations that trigger and contribute to PCa. The review shows how early genomic and transcriptomic research has made it possible to identify PCa-related genes that are controlled by tumor-relevant signaling pathways. Proteomic and metabolomic analyses have recently been integrated, advancing our understanding of the complex mechanisms at play, the multiple levels of regulation, and how they interact. By applying the omics approach, new vulnerabilities may be discovered, and customized treatments with improved efficacy will soon be accessible.
Topics: Humans; Male; Proteomics; Precision Medicine; Genomics; Prostatic Neoplasms; Biomarkers
PubMed: 37994753
DOI: 10.7417/CT.2023.2476 -
Urologic Oncology Aug 2023Prostate cancer (CaP) is the second leading cause of cancer death and displays a broad range of clinical behavior from relatively indolent to aggressive metastatic... (Review)
Review
Prostate cancer (CaP) is the second leading cause of cancer death and displays a broad range of clinical behavior from relatively indolent to aggressive metastatic disease. The etiology of most cases of CaP is not understood completely, which makes it imperative to search for the molecular basis of CaP and markers for early diagnosis. Epigenetic modifications, including changes in DNA methylation patterns, histone modifications, miRNAs, and lncRNAs are key drivers of prostate tumorigenesis. These epigenetic defects might be due to deregulated expression of the epigenetic machinery, affecting the expression of several important genes like GSTP1, RASSF1, CDKN2, RARRES1, IGFBP3, RARB, TMPRSS2-ERG, ITGB4, AOX1, HHEX, WT1, HSPE, PLAU, FOXA1, ASC, GPX3, EZH2, LSD1, etc. In this review, we highlighted the most important epigenetic gene alterations and their variations as a diagnostic marker and target for therapeutic intervention of CaP in the future. Characterization of epigenetic changes involved in CaP is obscure and adequate validation studies are still required to corroborate the present results that would be the impending future of transforming basic research settings into clinical practice.
Topics: Male; Humans; Prostatic Neoplasms; Epigenesis, Genetic; MicroRNAs; DNA Methylation; Biomarkers; Membrane Proteins
PubMed: 37032230
DOI: 10.1016/j.urolonc.2023.03.005 -
Cancer Jul 2023Prostate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression-based subtyping model based on prostate-specific biological processes was...
BACKGROUND
Prostate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression-based subtyping model based on prostate-specific biological processes was sought.
METHODS
Unsupervised machine learning of gene expression profiles from prospectively collected primary prostate tumors (training, n = 32,000; evaluation, n = 68,547) was used to create a prostate subtyping classifier (PSC) based on basal versus luminal cell expression patterns and other gene signatures relevant to PCa biology. Subtype molecular pathways and clinical characteristics were explored in five other clinical cohorts.
RESULTS
Clustering derived four subtypes: luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), and basal neuroendocrine (BN). LP and LD tumors both had higher androgen receptor activity. LP tumors also had a higher expression of cell proliferation genes, MYC activity, and characteristics of homologous recombination deficiency. BI tumors possessed significant interferon γactivity and immune infiltration on immunohistochemistry. BN tumors were characterized by lower androgen receptor activity expression, lower immune infiltration, and enrichment with neuroendocrine expression patterns. Patients with LD tumors had less aggressive tumor characteristics and the longest time to metastasis after surgery. Only patients with BI tumors derived benefit from radiotherapy after surgery in terms of time to metastasis (hazard ratio [HR], 0.09; 95% CI, 0.01-0.71; n = 855). In a phase 3 trial that randomized patients with metastatic PCa to androgen deprivation with or without docetaxel (n = 108), only patients with LP tumors derived survival benefit from docetaxel (HR, 0.21; 95% CI, 0.09-0.51).
CONCLUSIONS
With the use of expression profiles from over 100,000 tumors, a PSC was developed that identified four subtypes with distinct biological and clinical features.
