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Article ; Online: Cardiovascular Toxicity Associated With Androgen Receptor Axis-Targeted Agents in Patients With Prostate Cancer: A Meta-analysis of Randomized Controlled Trials.

Zhou, Susu / Alerasool, Parissa / Kishi, Noriko / Joshi, Himanshu / Sahni, Gagan / Tsao, Che-Kai

2024 , Page(s) 102066

Abstract: Introduction: Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains unknown about the potential cardiovascular toxicities.: Patients and ... ...

Abstract	Introduction: Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains unknown about the potential cardiovascular toxicities. Patients and methods: We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for randomized controlled trials of patients receiving ARAT agents for PC from inception to March 2023. The odds ratios (ORs) of all-grade and high-grade cardiovascular adverse events (CVAEs) for patients treated with and without ARAT agents were pooled for meta-analysis. Subgroup analyses based on PC type and treatment regimen were conducted. Results: A total of 15 double-blind placebo-controlled phase 3 trials comprising 15,842 patients were included. In addition to hot flush and hypertension of any degree of severity, inclusion of ARAT agents was associated with a significantly higher risk of acute myocardial infarction (OR: 1.96, 95% CI: 1.05-3.68, P = .04), myocardial infarction (OR: 2.44, 95% CI: 1.27-4.66, P = .007) and angina pectoris (OR: 2.00, 95% CI: 1.00-4.02, P = .05). With regard to individual ARAT agents, enzalutamide was associated with a significantly higher risk of acute myocardial infarction (OR: 3.11, 95% CI: 1.17-8.28, P = .02), coronary artery disease (OR: 8.33, 95% CI: 1.54-44.95, P = .01), and high-grade hypertension (OR: 4.94, 95% CI: 1.11-22.06, P = .04), while abiraterone and apalutamide were associated with a significantly higher risk of angina pectoris (OR: 5.48, 95% CI: 1.23-24.33, P = .03) and myocardial infarction (OR: 7.00, 95% CI: 1.60-30.62, P = .01), respectively. Conclusion: The inclusion of ARAT agents was associated with a significantly higher risk of several CVAEs. Clinicians should remain vigilant, both in pre-treatment screening and monitoring for clinical symptoms and signs, when considering ARAT agent particularly for patients with pre-existing risk factors.
Language	English
Publishing date	2024-03-08
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.2024.102066
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Zs.A 6168: Show issues

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Article ; Online: First-Line Treatment of Hormone-Sensitive Metastatic Prostate Cancer: Is There a Single Standard of Care?

Tsao, Che-Kai / Oh, William K

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2018 Volume 36, Issue 11, Page(s) 1060–1061

MeSH term(s)	Androgen Antagonists ; Humans ; Male ; Prostatic Neoplasms ; Standard of Care ; Survival Analysis
Chemical Substances	Androgen Antagonists
Language	English
Publishing date	2018-02-12
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2017.77.4315
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Zs.A 1847: 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 650: Show issues

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Article ; Online: Clinical outcomes, management, and treatment patterns in patients with metastatic castration-resistant prostate cancer treated with radium-223 in community compared to academic settings.

Sartor, Oliver / Appukkuttan, Sreevalsa / Weiss, Jeffrey / Tsao, Che-Kai

The Prostate

2021 Volume 81, Issue 10, Page(s) 657–666

Abstract: Background: The most common site of disease in metastatic castration-resistant prostate cancer (mCRPC) is the bone. The ALSYMPCA study demonstrated that radium-223 significantly improved overall survival (OS) in mCRPC patients with symptomatic bone ... ...

