Improving the management of patients with prostate cancer receiving long‐term androgen deprivation therapy

Abstract

3In many patients with prostate cancer, androgen deprivation therapy (ADT) is administered over prolonged periods of time. The benefi ts of long-term ADT in patients with advanced disease are well established and, more recently, studies have shown that long-term adjuvant ADT used in combination with radiotherapy improves survival in patients with earlier stages of disease. Nevertheless, clinicians should remain aware of the potential long-term side effects of ADT and the strategies that can be used to manage or prevent long-term complications.One such strategy is intermittent androgen deprivation (IAD), in which patients receive cycles of ADT, the duration of which is usually determined by PSA levels. Accumulating data indicate that this approach improves the tolerability of ADT (particularly sexual dysfunction) and patients ' quality of life, without compromising clinical outcomes (progression and survival). Indeed, the latest European Association of Urology guidelines state that IAD should no longer be considered investigational. Nevertheless, some questions remain unanswered, including: who are the most suitable patients for IAD and what are the optimal PSA levels for stopping and restarting treatment?Osteoporosis (and the resultant increased risk of fractures) is a well-recognized complication of long-term ADT. Bone mineral density should be measured before and during long-term ADT and patients advised to make appropriate lifestyle changes to help preserve bone health. Pharmacological intervention is also an option. Denosumab (an NF-κ B ligand inhibitor) signifi cantly reduces ADT-induced bone loss and the risk of fractures in patients with non-metastatic disease. In those whose disease has metastasized, zoledronate and denosumab are licensed to prevent skeletal-related events and a large randomized study has shown that denosumab is more effective than zoledronate in this setting. KEYWORDSintermittent androgen deprivation therapy , tolerability , quality of life , bone mineral density , skeletal-related events , denosumab

Metformin anti-tumor effect via disruption of the MID1 translational regulator complex and AR downregulation in prostate cancer cells

“…The standard treatment for advanced prostate cancer is androgen deprivation therapy. It is initially effective in the majority of tumours but its long-term use is associated with side effects such as cardiovascular problems, metabolic disease, diabetes mellitus, and development of therapy resistance [38]. A combination of metformin with androgen deprivation might be a promising combination to improve efficacy and relieve side effects.…”

Androgen deprivation therapy for prostate cancer: long-term safety and patient outcomes

“…Monitoring bone health and bone loss preventive measures are highly recommended in patients on long term ADT as the risk of loss of BMD and bone fracture is directly associated with the length of ADT treatment. Baseline BMD measurement using dual X-ray absorptiometry before starting ADT and regular BMD measurements based on initial T-score, lifestyle modifications such as increased exercise, calcium (1,500 mg) and vitamin D (800 IU) supplementation, smoking cessation, decreased alcohol consumption, and weight loss are among the suggested monitoring and preventive measures 21. Bisphosphonates clearly prevent bone loss and increase BMD in PCa patients on long-term ADT and intravenous zolendronic acid also prevents fractures in men with metastatic and castrate-resistant PCa.…”

“…Denosumab, a human monoclonal antibody against RANK-L, however, has been shown to reduce the risk of vertebral fractures in men receiving ADT for non-metastatic PCa. Denosumab has also been shown to be superior to zoledronic acid in preventing skeletal-related events in patients with metastatic or castrate-resistant PCa 21. However, neither of these drugs have been shown to prevent bone metastasis in non-metastatic PCa 22.…”

Evaluation of Prostate Cancer with 11C-Choline PET/CT for Treatment Planning, Response Assessment, and Prognosis

“…Nevertheless, ADT causes incontrovertible side effects. Furthermore, patients with hormonal blockade sooner or later will progress to a CRPC condition (32). Recently, Berkovic et al (33) investigated whether repeated stereotactic body radiotherapy of oligometastatic disease could defer the initiation of ADT in patients with low-volume metastases.…”

“…Patients with PCa may develop resistance to ADT during BCR, and consequently, the hormonal blockade loses its protective effect on tumor cell growth (32). The condition of CRPC, particularly in the presence of proven metastatic spread (mCRPC), is associated with a median overall survival of 2-3 y (42).…”