Search Results (147)

This case report presents a rare occurrence of adrenal insufficiency induced by Zytiga (abiraterone acetate) in a patient with high-risk localized prostatic adenocarcinoma. Abiraterone acetate is a potent, selective and irreversible CYP17A1 inhibitor and is commonly used in the treatment of prostate cancer, but it can cause various endocrine side effects, especially if not used concurrently with the appropriate treatment. The clinical implications of this adverse event and management strategies are discussed here in this case report to raise awareness about this potential risk in patients with prostate cancer undergoing treatment with abiraterone acetate, especially when used in an erroneous manner without monitoring. Full article

Background and Clinical Significance: Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men worldwide. While bone and lymph nodes are the most frequent metastatic sites, prostate cancer cells have the potential to spread to virtually any organ, including the pleura, which is an exceedingly rare initial site of presentation that can mimic mesothelioma or primary lung cancer. Case Presentation: We describe a 77-year-old man who presented with exertional dyspnea and intermittent cough, initially suggesting a cardiopulmonary etiology. Imaging revealed multiple pleural nodules and an extensive right-sided pleural effusion. Despite a borderline serum prostate-specific antigen (PSA) level of 2.91 ng/mL, histopathology and immunohistochemistry of pleural biopsies confirmed metastatic prostate adenocarcinoma. Subsequent imaging identified a PIRADS 5 lesion in the prostate, and a biopsy confirmed ISUP Grade Group 5 disease (Gleason score 4 + 5 = 9). A bone scan showed no skeletal metastases, and a contrast-enhanced CT of the abdomen found no additional metastatic lesions. The patient was started on androgen deprivation therapy followed by abiraterone. This case underscores the diagnostic challenge posed by atypical metastatic presentations of prostate cancer. Low or moderately elevated PSA can obscure suspicion of prostate origin, especially with pleural-based lesions suggestive of mesothelioma. Immunohistochemical markers, including androgen receptors, AMACR, and Prostein, are critical for accurate diagnosis. Conclusions: Clinicians must maintain a high index of suspicion for prostate cancer in older men with unexplained pleural effusions, nodules, or masses, even with low-normal PSA levels. Early recognition and prompt treatment can improve outcomes, despite the rarity and aggressiveness of pleural metastases. Full article

Radium-223 (²²³Ra) was the first radioactive isotope approved for treating castration-resistant prostate cancer (CRPC) with symptomatic bone metastases without visceral metastatic disease. To better understand the action of ²²³Ra, its role in the tumor microenvironment represents a crucial aspect. A literature search was conducted using the PubMed/MEDLINE database and studies regarding the relationship between ²²³Ra and the tumoral microenvironment were considered. The tumoral microenvironment is a complex setting in which complex interactions between cells and molecules occur. Radium-223, as an alpha-emitter, induces double-stranded DNA breaks; to potentiate this effect, it could be used in patients with genetic instability but also in combination with therapies which inhibit DNA repair, modulate the immune response, or control tumor growth. In conclusion, a few studies have taken into consideration the tumoral microenvironment in association with ²²³Ra. However, its understanding is a priority to better comprehend how to effectively exploit ²²³Ra and its action mechanism. Full article

Background/Objectives: Prostate cancer (PCa) patients who do not respond to androgen deprivation therapy (ADT), referred to as castration-resistant prostate cancer (CRPC), remain a clinical challenge due to confirm the aggressive nature of CRPC and its resistance to conventional therapies. This study aims to investigate the potential of microRNAs (miRNAs) as biomarkers for predicting therapeutic response in CRPC patients. Methods: We performed miRNA and mRNA expression analyses using publicly available datasets and applied 3D cell culture models to replicate more physiologically relevant tumor conditions. Genetic analysis techniques were employed on publicly available data, and expression profiles from 3D cell culture models were examined. Results: Eighteen miRNAs with differential expression were identified between patients who responded favorably to abiraterone therapy (responders) and those with advanced CRPC (non-responders). Specifically, miRNAs such as hsa-miR-152-3p and hsa-miR-34a-3p were found to be associated with critical pathways, including TGF-? signaling and P53, which are linked to therapeutic resistance. Several miRNAs were identified as potential predictors of treatment efficacy, including therapies like abiraterone. Conclusions: These results indicate that miRNAs could serve as non-invasive biomarkers for predicting therapeutic outcomes, facilitating a more personalized approach to CRPC treatment. This study provides a novel perspective on treatment strategies for CRPC, emphasizing the role of miRNAs in improving therapeutic precision and efficacy in this complex disease. Full article