Abstract	Background: The most common site of disease in metastatic castration-resistant prostate cancer (mCRPC) is the bone. The ALSYMPCA study demonstrated that radium-223 significantly improved overall survival (OS) in mCRPC patients with symptomatic bone metastases and without visceral metastases. However, administration requires a multidisciplinary approach and an infrastructure that supports coordination of care, which may differ by practice site. We aimed to evaluate practice patterns and treatment outcomes in patients with mCRPC treated at a community practice (CP) compared with those treated at an academic center (AC). Methods: This retrospective review included 200 adult mCRPC patients receiving radium-223 between January 2014 and June 2017. The primary endpoint, OS, was estimated from the date of radium-223 initiation. Secondary outcomes included a comparison of baseline characteristics, reasons for initiation and discontinuation of radium-223, and treatment sequencing. A subset analysis of OS based on the number of radium-223 doses and on sequencing of radium-223 either before or after chemotherapy was also conducted. Results: Most patients were treated at a CP (57%). Patients treated at CP sites were significantly older (74.9 vs. 71.9 years; p = .031) and had more comorbidities (Klabunde score 1.1 vs. 0.7; p = .020) than those in an AC but initiated treatment within a shorter period of time from diagnosis of mCRPC (1.3 vs. 1.9 years; p < .001) and received a greater mean number of radium-223 doses (5.4 vs. 4.8; p = .001). There were no observed differences in OS between CPs versus ACs (21.6 vs. 20.7 months; p = .306). Overall, patients who received 5-6 doses versus 1-4 doses of radium-223 had a longer median OS (23.3 vs. 6.4 months; p < .001). The most common reason for discontinuation in patients who did not complete treatment was disease progression. Overall, 43% of patients received radium-223 monotherapy and 57% concurrently with other agents. Conclusions: Most patients received radium-223 concurrently with abiraterone acetate or enzalutamide and were able to complete 5-6 doses of radium-223. Despite differences in the populations and treatment patterns, no survival differences between patients treated in ACs versus CPs were observed. Additional real-world data are needed to validate these findings.
MeSH term(s)	Academic Medical Centers/methods ; Academic Medical Centers/trends ; Aged ; Aged, 80 and over ; Bone Neoplasms/diagnosis ; Bone Neoplasms/radiotherapy ; Bone Neoplasms/secondary ; Community Health Services/methods ; Community Health Services/trends ; Disease Management ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms, Castration-Resistant/diagnosis ; Prostatic Neoplasms, Castration-Resistant/radiotherapy ; Radium/therapeutic use ; Retrospective Studies ; Survival Rate/trends ; Treatment Outcome
Chemical Substances	Radium-223 (8BR2SOL3L1) ; Radium (W90AYD6R3Q)
Language	English
Publishing date	2021-05-12
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604707-5
ISSN	1097-0045 ; 0270-4137
ISSN (online)	1097-0045
ISSN	0270-4137
DOI	10.1002/pros.24143
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Zs.A 1608: Show issues

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Article ; Online: Risk Factors for Early Treatment Discontinuation Due to Toxicity Among Patients With Metastatic Castration-resistant Prostate Cancer Receiving Androgen Receptor-targeted Therapy.

Chakrani, Zakaria / Mellgard, George / Saffran, Nathaniel / McCroskery, Stephen / Taylor, Nicole / Patel, Mann / Liaw, Bobby / Galsky, Matthew / Oh, William K / Tsao, Che-Kai / Patel, Vaibhav G

American journal of clinical oncology

2024

Abstract: Background: Androgen receptor-targeted therapies (ARTs) improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC); however, a significant portion of patients discontinue treatment for various reasons including ... ...

Abstract	Background: Androgen receptor-targeted therapies (ARTs) improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC); however, a significant portion of patients discontinue treatment for various reasons including treatment-related toxicity. We aim to describe reasons for ART treatment discontinuation and identify predictors associated with increased risk of treatment discontinuation due to toxicity. Methods: We performed a single-institution retrospective review of patients with mCRPC receiving ART between 2010 and 2021. Our primary aim was to identify risk factors for treatment discontinuation due to toxicity. Our secondary aim was to describe ART discontinuation patterns among patients with mCRPC. Results: One hundred thirty-three patients with mCRPC started and discontinued ARTs. Fourteen patients (10.5%) discontinued treatment due to toxicity. Common reasons for treatment discontinuation include Prostate Specific Antigen test progression, radiographic progression, toxicity, and death. Significant predictors of treatment discontinuation due to toxicity on bivariate analysis and multivariate analysis included patient-reported falls (odds ratio [OR]: 7.67, CI: [1.31-40.42]; P=0.016), rash (OR: 13.4, CI: [1.35-134.81]; P=0.026), and weakness (OR: 4.16, CI: [1.15-15.0]; P=0.019). Conclusions: Our work presents the first description of ART treatment discontinuation and its causes in the real-world setting, as well as patient-reported side effects. Most patients with mCRPC discontinued treatment due to the progression of disease and a minority of patients discontinued secondary to treatment toxicity. Initial multivariable analysis suggests that patient-reported weakness, falls, and rash were associated with a higher likelihood of treatment discontinuation due to toxicity. Early monitoring of this population can prolong the duration of treatment and prevent unnecessary treatment burden.
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	604536-4
ISSN	1537-453X ; 0277-3732
ISSN (online)	1537-453X
ISSN	0277-3732
DOI	10.1097/COC.0000000000001087
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Zs.A 1557: Show issues

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Article ; Online: From Bench to Bedside

Jonathan Anker / Justin Miller / Nicole Taylor / Natasha Kyprianou / Che-Kai Tsao

Cells, Vol 10, Iss 3231, p

How the Tumor Microenvironment Is Impacting the Future of Immunotherapy for Renal Cell Carcinoma

2021 Volume 3231

Abstract: Immunotherapy has revolutionized the treatment landscape for many cancer types. The treatment for renal cell carcinoma (RCC) has especially evolved in recent years, from cytokine-based immunotherapies to immune checkpoint inhibitors. Although clinical ... ...

