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Article ; Online: Attaining precision therapy in prostate cancer: A tall order.

Efstathiou, Eleni

European journal of cancer (Oxford, England : 1990)

2017 Volume 81, Page(s) 226–227

MeSH term(s)	Humans ; Male ; Prostatic Neoplasms ; T-Lymphocytes, Cytotoxic
Language	English
Publishing date	2017-06-16
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2017.05.011
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Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 583: Show issues

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Article ; Online: The biology behind combining poly [ADP ribose] polymerase and androgen receptor inhibition for metastatic castration-resistant prostate cancer.

Agarwal, Neeraj / Zhang, Tian / Efstathiou, Eleni / Sayegh, Nicolas / Engelsberg, Arne / Saad, Fred / Fizazi, Karim

European journal of cancer (Oxford, England : 1990)

2023 Volume 192, Page(s) 113249

Abstract: 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 ... ...

Abstract	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. Based on these findings, randomised clinical trials have been initiated to study the addition of a PARP inhibitor to AR pathway inhibitor therapy. Three of four randomised studies demonstrated a significantly increased anti-tumour activity in men with metastatic prostate cancer, irrespective of HRR gene alterations. In this review, we summarise the available preclinical evidence that provides the rationale for the combination of inhibitors for PARP and the AR and discuss how it might contribute to the efficacy observed in the clinic.
MeSH term(s)	Male ; Humans ; Poly(ADP-ribose) Polymerases ; Receptors, Androgen/genetics ; Androgens ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/genetics ; Androgen Receptor Antagonists/pharmacology ; Androgen Receptor Antagonists/therapeutic use ; Adenosine Diphosphate Ribose ; Biology ; Randomized Controlled Trials as Topic
Chemical Substances	Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; Receptors, Androgen ; Androgens ; Poly(ADP-ribose) Polymerase Inhibitors ; Androgen Receptor Antagonists ; Adenosine Diphosphate Ribose (20762-30-5)
Language	English
Publishing date	2023-07-23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2023.113249
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Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: An evaluation of apalutamide for the treatment of prostate cancer.

Boukovala, Myrto / Spetsieris, Nicholas / Efstathiou, Eleni

Expert opinion on pharmacotherapy

2020 Volume 21, Issue 13, Page(s) 1537–1546

Abstract: Introduction: Novel androgen signaling inhibitors are currently standard of care in the treatment of patients with prostate cancer. Second-generation androgen receptor antagonists have demonstrated efficacy in earlier disease settings, fulfilling an ... ...

Abstract	Introduction: Novel androgen signaling inhibitors are currently standard of care in the treatment of patients with prostate cancer. Second-generation androgen receptor antagonists have demonstrated efficacy in earlier disease settings, fulfilling an unmet need in the treatment of patients with advanced prostate cancer. Areas covered: The present article focuses on the development and establishment of apalutamide among the available treatment options for prostate cancer. A literature search was performed in Pubmed/Medline for past studies and reviews of the drug. Ongoing clinical trials were also examined in the Clinicaltrials.gov online database. Expert opinion: Apalutamide has demonstrated benefit for patients with non-metastatic castration resistant and metastatic hormone naive prostate cancer. It is an efficacious, tolerable, and convenient oral agent, thus a valuable addition in the armamentarium of prostate cancer therapeutics for both non-metastatic castrate resistant and metastatic hormone naïve prostate cancer. Ongoing trials are investigating the drug as monotherapy and in combinations in other disease settings. Results are expected to further expand the drug's indications and shape the future landscape of prostate cancer therapy.
MeSH term(s)	Androgen Receptor Antagonists/therapeutic use ; Animals ; Clinical Trials as Topic ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/metabolism ; Thiohydantoins/therapeutic use ; Treatment Outcome ; Xenograft Model Antitumor Assays
Chemical Substances	Androgen Receptor Antagonists ; Thiohydantoins ; apalutamide
Language	English
Publishing date	2020-06-16
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2020.1770726
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Zs.A 5130: Show issues

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Article ; Online: Systemic Treatment of Prostate Cancer in Elderly Patients: Current Role and Safety Considerations of Androgen-Targeting Strategies.

Boukovala, Myrto / Spetsieris, Nicholas / Efstathiou, Eleni

Drugs & aging

2019 Volume 36, Issue 8, Page(s) 701–717

Abstract: Prostate cancer commonly affects older men, with one out of five patients being diagnosed at 75 years or older. Elderly patients are more likely to have reduced performance and nutritional status, increased comorbidities, polypharmacy, and altered host- ... ...