Background/Objectives: Several drugs used to treat prostate cancer have been reported to cause cardiovascular adverse events, and this study sought to identify the real-world risk. Methods: This study utilized real-world data from the FAERS to analyze the association between prostate cancer treatment and cardiovascular adverse events. It evaluated men treated with LHRH agonists and antagonists, antiandrogens, androgen synthesis inhibitors, and PARP inhibitors from 2003 to 2023. This study included patients treated with leuprolide, goserelin, triptorelin, degarelix, relugolix, bicalutamide, flutamide, apalutamide, nilutamide, abiraterone, enzalutamide, olaparib, rucaparib, talazoparib, and niraparib. The main outcome measure was the reported odds ratio (ROR) of adverse cardiovascular event associated with these treatments. Results: Among the 4,049,329 unique adverse event reports, 4391 cardiovascular events were identified. Leuprolide (ROR 0.481, 95% CI: 0.423–0.547), triptorelin (ROR 0.527, 95% CI: 0.305–0.909), enzalutamide (ROR 0.393, 95% CI: 0.341–0.452), and olaparib (ROR 0.145, 95% CI: 0.054–0.386) reduced the risk of myocardial infarction. Goserelin increased the risk of myocardial infarction (ROR 2.235, 95% CI: 1.367–3.654). Degarelix and relugolix both increased the risk of heart failure (ROR 3.136, 95% CI: 2.186–4.497), and enzalutamide was associated with an increased risk of heart failure (ROR 1.305, 95% CI: 1.135–1.501). Bicalutamide increased the risk of unstable angina (ROR 3.019, 95% CI: 1.621–5.622) and heart failure (ROR 3.730, 95% CI: 3.085–4.510). Niraparib increased the risk of hypertension (ROR 4.154, 95% CI: 1.709–10.092). Conclusions: These findings underscore the need for clinicians to monitor cardiac complications in patients undergoing these therapies. Full article

Due to the high prostate cancer incidence worldwide, the development of different methods of treatment continues to be a hot research topic. Since its first clinical application at the beginning of the 2010s, abiraterone in the form of prodrug abiraterone acetate continues to be the most used hormone derivative in the treatment of castration-resistant prostate cancer. This is the reason behind the publication of many scientific results regarding its synthesis, biological activity, metabolism, novel designed steroid derivatives based on its structure, etc. A similar steroid compound with a heterocycle in the C17 position, called galeterone, also designed to treat prostate cancer, continues to be in clinical studies, which provides further proof of the importance of these steroid derivatives. Besides prostate cancer treatment, abiraterone showed indications for possible clinical application in the treatment of breast, ovarian, lung, kidney, salivary gland, and adrenocortical cancer, congenital adrenal hyperplasia, Cushing’s syndrome, and COVID-19, while galeterone is investigated for its use against prostate, pancreatic, and breast cancer. Herein, we report a review comprising methods of synthesis, possible clinical applications, and mechanisms of action, as well as structures and bioactivities of derivatives of these two important steroids. Full article

