Metastatic Castration-Resistant Prostate Cancer: Academic Insights and Perspectives Analysis

2019 ◽  
Author(s):  
Lugeng He ◽  
Hui Fang ◽  
Chao Chen ◽  
Yanqi Wu ◽  
Yuyong Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Developed Countries ◽  
The United States ◽  
Vital Role ◽  
Cancer Center ◽  
Castration Resistant Prostate Cancer ◽  
Research Areas ◽  
Castration Resistant ◽  
The Usa ◽  
Future Direction

Abstract Background In recent years, metastatic castration-resistant prostate cancer (MCRPC) and studies related to MCRPC have drawn global attention. The main objective of this bibliometric study was to provide an overview of MCRPC, explore clusters and trends in research and investigate the future direction of MCRPC research. Methods A total of 4,089 publications published between 1979 and 2018 were retrieved from the Web of Science (WoS) Core Collection database. Different aspects of MCRPC research, including the countries/territories, institutions, journals, authors, research areas, funding agencies and author keywords, were analyzed. Results The number of annual MCRPC publications increased rapidly after 2010. American researchers played a vital role in this increase, as they published the most publications. The most productive institution was Memorial Sloan Kettering Cancer Center. De Bono, JS (the United Kingdom [UK]) and Scher, HI (the United States of America [USA]) were the two most productive authors. The National Institutes of Health (NIH) funded the largest number of published papers. Analyses of keywords suggested that therapies (abiraterone, enzalutamide, etc.) would attracted global attention after US Food and Drug Administration (FDA) approval. Conclusions Developed countries, especially the USA,were the leading nations for MCRPC research because of their abundant funding and frequent international collaborations. Therapy was one of the most vital aspects of MCRPC research. Therapies targeting DNA repair or the androgen receptor (AR) signing pathway and new therapies especially prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) would be the next focus of MCRPC research.

The 100 most-cited articles in castration-resistant prostate cancer: a bibliometric analysis

2021 ◽  
Keyword(s):  
Cancer Research ◽  
Bibliometric Analysis ◽  
Future Research ◽  
Castration Resistant Prostate Cancer ◽  
Research Areas ◽  
Castration Resistant ◽  
The Usa ◽  
Future Research Directions ◽  
Different Characteristics ◽  
Number Of Citations

Purpose: To assess the present landscape and future research directions, a bibliometric analysis was performed to identify the characteristics of the 100 most-cited articles (T100 articles) on CRPC research. Methods: A list of the T100 articles investigating CRPC was generated by searching the Web of Science (WoS) Core Collection database. Different characteristics of the T100 articles, including the countries/territories, journals, authors, and research areas, were analyzed. Results: The number of citations of T100 articles published between 1992 and 2017 ranged from 282 to 3594, with an average of 654.9 citations. According to the topic of the article, ''Mechanisms related to tumor progression or metastasis'' ranked first with 41 T100 articles, while immunotherapy ranked fourth with 7 T100 articles. The T100 articles originated from 31 countries, with more than half originating from the USA (n = 89). Professor Scher HI published the most T100 articles as the first author (4) and as the corresponding author (5), while Pro De Bono JS from the Institute of Cancer Research published 3 articles as the first author and 8 articles as the corresponding author. The journal Cancer Research published 20 T100 articles with a total of 8946 citations. The number of T100 articles(r = 0.485, P = 0.01) and the total number of citations(r = 0.626, P < 0.001) were all positively correlated with the IF of the journal. Conclusions: This analysis offers a historical perspective on the progress and attempts to reveal future trends in CRPC research using bibliometric analysis. This study's results suggest that immunotherapy and the study of androgen receptors as well as their signaling axes will possibly be hot topics and trends in CRPC research.

scholarly journals Treatment characteristics for nonmetastatic castration-resistant prostate cancer in the United States, Europe and Japan

2019 ◽  
Vol 15 (35) ◽  
pp. 4069-4081 ◽  
Author(s):  
Ruchitbhai Shah ◽  
Marc Botteman ◽  
Reginald Waldeck
Keyword(s):  
Prostate Cancer ◽  
Eastern Cooperative Oncology Group ◽  
Patient Characteristics ◽  
The United States ◽  
Treatment Patterns ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Synthesis ◽  
Castration Resistant ◽  
The Us ◽  
Androgen Synthesis Inhibitors