Abstract	Prostate cancer commonly affects older men, with one out of five patients being diagnosed at 75 years or older. Elderly patients are more likely to have reduced performance and nutritional status, increased comorbidities, polypharmacy, and altered host-dependent pharmacokinetics and pharmacodynamics. Moreover, elderly patients are often underrepresented in clinical trials, mainly because of comorbidities and decline in performance status. The International Society of Geriatric Oncology recommends management of elderly patients according to fitness and personal preference, rather than chronological age. Since androgen signaling has a nodal role in prostate cancer progression, androgen-targeting agents remain the mainstay of systemic therapy for this disease. However, the potential benefit of these treatments may be compromised by toxicity, especially in elderly patients. Hence, management decisions require evidence-based consideration of both potential benefits and risks on an individualized basis. Furthermore, especially elderly patients should undergo geriatric screening and must be actively monitored during treatment to detect adverse events early and prevent complications. A personalized and vigilant approach could provide the elderly patient with the optimal benefits of existing and emerging prostate cancer treatments, while sparing them the risks of excessive toxicity and avoiding overtreatment.
MeSH term(s)	Aged ; Androgen Antagonists/adverse effects ; Androgen Antagonists/therapeutic use ; Comorbidity ; Drug Discovery ; Geriatric Assessment ; Health Services for the Aged ; Humans ; Male ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology
Chemical Substances	Androgen Antagonists
Language	English
Publishing date	2019-06-06
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	1075770-3
ISSN	1179-1969 ; 1170-229X
ISSN (online)	1179-1969
ISSN	1170-229X
DOI	10.1007/s40266-019-00677-6
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Zs.A 3481: Show issues

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Article: Neuroendocrine and Aggressive-Variant Prostate Cancer.

Spetsieris, Nicholas / Boukovala, Myrto / Patsakis, Georgios / Alafis, Ioannis / Efstathiou, Eleni

Cancers

2020 Volume 12, Issue 12

Abstract: In prostate cancer, neuroendocrine (NE) differentiation may rarely present de novo or more frequently arises following hormonal therapy in patients with castration-resistant prostate cancer (CRPC). Its distinct phenotype is characterized by an aggressive ...

Abstract	In prostate cancer, neuroendocrine (NE) differentiation may rarely present de novo or more frequently arises following hormonal therapy in patients with castration-resistant prostate cancer (CRPC). Its distinct phenotype is characterized by an aggressive clinical course, lack of responsiveness to hormonal therapies and poor prognosis. Importantly, a subset of CRPC patients exhibits an aggressive-variant disease with very similar clinical and molecular characteristics to small-cell prostate cancer (SCPC) even though tumors do not have NE differentiation. This aggressive-variant prostate cancer (AVPC) also shares the sensitivity of SCPC to platinum-based chemotherapy albeit with short-lived clinical benefit. As optimal treatment strategies for AVPC remain elusive, currently ongoing research efforts aim to enhance our understanding of the biology of this disease entity and improve treatment outcomes for our patients. This review is an overview of our current knowledge on prostate cancer with NE differentiation and AVPC, with a focus on their clinical characteristics and management, including available as well as experimental therapeutic strategies.
Language	English
Publishing date	2020-12-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12123792
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Article ; Online: Association Between Perioperative Chemotherapy and Survival in Men Undergoing Radical Resection for Primary Urethral Urothelial Carcinoma: An Analysis of the National Cancer Database.

Celtik, Kenan / Lim, Kelvin / Dursun, Furkan / Xu, Jiaqiong / Klaassen, Zachary / Zhang, Jun / Efstathiou, Eleni / Sonpavde, Guru / Wallis, Christopher / Satkunasivam, Raj

Clinical genitourinary cancer

2022 Volume 20, Issue 3, Page(s) 244–251

Abstract: 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 ...

Abstract	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. We compared OS between patients who had received peri-operative neoadjuvant (NAC) or adjuvant (AC) chemotherapy and those who had not using Kaplan-Meier curves and multivariable Cox proportional hazards regression model. Results: A total of 191 patients met inclusion criteria. 113 patients (59.2%) did not receive chemotherapy, while 39 (20.4%) and 39 (20.4%) received NAC and AC, respectively. Median follow-up was 28.0 months. Upon multivariable analysis, receipt of NAC (HR 0.50, 95% CI 0.28-0.91, P = .02) decreased the risk of all-cause mortality, while receipt of AC (HR 0.76, 95% CI 0.41-1.41) was not significantly associated with an OS benefit, as compared to no chemotherapy. Conclusion: Our study is the first to evaluate treatment specific outcomes in male patients with primary carcinoma of the urethra. We observed that neoadjuvant chemotherapy in men with UUC was associated with OS benefit. The utilization of NAC may improve survival, consistent with urothelial carcinoma of the bladder.
MeSH term(s)	Carcinoma, Transitional Cell/drug therapy ; Carcinoma, Transitional Cell/pathology ; Carcinoma, Transitional Cell/surgery ; Chemotherapy, Adjuvant ; Cystectomy ; Humans ; Male ; Neoadjuvant Therapy ; Retrospective Studies ; Urethral Neoplasms/drug therapy ; Urethral Neoplasms/surgery ; Urinary Bladder Neoplasms/drug therapy ; Urinary Bladder Neoplasms/pathology ; Urinary Bladder Neoplasms/surgery
Language	English
Publishing date	2022-01-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	2225121-2
ISSN	1938-0682 ; 1558-7673
ISSN (online)	1938-0682
ISSN	1558-7673
DOI	10.1016/j.clgc.2022.01.011
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Zs.A 6168: Show issues

