0
selected
-
1.
Bone health effects of androgen-deprivation therapy and androgen receptor inhibitors in patients with nonmetastatic castration-resistant prostate cancer.
Hussain, A, Tripathi, A, Pieczonka, C, Cope, D, McNatty, A, Logothetis, C, Guise, T
Prostate cancer and prostatic diseases. 2021;(2):290-300
-
-
Free full text
-
Abstract
BACKGROUND Osteoporosis is a skeletal disorder characterized by compromised bone strength, resulting in increased fracture risk. Patients with prostate cancer may have multiple risk factors contributing to bone fragility: advanced age, hypogonadism, and long-term use of androgen-deprivation therapy. Despite absence of metastatic disease, patients with nonmetastatic castrate-resistant prostate cancer receiving newer androgen receptor inhibitors can experience decreased bone mineral density. A systematic approach to bone health care has been hampered by a simplistic view that does not account for heterogeneity among prostate cancer patients or treatments they receive. This review aims to raise awareness in oncology and urology communities regarding the complexity of bone health, and to provide a framework for management strategies for patients with nonmetastatic castrate-resistant prostate cancer receiving androgen receptor inhibitor treatment. METHODS We searched peer-reviewed literature on the PubMed database using key words "androgen-deprivation therapy," "androgen receptor inhibitors," "bone," "bone complications," and "nonmetastatic prostate cancer" from 2000 to present. RESULTS We discuss how androgen inhibition affects bone health in patients with nonmetastatic castrate-resistant prostate cancer. We present data from phase 3 trials on the three approved androgen receptor inhibitors with regard to effects on bone. Finally, we present management strategies for maintenance of bone health. CONCLUSIONS In patients with nonmetastatic castrate-resistant prostate cancer, aging, and antiandrogen therapy contribute to bone fragility. Newer androgen receptor inhibitors were associated with falls or fractures in a small subset of patients. Management guidelines include regular assessment of bone density, nutritional guidance, and use of antiresorptive bone health agents when warranted.
-
2.
The role of adrenal derived androgens in castration resistant prostate cancer.
Barnard, M, Mostaghel, EA, Auchus, RJ, Storbeck, KH
The Journal of steroid biochemistry and molecular biology. 2020;:105506
-
-
Free full text
-
Abstract
Castration resistant prostate cancer (CRPC) remains androgen dependant despite castrate levels of circulating testosterone following androgen deprivation therapy, the first line of treatment for advanced metstatic prostate cancer. CRPC is characterized by alterations in the expression levels of steroidgenic enzymes that enable the tumour to derive potent androgens from circulating adrenal androgen precursors. Intratumoral androgen biosynthesis leads to the localized production of both canonical androgens such as 5α-dihydrotestosterone (DHT) as well as less well characterized 11-oxygenated androgens, which until recently have been overlooked in the context of CRPC. In this review we discuss the contribution of both canonical and 11-oxygenated androgen precursors to the intratumoral androgen pool in CRPC. We present evidence that CRPC remains androgen dependent and discuss the alterations in steroidogenic enzyme expression and how these affect the various pathways to intratumoral androgen biosynthesis. Finally we summarize the current treatment strategies for targeting adrenal derived androgen biosynthesis.
-
3.
Germline HSD3B1 Genetics and Prostate Cancer Outcomes.
Thomas, L, Sharifi, N
Urology. 2020;:13-21
-
-
Free full text
-
Abstract
Dihydrotestosterone synthesis in prostate cancer from adrenal DHEA/DHEA-sulfate requires enzymatic conversion in tumor tissues. 3β-hydroxysteroid dehydrogenase-1 is an absolutely necessary enzyme for such dihydrotestosterone synthesis and is encoded by the gene HSD3B1 which comes in 2 functional inherited forms described in 2013. The adrenal-permissive HSD3B1(1245C) allele allows for rapid dihydrotestosterone synthesis. The adrenal-restrictive HSD3B1(1245A) allele limits androgen synthesis. Studies from multiple cohorts show that adrenal-permissive allele inheritance confers worse outcomes and shorter survival after castration in low-volume prostate cancer and poor outcomes after abiraterone or enzalutamide treatment for castration-resistant prostate cancer. Here, we review the clinical data and implications.