Aim: We conducted this study to describe nonmetastatic castration-resistant prostate cancer (nmCRPC) patient characteristics and treatment patterns in the US, Europe and Japan. Materials & methods: Descriptive analyses were conducted using the 2015–2017 Ipsos Global Oncology Monitor Database. Results: A total of 2065 (442 in the US, 509 in Europe and 1114 in Japan) patients (median age: 74–80 years; stage III at diagnosis : 38.5%; Eastern Cooperative Oncology Group [ECOG] score ≤1: 79.4%; treated by urologist : 88.4%) were included in the analytic cohort. Luteinizing hormone-releasing hormone agonists and antiandrogens were the most commonly used first regimen treatments. With subsequent nmCRPC regimens their use decreased, while the use of chemotherapy, corticosteroids, androgen synthesis inhibitors and second-generation androgen receptor inhibitors increased. Conclusion: These data represent real-world treatment patterns in nmCRPC.

scholarly journals Androgen biosynthesis in castration-resistant prostate cancer

2014 ◽  
Vol 21 (4) ◽  
pp. T67-T78 ◽  
Author(s):  
Trevor M Penning
Keyword(s):  
Prostate Cancer ◽  
Enzyme Inhibitors ◽  
Molecular Medicine ◽  
Adult Males ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Patient Will ◽  
The Usa ◽  
Fatal Form ◽  
Low Levels

Prostate cancer is the second leading cause of death in adult males in the USA. Recent advances have revealed that the fatal form of this cancer, known as castration-resistant prostate cancer (CRPC), remains hormonally driven despite castrate levels of circulating androgens. CRPC arises as the tumor undergoes adaptation to low levels of androgens by either synthesizing its own androgens (intratumoral androgens) or altering the androgen receptor (AR). This article reviews the major routes to testosterone and dihydrotestosterone synthesis in CRPC cells and examines the enzyme targets and progress in the development of isoform-specific inhibitors that could block intratumoral androgen biosynthesis. Because redundancy exists in these pathways, it is likely that inhibition of a single pathway will lead to upregulation of another so that drug resistance would be anticipated. Drugs that target multiple pathways or bifunctional agents that block intratumoral androgen biosynthesis and antagonize the AR offer the most promise. Optimal use of enzyme inhibitors or AR antagonists to ensure maximal benefits to CRPC patients will also require application of precision molecular medicine to determine whether a tumor in a particular patient will be responsive to these treatments either alone or in combination.

Presence of myeloid-derived suppressor cells (MDSC) in patients with metastatic castration-sensitive and castration-resistant prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 222-222 ◽  
Author(s):  
Karen A. Autio ◽  
Phillip Wong ◽  
Angel Rabinowitz ◽  
Jianda Yuan ◽  
Lauryn Michelle Slavin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Whole Blood ◽  
Geometric Mean ◽  
Suppressor Cells ◽  
Current Treatment ◽  
Clinical State ◽  
Cancer Center ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

222 Background: MDSC contribute to an immune suppressive environment and have been implicated in cancer progression. Measurement (identification and enumeration) is challenged by the lack of analytically valid assays limiting data interpretation between groups. This impacts our understanding of rationale immune targets and design of clinical trials. We employed a novel biomarker based assay in whole blood to enumerate MDSC from patients with metastatic castration sensitive (CSPC) and castration resistant prostate cancer (CRPC). Methods: Whole blood was collected in Cyto-Chex (Streck) tubes. A published computational algorithm-based approach (developed by Memorial Sloan Kettering Cancer Center and commercialized by Serametrix) was employed to determine the %MDSC-monocytic and coefficient of variance (CV=ratio of SD and geometric mean fluorescence intensity) to assess HLA-DR spread on CD14+CD11b cells. Samples were performed in duplicate. Clinical variables including clinical state, past and current treatment, metastatic sites, PSA, and standard prognostic markers were collected. Results: 36 pts with metastatic prostate cancer (29 CRPC; 7 CSPC) were included. Median (SD) %MDSC in 29 CRPC pts was 21.15 (5.33) and median (SD) CV was1.29 (0.25); 7 CSPC demonstrated a median (SD) %MDSC 19.15 (4.86) and median (SD) CV 1.22 (0.25). MDSC did not differ between chemotherapy exposed (n=13) and chemotherapy naive (n=16) CRPC (23.3 vs 19.5, p=ns). MDSC were not significantly higher in those with visceral mets, though a trend existed (20.3 vs 24.0, p=0.076). PSA did not appear to correlate with MDSC or CV. Conclusions: Understanding the distribution and characterization of MDSC in various clinical states in prostate cancer is relevant to the development of immune targets in this disease. MDSC were quantifiable in both CSPC and CRPC. There was a trend for higher MDSC values in patients with visceral metastases, which historically are associated with worse prognoses. Presence of MDSC in metastatic CSPC and CRPC has important therapeutic and trial implications. Further discovery in larger cohorts and earlier disease states is underway.

