Publications by authors named "Eleni Efstathiou"

Background: Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in the current Prostate Imaging-Reporting and Data System version 2.1 (PI-RADS v2.1) is considered optional, with primary scoring based on T2-weighted imaging (T2WI) and diffusion weighted imaging (DWI).

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Background: Cabazitaxel is an effective treatment in metastatic castration-resistant prostate cancer (mCRPC) patients previously exposed to docetaxel and novel hormonal treatments. Understanding the molecular biology of mCRPC disease and taking into account the several approved treatment options, biomarkers are needed to guide decision making including cabazitaxel treatment.

Methods: Cababone was a phase II translational study that attempted to identify predictors of cabazitaxel efficacy.

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In this podcast discussion, we review the landscape of androgen deprivation therapies (ADT) for the treatment of advanced prostate cancer. Prior to 2020, available ADT options to achieve chemical castration included gonadotropin-releasing hormone receptor agonists (e.g.

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Article Synopsis
  • Innovations in advanced prostate cancer have improved outcomes, but there's still a lack of high-level evidence in clinical management, prompting the 2024 Advanced Prostate Cancer Consensus Conference to survey experts for insights.
  • A panel of 120 international experts developed and voted on 183 consensus questions through a web-based survey prior to the conference, defining consensus as ≥75% agreement.
  • The voting results highlight areas of agreement and disagreement that can guide clinical decisions and future research, with a focus on individualizing treatment based on patient characteristics and encouraging participation in clinical trials.
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Background And Objective: The phase 3 MAGNITUDE trial assessed the efficacy and safety of niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in homologous recombination repair (HRR) genes. Here we report final analysis results for patient-reported outcomes (PROs) in the HRR cohort with a focus on BRCA1/2 alterations (BRCA).

Methods: Protocol-specified endpoints evaluated patient-reported symptoms, health-related quality of life (HRQoL), and tolerability (side-effect bother) using the Brief Pain Inventory-Short Form (BPI-SF), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EQ-5D-5L questionnaires.

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Article Synopsis
  • The study focuses on first-line treatments for metastatic urothelial carcinoma of the bladder, involving either platinum-based chemotherapy, PD1/L1 inhibitors, or a combination of both; real-world data was used to analyze treatment factors and overall survival.
  • Researchers analyzed 4,169 patients diagnosed between 2014 and 2018 using the National Cancer Database, determining that older patients and those with more comorbidities were more likely to receive immunotherapy.
  • Findings indicated that combination chemoimmunotherapy improved overall survival compared to chemotherapy alone, especially in patients treated at academic facilities.
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Unlabelled: Disease progression following androgen ablation was shown to be associated with upregulation of the glucocorticoid receptor (GR). Longitudinal monitoring of GR expression in circulating extracellular vesicles (EV) may reflect changes in the tumor cell and facilitates detection of acquired resistance. We utilized LNCaP, LREX cells and a patient-derived xenograft, MDA PDX 322-2-6a, for in vitro and in vivo experiments.

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For about a decade, poly [ADP ribose] polymerases (PARP) inhibitors have been used almost exclusively to treat tumours that are deficient in one of the BRCA genes. In advanced prostate cancer, which is largely driven by the activity of the androgen receptor (AR), accumulating preclinical evidence has suggested an interplay between the AR and PARP, which could be therapeutically exploited independently of defects in the tumour's DNA homologous recombination repair (HRR) machinery. This includes the regulation of HRR genes by the AR, a mutual influence between the activities of PARP and the AR, and the co-localisation of BRCA2 to the retinoblastoma gene in the human genome.

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Article Synopsis
  • The PROSPER study focused on men with advanced prostate cancer known as non-metastatic castration-resistant prostate cancer (nmCRPC), where cancer persists despite hormone treatments.
  • Participants received either enzalutamide, a drug that inhibits androgens, or a placebo alongside androgen deprivation therapy (ADT).
  • Results showed that patients who experienced a significant decline in prostate-specific antigen (PSA) levels after enzalutamide treatment lived longer and had a lower chance of cancer spreading, indicating that PSA changes can help tailor monitoring strategies for these patients.
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Importance: Despite evidence demonstrating an overall survival benefit with up-front hormone therapy in addition to established synergy between hormone therapy and radiation, the addition of metastasis-directed therapy (MDT) to hormone therapy for oligometastatic prostate cancer, to date, has not been evaluated in a randomized clinical trial.

Objective: To determine in men with oligometastatic prostate cancer whether the addition of MDT to intermittent hormone therapy improves oncologic outcomes and preserves time with eugonadal testosterone compared with intermittent hormone therapy alone.

Design, Setting, Participants: The External Beam Radiation to Eliminate Nominal Metastatic Disease (EXTEND) trial is a phase 2, basket randomized clinical trial for multiple solid tumors testing the addition of MDT to standard-of-care systemic therapy.

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Background: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence.

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Purpose: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition.

Methods: MAGNITUDE (ClinicalTrials.

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Purpose: This post hoc analysis of PROSPER evaluated the relationship between depth of PSA decline and clinical outcomes in enzalutamide-treated men with nonmetastatic castration-resistant prostate cancer.