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Article ; Online: Prostate Cancer Liver Metastases Presenting as Relatively Photopenic Lesions on 18F-Fluciclovine PET/CT.

Baiomy, Ali / Martiniova, Lucia / Efstathiou, Eleni / Schuster, David M / Ravizzini, Gregory

Clinical nuclear medicine

2020 Volume 46, Issue 4, Page(s) e240–e241

Abstract: Abstract: A 66-year-old man with prostate adenocarcinoma status post radical retropubic prostatectomy and bilateral pelvic lymph node dissection, followed by salvage external beam radiation therapy to the prostate bed 1 year after surgery. Over the ... ...

Abstract	Abstract: A 66-year-old man with prostate adenocarcinoma status post radical retropubic prostatectomy and bilateral pelvic lymph node dissection, followed by salvage external beam radiation therapy to the prostate bed 1 year after surgery. Over the course of 17 years, the patient underwent multiple lines of systemic treatment for recurrent disease. He was referred for restaging 18F-fluciclovine PET/CT due to rising serum prostate-specific antigen levels. Contrast-enhanced 18F-fluciclovine PET/CT images demonstrated multiple new liver metastases, which were relatively photopenic in comparison with the physiologic radiotracer activity in the surrounding normal liver parenchyma.
MeSH term(s)	Aged ; Carboxylic Acids ; Cyclobutanes ; Humans ; Liver Neoplasms/diagnostic imaging ; Liver Neoplasms/secondary ; Male ; Neoplasm Staging ; Positron Emission Tomography Computed Tomography/methods ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/blood ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/surgery ; Salvage Therapy
Chemical Substances	Carboxylic Acids ; Cyclobutanes ; fluciclovine F-18 (38R1Q0L1ZE) ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2020-10-07
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	197628-x
ISSN	1536-0229 ; 0363-9762
ISSN (online)	1536-0229
ISSN	0363-9762
DOI	10.1097/RLU.0000000000003377
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Zs.A 1276: Show issues

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Article ; Online: Nadir Prostate-specific Antigen as an Independent Predictor of Survival Outcomes: A Post Hoc Analysis of the PROSPER Randomized Clinical Trial.

Hussain, Maha / Sternberg, Cora N / Efstathiou, Eleni / Fizazi, Karim / Shen, Qi / Lin, Xun / Sugg, Jennifer / Steinberg, Joyce / Noerby, Bettina / De Giorgi, Ugo / Shore, Neal D / Saad, Fred

The Journal of urology

2023 Volume 209, Issue 3, Page(s) 532–539

Abstract: 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 ... ...

Abstract	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. Metastasis-free survival (primary endpoint) and overall survival (secondary endpoint) were evaluated for 4 mutually exclusive subgroups defined by PSA decline: <50% (reference); ≥50% to <90%; ≥90%, nadir ≥0.2 ng/mL; and ≥90%, nadir <0.2 ng/mL. Medians and 95% confidence intervals were determined using a 12-month landmark analysis; hazard ratios and Results: In enzalutamide-treated men, PSA declines of <50%, ≥50% to <90%, ≥90% with nadir ≥0.2 ng/mL, and ≥90% with nadir <0.2 ng/mL were associated with median metastasis-free survival in months (95% confidence intervals) of 22.1 (14.8-not reached), 34.2 (29.4-not reached), 36.6 (33.4-not reached), and not reached, respectively, and overall survival in months (95% confidence intervals) of 40.8 (31.7-44.9), 54.4 (49.0-67.0), 64.3 (63.4-not reached), and not reached, respectively. Conclusions: There was a statistically significant correlation between greater depth of PSA decline and improved clinical outcomes, suggesting a previously underappreciated relationship between changes in PSA levels and clinical outcomes in nonmetastatic castration-resistant prostate cancer.
MeSH term(s)	Humans ; Male ; Androgen Antagonists/therapeutic use ; Antineoplastic Agents/therapeutic use ; Nitriles/therapeutic use ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/diagnosis ; Prostatic Neoplasms, Castration-Resistant/pathology ; Treatment Outcome
Chemical Substances	Androgen Antagonists ; Antineoplastic Agents ; enzalutamide (93T0T9GKNU) ; Nitriles ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2023-02-09
Publishing country	United States
Document type	Clinical Trial, Phase III ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	3176-8
ISSN	1527-3792 ; 0022-5347
ISSN (online)	1527-3792
ISSN	0022-5347
DOI	10.1097/JU.0000000000003084
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Ui VI Zs.91: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 331: Show issues

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Article ; Online: Plain language summary: Can declines in prostate-specific antigen level indicate how long patients with advanced prostate cancer will live when treated with enzalutamide?