scholarly journals PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer

2016 ◽  
Vol 113 (26) ◽  
pp. 7124-7129 ◽  
Author(s):  
Kanak Raina ◽  
Jing Lu ◽  
Yimin Qian ◽  
Martha Altieri ◽  
Deborah Gordon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Small Molecule ◽  
Xenograft Model ◽  
The United States ◽  
Castration Resistant Prostate Cancer ◽  
Secondary Resistance ◽  
Cellular Models ◽  
Castration Resistant ◽  
Mouse Xenograft Model ◽  
Bet Inhibitors

Prostate cancer has the second highest incidence among cancers in men worldwide and is the second leading cause of cancer deaths of men in the United States. Although androgen deprivation can initially lead to remission, the disease often progresses to castration-resistant prostate cancer (CRPC), which is still reliant on androgen receptor (AR) signaling and is associated with a poor prognosis. Some success against CRPC has been achieved by drugs that target AR signaling, but secondary resistance invariably emerges, and new therapies are urgently needed. Recently, inhibitors of bromodomain and extra-terminal (BET) family proteins have shown growth-inhibitory activity in preclinical models of CRPC. Here, we demonstrate that ARV-771, a small-molecule pan-BET degrader based on proteolysis-targeting chimera (PROTAC) technology, demonstrates dramatically improved efficacy in cellular models of CRPC as compared with BET inhibition. Unlike BET inhibitors, ARV-771 results in suppression of both AR signaling and AR levels and leads to tumor regression in a CRPC mouse xenograft model. This study is, to our knowledge, the first to demonstrate efficacy with a small-molecule BET degrader in a solid-tumor malignancy and potentially represents an important therapeutic advance in the treatment of CRPC.

scholarly journals Development of an immunofluorescent AR-V7 circulating tumor cell assay – A blood-based test for men with metastatic prostate cancer

2020 ◽  
Vol 9 (1) ◽  
pp. 13-19
Author(s):  
David Lu ◽  
Rachel Krupa ◽  
Melissa Harvey ◽  
Ryon P. Graf ◽  
Nicole Schreiber ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Control Cell ◽  
Circulating Tumor Cell ◽  
Cancer Center ◽  
Cell Detection ◽  
Castration Resistant Prostate Cancer ◽  
Nccn Guidelines ◽  
Castration Resistant ◽  
Validation Testing

Introduction: Here we describe the development of a protein immunofluorescent assay for the detection of nuclear-localized androgen receptor variant 7 (AR-V7) protein within circulating tumor cells (CTCs) identified in patient blood samples. Used in the clinic, the test result serves as a validated biomarker of futility for patients with progressing metastatic castration-resistant prostate cancer (mCRPC) who are treated with androgen receptor targeted therapies (AATT) in whom nuclear-localized AR-V7 CTCs are identified and have received level 2A evidence in the 2019 National Cancer Center Network (NCCN) guidelines (v1.0). Methods: Assay development was completed on the Epic Sciences rare cell detection platform using control cell lines of known AR-V7 status and clinical testing of mCRPC patient samples obtained at the decision point in management. Results and conclusions: Using these samples, all assay parameters, scoring criteria, and clinical cutoffs for positivity were prospectively selected and locked. After assay lock, blinded clinical validation testing was initiated on multiple, independent, clinical cohorts as reported by Scher et al (JAMA Oncol. 2016;2:1441-1449; JAMA Oncol. 2018;4:1179-1186) and Armstrong et al (J Clin Oncol. 2019;37:1120-1129).

The TRUMPET registry: Assessing clinical outcomes and quality of life in patients with castration-resistant prostate cancer and their caregivers.