Abstract	Immunotherapy has revolutionized the treatment landscape for many cancer types. The treatment for renal cell carcinoma (RCC) has especially evolved in recent years, from cytokine-based immunotherapies to immune checkpoint inhibitors. Although clinical benefit from immunotherapy is limited to a subset of patients, many combination-based approaches have led to improved outcomes. The success of such approaches is a direct result of the tumor immunology knowledge accrued regarding the RCC microenvironment, which, while highly immunogenic, demonstrates many unique characteristics. Ongoing translational work has elucidated some of the mechanisms of response, as well as primary and secondary resistance, to immunotherapy. Here, we provide a comprehensive review of the RCC immunophenotype with a specific focus on how preclinical and clinical data are shaping the future of immunotherapy.
Keywords	renal cell carcinoma ; tumor microenvironment ; immunology ; immunotherapy ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: From Bench to Bedside: How the Tumor Microenvironment Is Impacting the Future of Immunotherapy for Renal Cell Carcinoma.

Anker, Jonathan / Miller, Justin / Taylor, Nicole / Kyprianou, Natasha / Tsao, Che-Kai

Cells

2021 Volume 10, Issue 11

Abstract	Immunotherapy has revolutionized the treatment landscape for many cancer types. The treatment for renal cell carcinoma (RCC) has especially evolved in recent years, from cytokine-based immunotherapies to immune checkpoint inhibitors. Although clinical benefit from immunotherapy is limited to a subset of patients, many combination-based approaches have led to improved outcomes. The success of such approaches is a direct result of the tumor immunology knowledge accrued regarding the RCC microenvironment, which, while highly immunogenic, demonstrates many unique characteristics. Ongoing translational work has elucidated some of the mechanisms of response, as well as primary and secondary resistance, to immunotherapy. Here, we provide a comprehensive review of the RCC immunophenotype with a specific focus on how preclinical and clinical data are shaping the future of immunotherapy.
MeSH term(s)	Biomarkers, Tumor/metabolism ; Carcinoma, Renal Cell/immunology ; Carcinoma, Renal Cell/therapy ; Humans ; Immunotherapy ; Kidney Neoplasms/immunology ; Kidney Neoplasms/therapy ; Models, Biological ; Translational Research, Biomedical ; Tumor Microenvironment
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2021-11-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10113231
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Article ; Online: COVID-19 vaccination: Prioritization of at risk groups.

Lundon, Dara J / Khusid, Johnathan A / Tsao, Che-Kai / Patel, Vaibhav / Kyprianou, Natasha / Tewari, Ashutosh / Wiklund, Peter

Urologic oncology

2021 Volume 39, Issue 7, Page(s) 375–378

Language	English
Publishing date	2021-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1336505-8
ISSN	1873-2496 ; 1078-1439
ISSN (online)	1873-2496
ISSN	1078-1439
DOI	10.1016/j.urolonc.2021.03.021
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Zs.A 4817: Show issues

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Article ; Online: Prostate cancer in transgender women: considerations for screening, diagnosis and management.

Crowley, Fionnuala / Mihalopoulos, Meredith / Gaglani, Simita / Tewari, Ashutosh K / Tsao, Che-Kai / Djordjevic, Miroslav / Kyprianou, Natasha / Purohit, Rajveer S / Lundon, Dara J

British journal of cancer

2022 Volume 128, Issue 2, Page(s) 177–189

Abstract: Transgender individuals represent 0.55% of the US population, equivalent to 1.4 million transgender adults. In transgender women, feminisation can include a number of medical and surgical interventions. The main goal is to deprive the phenotypically ... ...