Hussain, Maha / Sternberg, Cora N / Efstathiou, Eleni / Fizazi, Karim / Shen, Qi / Lin, Xun / Sugg, Jennifer / Steinberg, Joyce / Noerby, Bettina / Giorgi, Ugo De / Shore, Neal D / Saad, Fred

Future oncology (London, England)

2023 Volume 19, Issue 29, Page(s) 1953–1960

Abstract: What is this summary about?: This is a summary of a research article originally published in the : What were the results?: Researchers found that patients with a large decline in PSA level after treatment were more likely to live longer and without ... ...

Abstract	What is this summary about?: This is a summary of a research article originally published in the What were the results?: Researchers found that patients with a large decline in PSA level after treatment were more likely to live longer and without their cancer spreading. What do the results mean?: This study shows a link between PSA level changes and how long patients with nmCRPC live when treated with enzalutamide and ADT. These results may help health professionals monitor patients with different PSA level changes after enzalutamide treatment. Patients with a large decline in PSA level may not need to be monitored as closely as patients with a small decline in PSA level.
Language	English
Publishing date	2023-08-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2023-0135
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Zs.A 6478: Show issues

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Article ; Online: Monitoring Glucocorticoid Receptor in Plasma-derived Extracellular Vesicles as a Marker of Resistance to Androgen Receptor Signaling Inhibition in Prostate Cancer.

Gentile, Emanuela / Hahn, Andrew W / Song, Jian H / Hoang, Anh / Shepherd, Peter D A / Ramachandran, Sumankalai / Navone, Nora M / Efstathiou, Eleni / Titus, Mark / Corn, Paul G / Lin, Sue-Hwa / Logothetis, Christopher J / Panaretakis, Theocharis

Cancer research communications

2023 Volume 3, Issue 12, Page(s) 2531–2543

Abstract: 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 ... ...

Abstract	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. Plasma-derived EVs were isolated from patients with localized high-risk prostate cancer undergoing androgen ablation. The mRNA levels of GR in EVs and their responsive genes were detected by transcriptome analysis, qRT-PCR and the protein levels by Western blot analysis. We detected changes in GR expression at mRNA and protein levels in EVs derived from LNCaP and LREX cells in in vitro studies. In in vivo experiments, LNCaP and the PDX MDA 322-2-6a-bearing mice were treated with enzalutamide. GR levels in plasma-derived EVs were increased only in those tumors that did not respond to enzalutamide. Treatment of mice bearing enzalutamide-resistant tumors with a GR inhibitor in combination with enzalutamide led to a transient pause in tumor growth in a subset of tumors and decreased GR levels intracellular and in plasma-derived EVs. In a subgroup of patients with high-risk localized prostate cancer treated with androgen signaling inhibition, GR was found upregulated in matching tissue and plasma EVs. These analyses showed that GR levels in plasma-derived EVs may be used for monitoring the transition of GR expression allowing for early detection of resistance to androgen ablation treatment. Significance: Longitudinal monitoring of GR expression in plasma-derived EVs from patients with prostate cancer treated with androgen signaling inhibitors facilitates early detection of acquisition of resistance to androgen receptor signaling inhibition in individual patients.
MeSH term(s)	Receptors, Glucocorticoid/blood ; Receptors, Glucocorticoid/genetics ; Extracellular Vesicles/metabolism ; Biomarkers/blood ; Signal Transduction ; Humans ; Animals ; Mice ; Male ; Cell Line, Tumor ; Phenylthiohydantoin/pharmacology ; Antineoplastic Agents/pharmacology ; Drug Resistance, Neoplasm/drug effects ; Gene Expression Regulation/drug effects ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/genetics ; Mifepristone/pharmacology
Chemical Substances	Receptors, Glucocorticoid ; Biomarkers ; enzalutamide (93T0T9GKNU) ; Phenylthiohydantoin (2010-15-3) ; Antineoplastic Agents ; Mifepristone (320T6RNW1F)
Language	English
Publishing date	2023-11-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2767-9764
ISSN (online)	2767-9764
DOI	10.1158/2767-9764.CRC-23-0362
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