-
4.
Nutrition care guidelines for men with prostate cancer undergoing androgen deprivation therapy: do we have enough evidence?
Barnes, KA, Ball, LE, Galvão, DA, Newton, RU, Chambers, SK
Prostate cancer and prostatic diseases. 2019;(2):221-234
Abstract
BACKGROUND To review the evidence available to support clinical practice guidelines for dietary interventions aimed at mitigating the side effects of androgen deprivation therapy (ADT) in men with prostate cancer, and to identify future research priorities. METHODS An analytical model was designed to select and interpret evidence for the effect of dietary interventions on ADT side effects. Key terms identified articles that investigated dietary interventions to mitigate ADT side effects among men treated for prostate cancer. Medline, Embase, Proquest, CINAHL, Cochrane databases, and PubMed were searched from inception through June, 2018. Clinical trial registries were also searched for up-to-date study protocols. Articles were not restricted on design. Methodological quality was assessed using the mixed methods appraisal tool. RESULTS Sixteen articles met inclusion criteria, each with distinct dietary interventions. Twelve studies used interventions that combined diet with physical activity and/or medication and/or counselling. Four articles examined the effect of diet alone on ADT side effects. Of those, three articles measured changes to participants' dietary intake and influence on ADT side effects. One article showed daily caffeinated beverages improved cancer-related fatigue. Two articles showed no impact of isoflavone supplementation on hot flushes, quality of life, body mass index, or blood lipids. Dietary intake and compliance was poorly reported across all studies limiting knowledge of acceptability and feasibility for dietary interventions. Information on the nutrition care practices and views of clinicians treating men for prostate cancer is limited. No articles measured the impact of diet on long-term ADT side effects. Methodological quality of included papers ranged from weak to strong. CONCLUSIONS Current evidence for dietary interventions to mitigate ADT side effects is limited. Further investigations are warranted to explore the impact of changes in dietary intake on ADT side effects before practice guidelines can be considered.
-
5.
HSD3B1 status as a biomarker of androgen deprivation resistance and implications for prostate cancer.
Hettel, D, Sharifi, N
Nature reviews. Urology. 2018;(3):191-196
Abstract
Patients with advanced prostate cancer who receive androgen deprivation therapy (ADT) almost invariably develop castration-resistant disease. The mechanism of resistance is largely based on synthesis of intratumoral androgens from adrenal precursors, requiring enzymatic action of 3β-hydroxysteroid dehydrogenase/Δ5→4 isomerase 1 (3β-HSD1), encoded by HSD3B1. A nucleotide polymorphism (1245A>C) in HSD3B1 results in a protein variant with increased steady-state levels and subsequently increased androgen synthesis from extragonadal precursors. Multiple clinical studies have shown that patients with the variant allele have significantly worse outcomes after ADT than those without, indicating that HSD3B1 variant status is a predictive biomarker of shortened ADT response. In addition, inheritance of the HSD3B1 variant is associated with extended responses to 17α-hydroxylase/17,20-lyase (CYP17A1) inhibition with a nonsteroidal agent, adding to evidence of increased tumour dependence on extragonadal androgens in patients who inherited the HSD3B1 variant. However, steroidal drugs with a 3β-hydroxyl, Δ5-structure, such as abiraterone, are also metabolized by 3β-HSD1, and 5α-abiraterone, a downstream metabolite, has been shown to activate the androgen receptor, potentially driving cancer progression. These data indicate a potential requirement to modify the treatment framework of patients harbouring variant HSD3B1.
-
6.
[Metabolic complications of androgen deprivation therapy and its intervention management].
Hu, YH, Wu, S, Zhang, M
Zhonghua nan ke xue = National journal of andrology. 2018;(3):277-281
Abstract
Androgen deprivation therapy (ADT) is one of the dominant treatment options for advanced prostate cancer, which has been certified to significantly improve the overall survival of prostate cancer patients. However, it sometimes can also produce severe adverse effects on body metabolism. This review summarizes the adverse effects of ADT on body composition, the levels of cholesterol and blood glucose, and the cardiovascular system, and the intervention management of these metabolic complications as well.