2016 ◽  
Vol 34 (3_suppl) ◽  
pp. 241-241
Author(s):  
Scott C Flanders ◽  
Daniel W. Lin ◽  
Lawrence Ivan Karsh ◽  
Daniel H. Shevrin ◽  
Neal D. Shore ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Work Productivity ◽  
Patient Characteristics ◽  
The United States ◽  
Treatment Patterns ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

241 Background: Patient care in castration-resistant prostate cancer (CRPC) is complex, with varying treatment patterns due to differences in therapies, patient characteristics, and physician practices. The impact of such patterns on clinical outcomes and quality of life (QoL) represent a contemporary medical issue. This study aims to improve the understanding of clinical outcomes and QoL of patients with CRPC and their caregivers. Methods: TRUMPET is a prospective, observational, multi-center study of patients with CRPC in the United States. Approximately 2000 patients and their caregivers (if eligible) will be enrolled over 24 months from IRB-approved urology and oncology sites. Eligible patients with CRPC include those with life expectancy of ≥ 6 months initiating the first active course of anti-cancer treatment for M0 or M1. A 48-month observation period will follow the last patient enrolled. Primary objectives are to describe longitudinal patterns of care, disease assessment methods, treatment decisions, treatment settings, physician referral patterns, and CRPC patient characteristics associated with these. Patient-reported health-related QoL (HRQoL) instruments will assess the effects of CRPC and its management on patient perception of key aspects of HRQoL. The following will be administered at baseline and follow-up: SF-12v2 Health Survey, Functional Assessment of Cancer Therapy–Prostate, Brief Pain Inventory-Short Form, and Memorial Anxiety Scale for Prostate Cancer (prostate-specific antigen anxiety subscale). In a patient sub-study, work productivity and treatment satisfaction will be described using the Work Productivity and Activity Impairment (WPAI) Questionnaire: Specific Health Problem and Service Satisfaction Scale for Cancer Care. Caregiver QoL and productivity will be captured with the Caregiver Quality of Life Index–Cancer and the Caregiver-modified WPAI Questionnaire. Results: As of August 21, 2015, 60 sites were active, with 63 patients and 39 caregivers enrolled. Conclusions: Outcomes from the TRUMPET study will describe treatment patterns, QoL, and health care resources associated with patient management in CRPC. Clinical trial information: NCT02380274.

Comparison of enzalutamide versus abiraterone in castration-resistant prostate cancer before docetaxel: Results of a propensity score-matched analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16540-e16540
Author(s):  
Marcelle Goldner Cesca ◽  
Maysa Tamara Silveira ◽  
Natasha Carvalho Pandolfi ◽  
Thiago Bueno Oliveira ◽  
José Augusto Rinck ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Propensity Score ◽  
Cox Regression ◽  
Primary Objective ◽  
Rank Test ◽  
Cancer Center ◽  
Matched Cohort ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response

e16540 Background: Metastatic castration-resistant prostate cancer (mCRPC) phenotype involves androgen-receptor signalling mechanisms that support the use of enzalutamide (EZ) and abiraterone (Abi). These therapies improve overall survival (OS) and quality-of-life, with a favourable safety profile. There is no validated data defining the best drug or sequence to be used. Methods: A retrospective cohort of mCRPC patients (pts) was analysed at AC Camargo Cancer Center. The primary objective was to compare progression-free survival (PFS) and OS in patients treated with EZ or Abi as first line (docetaxel naïve pts). Kaplan-Meier, Log-Rank Test and Cox Regression were used for survival analysis. To address unbalanced characteristics between the two treatment groups treatment efficacy was compared in a propensity score matched cohort. Results: From May, 2002 to September, 2017, 120 pts were treated with Abi (84%) or EZ (36%). Median follow-up was 21.2 months. Median age at diagnosis was 66 (48-84), the majority were Gleason score 7 (34%) and median baseline PSA was 14. Median PFS was 17.4 months in EZ and 10.6 months in Abi group (HR = 0.65; 95%CI: 0.39-1.10; p = 0.11). Median OS was not reached and 31.6 months for EZ and Abi, respectively (HR = 0.60; 95%CI: 0.27-1.36; p = 0.22). EZ was associated with a better PSA response in the first 4 months of treatment (p < 0.001). Independent prognostic factors for worse OS and PFS were ECOG ≥ 1, treatment toxicity ≥ G1 and lower PSA doubling time before treatment and for better OS and PFS were PSA response in the first 4 months and alkaline phosphatase and lactate dehydrogenase response at any time. In the propensity score matched cohort including 72 patients PFS was better in EZ group (HR = 0.36; 95%CI: 0.20-0.64; p < 0.001) but there was no difference in OS (HR = 0.66; 95%CI: 0.27-1.63; p = 0.37). Conclusions: EZ was associated with prolonged PFS and better PSA response, with no OS improvement when compared with Abi for mCRPC before docetaxel, in a propensity score matched analysis.

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