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Androgen receptor antagonistsView Articles

Volume 23, Number 3Prostate Cancer

Darolutamide for the Management of Metastatic Hormone-Sensitive Prostate Cancer: A Urologist-Oncologist Perspective

Paul DatoRana R. McKay

Metastatic prostate cancer accounts for 8% of all prostate cancer cases in the United States and has an estimated 5-year survival rate of 34%. Androgen-deprivation therapy (ADT) is the cornerstone of treatment for men with metastatic hormone-sensitive prostate cancer (HSPC), but there has been a recent focus on early treatment intensification through dual- or triple-therapy approaches, which have shown substantial survival benefit compared with ADT alone. Darolutamide, a distinct androgen receptor inhibitor, is the latest treatment for men with metastatic HSPC. In the Darolutamide in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer (ARASENS) trial (ClinicalTrials.gov identifier NCT02799602), darolutamide in combination with ADT and docetaxel reduced the risk of death by 32.5% (P < .001) compared with ADT plus docetaxel in men with metastatic HSPC. The most recent National Comprehensive Cancer Network guidelines (2023) support the use of triple-therapy regimens for men with high-volume metastatic HSPC, but concerns about the side effects of the short-term chemotherapy component of this regimen necessitate a comprehensive approach to providing supportive care to ensure that patients are willing to begin and remain on treatment. Effective management should involve a well-informed multidisciplinary team with patient education and support to ensure optimal treatment outcomes. Here, we review the results of the ARASENS trial and consider the implications for the management of metastatic HSPC. By showing a statistically significant reduction in risk of death, triple therapy combining darolutamide with ADT and docetaxel has emerged as a new treatment modality that may help men with metastatic HSPC achieve prolonged survival while maintaining an acceptable quality of life.

Prostatic neoplasmsDrug therapyNeoplasm metastasisAndrogen receptor antagonists

AnejaculationView Articles

Volume 8, Supplement 4Review Articles

Current Concepts in Ejaculatory Dysfunction

Advances in Alpha-Blocker Therapy in the Management of Urological Disorders

Wayne JG HellstromJeffrey P Wolters

Although erectile dysfunction has recently become the most well-known aspect of male sexual dysfunction, the most prevalent male sexual disorders are ejaculatory dysfunctions. Ejaculatory disorders are divided into 4 categories: premature ejaculation (PE), delayed ejaculation, retrograde ejaculation, and anejaculation/anorgasmia. Pharmacologic treatment for certain ejaculatory disorders exists, for example the off-label use of selective serotonin reuptake inhibitors for PE. Unfortunately, the other ejaculatory disorders are less studied and not as well understood. This review revisits the physiology of the normal ejaculatory response, specifically explores the mechanisms of anejaculation, and presents emerging data. The neurophysiology of the ejaculatory reflex is complex, making classification of the role of individual neurotransmitters extremely difficult. However, recent research has elucidated more about the role of serotonin and dopamine at the central level in the physiology of both arousal and orgasm. Other recent studies that look at differing pharmacokinetic profiles and binding affinities of the 1-antagonists serve as an indication of the centrally mediated role of ejaculation and orgasm. As our understanding of the interaction between central and peripheral modulations and regulation of the process of ejaculation increases, the probability of developing centrally acting pharmaceutical agents for the treatment of sexual dysfunction approaches reality. [Rev Urol. 2006;8(suppl 4):S18-S25]

TamsulosinAlfuzosinRetrograde ejaculationAnejaculationEjaculatory disorders

Antiangiogenic therapyView Articles

Volume 9, Supplement 1Review Articles

Current Standard and Investigational Approaches to the Management of Hormone-Refractory Prostate Cancer

New Directions in the Management of Advanced Prostate Cancer

Andrew J ArmstrongDaniel J GeorgePrateek Mendiratta

Prostate cancer is a common cause of death in men and remains incurable in the metastatic setting. In 2004, 2 landmark trials using docetaxel-based chemotherapy, TAX 327 and SWOG 99-16, showed a survival benefit for the first time in metastatic, hormone-refractory prostate cancer. Current research suggests that several distinct mechanisms of androgen-refractory disease may converge in patients with disease progression on androgen deprivation therapy. These findings have identified several potential targets for therapeutic intervention. Current standard and investigational treatment options for this disease are discussed, including chemotherapy and rapidly evolving therapies in phase II/III trials involving antiangiogenic therapies, signal transduction inhibitors, immunomodulatory agents, and nuclear receptor targets. In light of a growing array of treatment options and an increasingly chronic natural history, this review supports a multidisciplinary care approach to these patients, including medical oncologists, urologists, and radiation oncologists, to optimize survival and quality of life. [Rev Urol. 2007;9(suppl 1):S9-S19]

ChemotherapyZoledronic acidHormone-refractory prostate cancerAntiangiogenic therapySignal transduction inhibitorsImmunomodulatory agents