-
7.
Pharmacological interventions for the prevention of insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults.
van den Blink, QU, Garcez, K, Henson, CC, Davidson, SE, Higham, CE
The Cochrane database of systematic reviews. 2018;(4):CD010604
-
-
Free full text
-
Abstract
BACKGROUND Pelvic radiotherapy is a treatment delivered to an estimated 150,000 to 300,000 people annually across high-income countries. Fractures due to normal stresses on weakened bone due to radiotherapy are termed insufficiency fractures. Pelvic radiotherapy-related interruption of the blood supply to the hip is termed avascular necrosis and is another recognised complication. The reported incidences of insufficiency fractures are 2.7% to 89% and risk of developing avascular necrosis is 0.5%. These complications lead to significant morbidity in terms of pain, immobility and consequently risk of infections, pressure sores and mortality. OBJECTIVES To assess the effects of pharmacological interventions for preventing insufficiency fractures and avascular necrosis in adults over 18 years of age undergoing pelvic radiotherapy. SEARCH METHODS We performed electronic literature searches in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and DARE to 19 April 2017. We also searched trial registries. Further relevant studies were identified through handsearching of citation lists of included studies. SELECTION CRITERIA Randomised controlled trials (RCTs) or non RCTs with concurrent comparison groups including quasi-RCTs, cluster RCTs, prospective cohort studies and case series of 30 or more participants were screened. We included studies assessing the effect of pharmacological interventions in adults over 18 years of age undergoing radical pelvic radiotherapy as part of anticancer treatment for a primary pelvic malignancy. We excluded studies involving radiotherapy for bone metastases. We assessed use of pharmacological interventions at any stage before or during pelvic radiotherapy. Interventions included calcium or vitamin D (or both) supplementation, bisphosphonates, selective oestrogen receptor modulators, hormone replacement therapy (oestrogen or testosterone), denosumab and calcitonin. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. We contacted study authors to obtain missing data. Data were to be pooled using the random-effects model if study comparisons were similar, otherwise results were to be reported narratively. MAIN RESULTS We included two RCTs (1167 participants). The first RCT compared zoledronic acid with placebo in 96 men undergoing pelvic radiotherapy for non-metastatic prostate cancer.The second RCT had four treatment arms, two of which evaluated zoledronic acid plus adjuvant androgen suppression compared with androgen suppression only in 1071 men undergoing pelvic radiotherapy for non-metastatic prostate cancer.Both studies were at a moderate to high risk of bias and all evidence was judged to be of very low certainty.The studies provided no evidence on the primary outcomes of the review and provided limited data in relation to secondary outcomes, such that meta-analyses were not possible. Both studies focused on interventions to improve bone health in relation to androgen deprivation rather than radiation-related insufficiency fractures and avascular necrosis. Few fractures were described in each study and those described were not specific to insufficiency fractures secondary to radiotherapy. Both studies reported that zoledronic acid in addition to androgen deprivation and pelvic radiotherapy led to improvements in BMD; however, the changes in BMD were measured and reported differently. There was no available evidence regarding adverse effects. AUTHORS' CONCLUSIONS The evidence relating to interventions to prevent insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults is of very low certainty. This review highlights the need for prospective clinical trials using interventions prior to and during radiotherapy to prevent radiation-related bone morbidity, insufficiency fractures and avascular necrosis. Future trials could involve prospective assessment of bone health including BMD and bone turnover markers prior to pelvic radiotherapy. The interventions for investigation could begin as radiotherapy commences and remain ongoing for 12 to 24 months. Bone turnover markers and BMD could be used as surrogate markers for bone health in addition to radiographic imaging to report on presence of insufficiency fractures and development of avascular necrosis. Clinical assessments and patient reported outcomes would help to identify any associated adverse effects of treatment and quality of life outcomes.
-
8.
Metabolic changes in patients with prostate cancer during androgen deprivation therapy.