Abstract	Transgender individuals represent 0.55% of the US population, equivalent to 1.4 million transgender adults. In transgender women, feminisation can include a number of medical and surgical interventions. The main goal is to deprive the phenotypically masculine body of androgens and simultaneously provide oestrogen therapy for feminisation. In gender-confirming surgery (GCS) for transgender females, the prostate is usually not removed. Due to limitations of existing cohort studies, the true incidence of prostate cancer in transgender females is unknown but is thought to be less than the incidence among cis-gender males. It is unclear how prostate cancer develops in androgen-deprived conditions in these patients. Six out of eleven case reports in the literature presented with metastatic disease. It is thought that androgen receptor-mediated mechanisms or tumour-promoting effects of oestrogen may be responsible. Due to the low incidence of prostate cancer identified in transgender women, there is little evidence to drive specific screening recommendations in this patient subpopulation. The treatment of early and locally advanced prostate cancer in these patients warrants an individualised thoughtful approach with input from patients' reconstructive surgeons. Both surgical and radiation treatment for prostate cancer in these patients can profoundly impact the patient's quality of life. In this review, we discuss the evidence surrounding screening and treatment of prostate cancer in transgender women and consider the current gaps in our knowledge in providing evidence-based guidance at the molecular, genomic and epidemiological level, for clinical decision-making in the management of these patients.
MeSH term(s)	Male ; Adult ; Humans ; Transgender Persons ; Feminization/drug therapy ; Quality of Life ; Early Detection of Cancer ; Prostatic Neoplasms/therapy ; Prostatic Neoplasms/drug therapy ; Estrogens/therapeutic use
Chemical Substances	Estrogens
Language	English
Publishing date	2022-10-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-022-01989-y
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Uh III Zs.142: Show issues

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Article ; Online: Biomarker Development Trial of Satraplatin in Patients with Metastatic Castration-Resistant Prostate Cancer.

Liaw, Bobby C / Tsao, Che-Kai / Seng, Sonia / Jun, Tomi / Gong, Yixuan / Galsky, Matthew D / Oh, William K

The oncologist

2022 Volume 28, Issue 4, Page(s) 366–e224

Abstract: Background: In the phase III SPARC trial, satraplatin, an oral platinum analogue, demonstrated anticancer activity in men with metastatic castration-resistant prostate cancer (mCRPC). Repeat biopsies are uncommon in mCRPC, limiting the feasibility of ... ...

Abstract	Background: In the phase III SPARC trial, satraplatin, an oral platinum analogue, demonstrated anticancer activity in men with metastatic castration-resistant prostate cancer (mCRPC). Repeat biopsies are uncommon in mCRPC, limiting the feasibility of tissue-based biomarkers. This phase II study sought to evaluate the feasibility and utility of blood-based biomarkers to identify platinum-sensitive mCRPC. Methods: Patients with mCRPC who had progressed on docetaxel were enrolled at a single center from 2011 to 2013. Subjects received satraplatin 80 mg/m2 by mouth daily on days 1-5 and prednisone 5 mg PO twice daily, on a 35-day cycle. Serial peripheral blood samples were collected for biomarker assessment. Results: Thirteen docetaxel-refractory mCRPC patients were enrolled, with a median age of 69 years (range 54-77 years) and median PSA of 71.7 ng/mL (range 0.04-3057). Four of 13 patients (31%) responded to satraplatin (defined as a PSA decline of ≥30%). Responders demonstrated improved time to disease progression (206 vs. 35 days, HR 0.26, 95% CI, 0.02-0.24, P = .003). A 6-gene peripheral blood RNA signature and serum tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were assessed as biomarkers, but neither was significantly associated with response to satraplatin. Conclusion: In this small series, one-third of mCRPC patients responded to platinum-based chemotherapy. Peripheral blood biomarker measurement is feasible in mCRPC, though the biomarkers we investigated were not associated with platinum response. Other biomarkers, such as DNA damage repair mutations, should be evaluated.
MeSH term(s)	Male ; Humans ; Middle Aged ; Aged ; Docetaxel ; Prostatic Neoplasms, Castration-Resistant/pathology ; Prostate-Specific Antigen ; Tissue Inhibitor of Metalloproteinase-1/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome
Chemical Substances	Docetaxel (15H5577CQD) ; satraplatin (8D7B37T28G) ; Prostate-Specific Antigen (EC 3.4.21.77) ; Tissue Inhibitor of Metalloproteinase-1
Language	English
Publishing date	2022-12-12
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyac224
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Zs.A 4845: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 494: Show issues

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Article ; Online: Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer.

Chen, Tzu-Yi / Mihalopoulos, Meredith / Zuluaga, Laura / Rich, Jordan / Ganta, Teja / Mehrazin, Reza / Tsao, Che-Kai / Tewari, Ash / Gonzalez-Kozlova, Edgar / Badani, Ketan / Dogra, Navneet / Kyprianou, Natasha

International journal of molecular sciences

2023 Volume 24, Issue 19

Abstract: Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been ... ...

Abstract	Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.
MeSH term(s)	Male ; Humans ; Carcinoma, Renal Cell/pathology ; Prostate/pathology ; Prostatic Neoplasms, Castration-Resistant/pathology ; Clinical Relevance ; Kidney Neoplasms/metabolism ; Neoplasm Recurrence, Local/pathology ; Extracellular Vesicles/metabolism ; Exosomes/metabolism
Language	English
Publishing date	2023-09-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241914713
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