Recent advances have broadened the range of therapeutic options for mCRPC, with several new treatments, including novel hormonal therapies (enzalutamide, abiraterone), chemotherapeutic agents (docetaxel, cabazitaxel), immunotherapies (sipuleucel-T), and bone targeting radiopharmaceuticals (radium-223) showing improved clinical outcomes and receiving U.S. Food and Drug Administration approval. These new treatments provide new avenues for improving patient survival and quality of life. Radium-223, a targeted alpha-emitter, specifically targets bone metastases, offering palliative benefits and a potential increase in life expectancy. The integration of radium-223 with other treatments shows promise for managing mCRPC. However, the optimal sequencing and combination of radium-223 with other therapies are still being explored, with various clinical trials investigating new therapeutic approaches. The integration of these therapies, especially to provide more effective, personalized treatment strategies, requires further investigation. A thorough literature review was conducted on current treatments for mCRPC, including chemotherapeutic agents, oral hormonal therapies targeting the androgen receptor axis, immunotherapies, and radium-223. Ongoing clinical trials investigating radium-233 in the context of other therapies for the treatment of mCRPC patients were also reviewed. Further studies should focus on determining the optimal sequencing and dosing and identifying biomarkers that predict treatment response to enhance outcomes of mCRPC patients. This review underlines the rational strategies of combining radium-223 with other therapies, investigating their impact on bone in terms of delaying skeletal-related events, and managing bone disease progression in mCRPC patients. Full article

All 189 World Bank member countries are classified by their capita gross national income into one of four income groups. In this review, we aim to explore the economic burden and management of urologic oncology conditions in low- and middle-income countries (LMICs), emphasizing disparities and challenges in treatment access. The current World Bank classification system highlights economic stratification, showing significant health outcome disparities, particularly in urologic oncology conditions including kidney, bladder, and prostate cancer. First, this review focuses on the management of advanced prostate cancer in Asian LMICs, revealing higher mortality-to-incidence ratios and a greater prevalence of metastatic disease compared to high-income countries (HICs). The prohibitive costs of novel hormonal therapies (NHTs) like abiraterone and enzalutamide limit their use and exacerbate outcome disparities. Second, we review Wilms tumor treatment with chemotherapy in African countries, noting significant price variations for adapted and non-adapted regimens across different economic settings. The cost of chemotherapy agents, particularly dactinomycin, acts as a primary driver of treatment expenses, underscoring the economic challenges in providing high-quality care. Lastly, bladder cancer treatment costs in Brazil and Middle Eastern countries are examined, highlighting how detrimental the economic burden of intravesical therapies, like mitomycin C and Bacillus Calmette–Guérin (BCG), is on treatment accessibility. Overall, this literature review emphasizes the financial strain on healthcare systems and patients, particularly in regions facing economic instability and drug shortages, and underscores the need for international cooperation and effective resource allocation to address the economic barriers to urologic care in LMICs, aiming to improve health outcomes and ensure equitable access to advanced treatments. Full article

This study presents the development and validation of environmentally friendly analytical methods for quantifying Abiraterone Acetate (AA) in both its pure form and commercial pharmaceutical formulations. An optimized High-Performance Liquid Chromatography (HPLC) method was developed using an Agilent Extend C18 column (250 mm × 4.6 mm, 5 μm) at 25 °C. The mobile phase consisted of formic acid and ethanol in isocratic mode, with a flow rate of 1.0 mL min⁻¹, and detection was performed at 253 nm. The spectrophotometric method involved a comprehensive evaluation of AA’s spectral properties in various solvents, with ultrapure water providing the most suitable spectra for analysis at 253 nm. Both methods were validated according to ICH guidelines, demonstrating selectivity, linearity, accuracy, precision, detection and quantification limits, and robustness, with correlation coefficients exceeding 0.999 across the 5–30 μg mL⁻¹ concentration range. Comparative statistical analysis using Student’s t-test and Fisher’s F-test showed no significant differences between the two methods. The environmental impact of both methods was assessed using AGREE and GAPI software, confirming their sustainability. These validated methods offer reliable and eco-friendly approaches for the quantitative analysis of AA in tablet formulations, promoting safer and greener laboratory practices in pharmaceutical analysis. Full article