Materials And Methods: PROSPER was an international, randomized, double-blind, placebo-controlled, phase 3 trial that demonstrated significantly improved metastasis-free survival and overall survival with androgen deprivation therapy plus enzalutamide vs placebo. A total of 905 enzalutamide-treated men were included in this post hoc analysis.

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Introduction: While there are a plethora of studies supporting novel treatment approaches in metastatic clear cell renal cell carcinoma (ccRCC), much of the data used to inform care of patients with metastatic papillary RCC (pRCC) is extrapolated from ccRCC. Several recent phase III trials have supported the use of immunotherapy (IO) and targeted therapy (TT)+IO in ccRCC, without corresponding data for pRCC. Using ccRCC as a comparison group, we sought to describe real-world trends in the utilization of systemic therapy and its impact on overall survival (OS) among patients with metastatic pRCC.

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Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management.

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What Is This Summary About?: This is a summary of a research article originally published in . The PROSPER study involved men who had a type of advanced prostate cancer called nonmetastatic castration-resistant prostate cancer (nmCRPC). In men with nmCRPC, their cancer has progressed on traditional hormone therapy but scans show that it has not spread to other parts of the body.

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The utilization of neoadjuvant immune checkpoint inhibitor therapy, specifically anti-PD-1/L1 agents, prior to radical cystectomy is an emerging paradigm in muscle-invasive bladder cancer (MIBC). vaccination represents a strategy to manipulate the tumor in order to augment the immune response toward improved local and distant cancer control. The authors describe the study rationale, design and objectives for RAD VACCINE MIBC, a single-arm, single-institution, phase II trial evaluating the efficacy and safety of combination neoadjuvant sasanlimab (humanized IgG monoclonal antibody that targets PD-1) with stereotactic body radiotherapy as an vaccine in cisplatin-ineligible patients with MIBC.

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Single-cell RNA sequencing studies have suggested that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, have so far impeded at-scale pan-cancer examination of total mRNA content. Here we present a method to quantify tumor-specific total mRNA expression (TmS) from bulk sequencing data, taking into account tumor transcript proportion, purity and ploidy, which are estimated through transcriptomic/genomic deconvolution.

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Background: Given the low incidence of urachal carcinoma of the bladder (UCB), there is limited published data from contemporary population-based cohorts. This study aimed to describe demographic, clinicopathological features, and survival outcomes of patients diagnosed with UCB.

Methods: The National Cancer Database (2004-2016) was queried for UCB patients.

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Article Synopsis
  • There have been improvements in treating advanced prostate cancer, but some areas still need more research and evidence to help doctors make the best choices.
  • In 2021, experts gathered for a conference to vote on important questions about treating advanced prostate cancer, focusing on three big topics that people often disagree on.
  • The results of their votes can give helpful guidance to doctors and patients, but each person's treatment should still be based on their specific situation.
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Patients with advanced prostate cancer (APC) may be at greater risk for severe illness, hospitalisation, or death from coronavirus disease 2019 (COVID-19) due to male gender, older age, potential immunosuppressive treatments, or comorbidities. Thus, the optimal management of APC patients during the COVID-19 pandemic is complex. In October 2021, during the Advanced Prostate Cancer Consensus Conference (APCCC) 2021, the 73 voting members of the panel members discussed and voted on 13 questions on this topic that could help clinicians make treatment choices during the pandemic.

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Bioinformatic analysis of 94 patient-derived xenografts (PDXs), cell lines, and organoids (PCOs) identifies three intrinsic transcriptional subtypes of metastatic castration-resistant prostate cancer: androgen receptor (AR) pathway + prostate cancer (PC) (ARPC), mesenchymal and stem-like PC (MSPC), and neuroendocrine PC (NEPC). A sizable proportion of castration-resistant and metastatic stage PC (M-CRPC) cases are admixtures of ARPC and MSPC. Analysis of clinical datasets and mechanistic studies indicates that MSPC arises from ARPC as a consequence of therapy-induced lineage plasticity.

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Methylthioadenosine phosphorylase, an essential enzyme for the adenine salvage pathway, is often deficient (MTAP) in tumors with 9p21 loss and hypothetically renders tumors susceptible to synthetic lethality by antifolates targeting de novo purine synthesis. Here we report our single arm phase II trial (NCT02693717) that assesses pemetrexed in MTAP urothelial carcinoma (UC) with the primary endpoint of overall response rate (ORR). Three of 7 enrolled MTAP patients show response to pemetrexed (ORR 43%).

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Introduction: The treatment landscape in invasive primary carcinoma of the urethra of urothelial histology closely aligns that of locally advanced urothelial carcinoma of the bladder. The survival benefit of perioperative chemotherapy for men undergoing radical surgery for primary urethral urothelial carcinoma (UUC) has not yet been well-elucidated.

Patients And Methods: Using the National Cancer Database (NCDB), we identified men diagnosed with non-metastatic invasive UUC (T2-4 N0-2 M0) from 2004 to 2016 treated with radical extirpative surgery.

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