Contemporary Role of Androgen Deprivation Therapy for Prostate Cancer

Abstract

Context Androgen deprivation therapy (ADT) for prostate cancer (PCa) represents one of the most effective systemic palliative treatments known for solid tumors. Although clinical trials have assessed the role of ADT in patients with metastatic and advanced locoregional disease, the risk–benefit ratio, especially in earlier stages, remains poorly defined. Given the mounting evidence for potentially life-threatening adverse effects with short- and long-term ADT, it is important to redefine the role of ADT for this disease. Objective Review the published experience with currently available ADT approaches in various contemporary clinical settings of PCa and reported serious treatment-related adverse events. This review addresses the level of evidence associated with the use of ADT in PCa, focusing upon survival outcome measures. Furthermore, this paper discusses evolving approaches targeting androgen receptor signaling pathways and emerging evidence from clinical trials with newer compounds. Evidence acquisition A comprehensive review of the literature was performed, focusing on data from the last 10 yr (January 2000 to July 2011) and using the terms androgen deprivation, hormone treatment, prostate cancer and adverse effects. Abstracts from trials reported at international conferences held in 2010 and 2011 were also evaluated. Evidence synthesis Data from randomized controlled trials and population-based studies were analyzed in different clinical paradigms. Specifically, the role of ADT was evaluated in patients with nonmetastatic disease as the primary and sole treatment, in combination with radiation therapy (RT) or after surgery, and in patients with metastatic disease. The data suggest that in men with nonmetastatic disease, the use of primary ADT as monotherapy has not shown a benefit and is not recommended, while ADT combined with conventional-dose RT (<72 Gy) for patients with high-risk disease may delay progression and prolong survival. The postoperative use of ADT remains poorly evaluated in prospective studies. Likewise, there are no trials evaluating the role of ADT in patients with biochemical relapses after surgery or RT. In patients with metastatic disease, there is a clear benefit in terms of quality of life, reduction of disease-associated morbidity, and possibly survival. Treatment with bilateral orchiectomy, luteinizing hormone–releasing hormone agonist therapy, with and without antiandrogens has been associated with various serious adverse events, including cardiovascular disease, diabetes, and skeletal complications that may also affect mortality. Conclusions Although ADT is an effective treatment of PCa, consistent long-term benefits in terms of quality and quantity of life are predominantly evident in patients with advanced/metastatic disease or when ADT is used in combination with RT (<72 Gy) in patients with high-risk tumors. Implementation of ADT should be evidence based, with special consideration to adverse events and the risk–benefit ratio.

Clinical presentation and predictors of survival related to extent of bone metastasis in 900 prostate cancer patients

“…Although the introduction of PSA as a diagnostic tool at the end of the last century has led to a marked stage migration of the disease with an increasing proportion of prostate cancer cases being diagnosed at a clinically localised stage, many men still have distant metastases at diagnosis (12% in Sweden in 2014) [1]. Once the tumour has metastasised the disease is practically incurable, albeit many men live for several years with generalised prostate cancer [2,3].…”

Clinical Assessment of Taxanes in the First-Line Cytotoxic Therapy of Castration-Resistant Prostate Cancer

“…Несмотря на значительное увеличение числа больных с ранними формами заболевания, 45,5% пациентов на период выявления заболевания имеют местно-распро-страненные и метастатические формы [2].…”

The current abilities of third-generation luteinizing hormone-releasing hormone antagonists in the treatment of hormone-responsive prostate cancer

“…АДТ является стандартом лечения распространенных форм РПЖ, а также может быть использована в качестве неоадъ-ювантной терапии при планировании радикального лечения у определенных групп больных [1,2]. РПЖ -это наиболее распространенная злокачественная опухоль у пожилых мужчин в Европе.…”