Background/Objectives: Abiraterone acetate, apalutamide, darolutamide, and enzalutamide, which make up the androgen receptor axis-targeted therapies (ARATs) drug class, are commonly used in the management of prostate cancer. Many patients on ARATs also receive oral antithrombotic therapy (i.e., anticoagulants or antiplatelets). The concomitant use of ARATs and antithrombotic therapies creates the potential for clinically relevant drug–drug interactions, but the literature regarding the actual consequences of these interactions, and guidance for co-prescribing, is limited. We assembled a multidisciplinary panel of experts and provided them with clinical information derived from a comprehensive literature review regarding the drug–drug interactions between ARATs and antithrombotic therapies. Methods: A three-stage modified electronic Delphi process was used to gather and consolidate opinions from the panel. Each stage consisted of up to three rounds of voting to achieve consensus on which ARAT/antithrombotic therapy drug pairs warrant attention, the possible clinical consequences of drug–drug interactions, and suggested actions for management. Results: The panel achieved consensus to avoid 11 ARAT/antithrombotic therapy drug pairs and modify therapy for eight pairs. Assessments relied heavily on pharmacokinetic data and extrapolation from drug–drug interaction studies of similarly metabolized drugs. Conclusions: This e-Delphi process highlights the need for further research into the clinical impact of ARAT/antithrombotic drug interactions. Nonetheless, the suggested actions aim to provide clinicians with a practical framework for therapeutic decision making. Full article

Most patients with metastatic prostate cancer eventually develop resistance to primary androgen deprivation therapy. To identify predictive biomarker for Abiraterone acetate/prednisone resistance, we screened alternative splice variants between responders and non-responders from the PROMOTE clinical study and pinned down the most significant variant, CENPK–delta8. Through preclinical patient-derived mouse xenograft (PDX) and 3D organoids obtained from responders and non-responders, as well as in vitro models, aberrant CENPK–delta8 expression was determined to link to drug resistance via enhanced migration and proliferation. The FLNA and FLOT1 were observed to specifically bind to CENK–delta8 rather than wild-type CENPK, underscoring the role of CENPK–delta8 in cytoskeleton organization and cell migration. Our study, leveraging data from the PROMOTE study, TCGA, and TCGA SpliceReq databases, highlights the important function of alternative splice variants in drug response and their potential to be prognostic biomarkers for improving individual therapeutic outcomes in precision medicine. Full article

Objective: Abi, when used in conjunction with prednisone, is an established treatment for advanced PCa. Our goal was to explore the level of autophagy induced by Abi treatment, both alone and in combination with the autophagy inhibitor Chl, in a castrated mouse xenograft model. Methods: LNCaP cells were injected into the left and right sides of the back of nude mice that had been previously castrated. Mice were divided into four groups and treated daily with intraperitoneal injections of vehicle (control), Abi (10 mg/kg), Abi (10 mg/kg) combined with Chl (10 mg/kg), or Chl (10 mg/kg), and were monitored for periods of 2 and 3 weeks. Results: A significant reduction in tumor weight was observed in mice treated with the combination therapy, as opposed to those receiving vehicle control, Abi, or Chl alone. Mice receiving Abi + Chl exhibited reduced expression of ATG5, Beclin 1, and LC3 punctuations, along with an increase in P62, as determined by immunofluorescence and WES analysis. AR expression decreased significantly in all treatment groups compared to the control. PSMA expression was highest in the vehicle and combined treatment groups after 3 weeks, with a significant reduction observed with Chl treatment. Conclusions: These findings demonstrate that Abi + Chl treatment lowers autophagy levels and suppresses tumors more effectively than Abi alone. Full article