Mitsuzuka, K, Arai, Y
International journal of urology : official journal of the Japanese Urological Association. 2018;(1):45-53
Abstract
Androgen deprivation therapy continues to be widely used for the treatment of prostate cancer despite the appearance of new-generation androgen-receptor targeting drugs after 2000. Androgen deprivation therapy can alleviate symptoms in patients with metastatic prostate cancer and might have a survival benefit in some patients, but it causes undesirable changes in lipid, glucose, muscle or bone metabolism. These metabolic changes could lead to new onset or worsening of diseases, such as obesity, metabolic syndrome, diabetes mellitus, cardiovascular disease, sarcopenia or fracture. Several studies examining the influence of androgen deprivation therapy in Japanese patients with prostate cancer also showed that metabolic changes, such as weight gain, dyslipidemia or fat accumulation, can occur as in patients in Western countries. Efforts to decrease these unfavorable changes and events are important. First, overuse of androgen deprivation therapy for localized or elderly prostate cancer patients should be reconsidered. Second, intermittent androgen deprivation therapy might be beneficial for selected patients who suffer from impaired quality of life as a result of continuous androgen deprivation therapy. Third, education and instruction, such as diet or exercise, to decrease metabolic changes before initiating androgen deprivation therapy is important, because metabolic changes are likely to occur in the early androgen deprivation therapy period. Fourth, routine monitoring of weight, laboratory data or bone mineral density during androgen deprivation therapy are required to avoid unfavorable events.
-
9.
[Endocrine therapy for prostate cancer.].
Nagaya, N, Horie, S
Clinical calcium. 2018;(11):1527-1533
Abstract
Endocrine therapy for prostate cancer is androgen deprivation therapy and antiandrogens, which are the standard treatment for advanced prostate cancer. Endocrine therapy is effective in most prostate cancers, but as treatment continues, most patients eventually experience resistant to endocrine therapy and disease progression. Patients in this state are said to have castration-resistant prostate cancer. This review outlines the types of endocrine therapy for prostate cancer, the physiological mechanisms of endocrine therapy, its clinical use in Japan and the United States and Europe, new endocrine therapy for castration-resistant prostate cancer, and the side effects to be noted in endocrine therapy.
-
10.
Optic neuritis secondary to antiandrogen therapy.
Ní Mhéalóid, Á, Cunniffe, G
Irish journal of medical science. 2017;(3):565-570
Abstract
BACKGROUND Optic neuropathy is a disorder characterised by dysfunction or destruction of the optic nerve tissues. Acquired causes include interruption in the blood supply, nutritional deficiency, compression by a tumour or aneurysm, trauma, and toxic types (Ambizas and Patel In US Pharm 36(4):HS2-HS6, 1). Drug-induced optic neuropathy is of the toxic type and can be defined as a clinical syndrome characterised by papillomacular bundle damage, central, or cecocentral scotoma, and reduced colour vision (Ambizas and Patel In US Pharm 36(4):HS2-HS6, 2011; Sharma and Sharma In Indian J Ophthalmol 59(2):137-141, 2). AIM: To report a case unilateral optic neuritis, secondary to the use of the antiandrogen, cyproterone acetate. CASE REPORT A 21-year-old female presented with a 4-day history of right brow pain exacerbated by eye movement, and blurring of the right temporal field of vision. She had been taking desogestrel 75 mg and cyproterone acetate 50 mg for the previous 2 months for hormone imbalance. Unaided right visual acuity measured 6/9 and unaided left visual acuity measured 6/6 on Snellen chart. Right red desaturation was present. Goldmann perimetry showed a right enlarged blind spot with predominantly temporal visual field loss. Visually evoked potential (VEP) testing of the right eye showed slightly increased latency, but normal amplitude. Three weeks after discontinuation of the antiandrogen therapy, her symptoms resolved. Repeat Goldmann visual fields showed expansion. CONCLUSION Known side-effects of cyproterone acetate include retinal vascular disorder and retinal vein thrombosis, but an association with optic neuritis had not been described to date. There was a temporal relationship between cessation of the medication and improvement in visual symptoms. This implies that discontinuation of the offending drug constitutes the basis of treatment in drug-induced optic neuropathy.