PLAIN LANGUAGE SUMMARY
Prostate cancer can behave in an indolent or aggressive manner and vary in how it responds to certain treatments. To differentiate prostate cancer on the basis of biological features, we developed a novel RNA signature by using data from over 100,000 prostate tumors-the largest data set of its kind. This signature can inform patients and physicians on tumor aggressiveness and susceptibilities to treatments to help personalize cancer management.
Topics: Humans; Male; Prostatic Neoplasms; Receptors, Androgen; Docetaxel; Androgen Antagonists; Gene Expression Profiling; Phenotype; Biomarkers, Tumor; Prognosis
PubMed: 37060201
DOI: 10.1002/cncr.34790 -
The Prostate Aug 2023Locally recurrent prostate cancer following primary external beam radiotherapy without distant metastasis is a challenging problem, with no current consensus on the... (Review)
Review
BACKGROUND
Locally recurrent prostate cancer following primary external beam radiotherapy without distant metastasis is a challenging problem, with no current consensus on the optimal management of these patients. Traditional whole-gland salvage treatments offered up to a 50% 5-year disease-free survival rate but with troubling levels of risk for significant complications. Recent progress in advanced imaging techniques has allowed a more accurate selection of patients with local-only recurrence and a selection of patients that may be suitable for newer partial-gland salvage treatments that may reduce late complications.
METHODS
This article reviews advances in patient selection and provides an overview of whole- and partial-gland salvage results from selected recent meta-analyses, multi-institutional series, and studies from centers of excellence for these treatment approaches.
RESULTS
Salvage radical prostatectomy produces 5-year relapse-free survival (RFS) rates in the 50%-60% range with severe gastrointestinal (GI) toxicity in < 2% but severe genitourinary (GU) toxicity in 15%-23% of patients. The whole-gland options of high and low dose rate brachytherapy and stereotactic body radiation therapy appear to offer similar 5-year control rates, with low severe GU and GI toxicity rates of 4%-8% and <2%, respectively. Cryotherapy and high-intensity focused ultrasound (HIFU) offer similar 5-year RFS rates but carry significant risks for severe GU and GI toxicity in the range of 10%-27% and <2%, respectively. Early results of partial-gland salvage techniques in selected patients appear promising, with 3-year RFS rates of 48%-72% and rare grade 3 toxicity.
CONCLUSION
It is important to understand the relative effectiveness and risks of the various treatment options to effectively counsel patients who face this distressing clinical situation. Whole-gland salvage options offer the possibility of long-term control but with significant risks of severe toxicity. Emerging data for the partial-gland salvage options in appropriately selected patients may offer hope of reasonable control rates with reduced severe toxicity.
Topics: Male; Humans; Neoplasm Recurrence, Local; Prostatic Neoplasms; Brachytherapy; Prostate; Prostatectomy; Salvage Therapy
PubMed: 37150849
DOI: 10.1002/pros.24551 -
The British Journal of Radiology Dec 2023SpaceOAR hydrogel, a novel biodegradable spacer, is increasingly used in managing prostate cancer patients undergoing radiation therapy to minimize rectal radiation dose... (Review)
Review
SpaceOAR hydrogel, a novel biodegradable spacer, is increasingly used in managing prostate cancer patients undergoing radiation therapy to minimize rectal radiation dose and associated complications. However, its use has raised new concerns regarding its potential complications and impact on subsequent imaging interpretation. This article provides a pictorial review of the imaging complications of using SpaceOAR hydrogel in prostate cancer patients. We present multiple examples demonstrating the types of complications that can occur, potential underlying mechanisms, and their impact on patient outcomes and imaging interpretation. This review aims to provide radiologists and oncologists with an updated understanding of these complications, guiding better patient management and interpretation of imaging studies.
Topics: Male; Humans; Hydrogels; Prostatic Neoplasms; Rectum; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated
PubMed: 37750832
DOI: 10.1259/bjr.20230717 -
BMJ (Clinical Research Ed.) Apr 2024
Topics: Male; Humans; Prostatic Neoplasms; Prostate-Specific Antigen; Early Detection of Cancer; Mass Screening
PubMed: 38604700
DOI: 10.1136/bmj.q817