Prostate cancer (PC) is one of the most commonly diagnosed tumours among men. Second-generation androgen receptor axis-targeted (ARAT) agents, namely abiraterone acetate (AbA) and enzalutamide (ENZ), are currently used in the management of metastatic castration-resistant PC (mCRPC). However, the treatment is challenging due to the lack of prognostic biomarkers. Meanwhile, single-nucleotide polymorphisms (SNPs) have emerged as potential prognostic indicators of mCRPC. Thus, this study evaluated the impact of relevant SNPs on the treatment outcomes of 123 mCRPC patients enrolled in a hospital-based cohort study. The CYP17A1 rs2486758 C allele was associated with a 50% reduction in the risk of developing castration resistance (hazard ratio (HR) = 0.55; p = 0.003). Among patients without metastasis at tumour diagnosis and under AbA, a marginal association between YBX1 rs10493112 and progression-free survival was detected (log-rank test, p = 0.056). In the same subgroup, significant associations of HSD3B1 rs1047303 (CC/CA vs. AA; HR = 3.41; p = 0.025), YBX1 rs12030724 (AT vs. AA; HR = 3.54; p = 0.039) and YBX1 rs10493112 (log-rank test, p = 0.041; CC vs. AA/AC; HR = 3.22; p = 0.053) with overall survival were also observed, which were confirmed by multivariate Cox analyses. Although validation with larger cohorts is required, these findings suggest that SNPs could enhance the prognosis assessment of mCRPC patients, leading to a more personalised treatment. Full article

Neuroendocrine differentiation (NED) represents a possible androgen receptor pathway inhibitors (ARPI) resistance mechanism in metastatic castration resistance prostate cancer (mCRPC). As mCRPC with NED has been excluded from clinical trials evaluating ARPI efficacy, this study investigates the prognostic impact of NED in mCRPC patients treated with ARPIs. Methods: We retrospectively analyzed 327 mCRPC patient data treated with Enzalutamide or Abiraterone in the first and second or successive lines of treatment. NED was assessed using prostate biopsy samples through immunohistochemical staining. Results: NED was confirmed in 32/327 (9.8%) mCRPC patients. In the overall population, mCRPC with NED showed worse PFS (4.38 vs. 11.48 months HR 2.505 [1.71–3.68] p < 0.05), disease control rate (DCR), and PSA response. In the first line setting, mCRPC with NED demonstrated worse PFS (8.5 vs. 14.9 months HR 2.13 [1.18–3.88], p < 0.05). Similarly, in the second or successive lines, mCRPC with NED showed worse PFS (4.0 vs. 7.5 months HR 2.43 [1.45–4.05] p < 0.05), DCR, PSA response and OS (12.53 vs. 18.03 months HR 1.86 [1.12–3.10] p < 0.05). The adverse impact of NED on PFS was consistence across all subgroups; we also noted a trend of worse PFS in patients with high vs. low NED. Conclusions: In our study, mCRPC with NED treated with Enzalutamide or Abiraterone showed worse clinical outcomes. NED assessment should be considered to optimize treatment decisions in the mCRPC setting. Full article

Given its known prognostic role, we aimed to investigate the role of neutrophil–lymphocyte ratio (NLR) as a biomarker in metastatic castration-resistant prostate cancer (mCRPC) patients receiving ADT, either as monotherapy or in conjunction with abiraterone acetate (AA) and prednisone. This retrospective cohort study analyzed the LATITUDE study of men with high-risk mCSPC. Patients were assigned to receive either AA, prednisone, and androgen deprivation therapy (ADT) or placebo plus ADT. Using a previously established NLR threshold of 2.5, we evaluated if this could predict clinical response to abiraterone. At baseline, there were no significant differences in NLR values between the treatment groups. Of the known baseline prognostic factors, NLR was associated with albumin levels and Eastern Cooperative Oncology Group performance scores. Moreover, the number of bone metastases was higher in patients with NLR ≥ 2.5. On multivariable analysis, baseline NLR ≥ 2.5 did not predict overall survival, PSA progression-free, or metastasis-free survival. However, changes in PSA and NLR at six months indicated distinct survival patterns between the placebo and AA groups, suggesting the potential for their combined assessment as a prognostic tool. Baseline NLR was not an independent predictor factor for response to AA in the LATITUDE study, though NLR changes at 6 months may predict better survival beyond PSA values alone. Further research is required to better understand in which patients with advanced prostate cancer NLR changes may be a useful prognostic tool. Full article