The effect of androgen deprivation therapy on body composition in men with prostate cancer: Systematic review and meta-analysis

Introduction  

The use of androgen deprivation therapy (ADT) in the treatment of prostate cancer is associated with changes in body composition including increased fat and decreased lean mass. Limited information exists regarding the rate and extent of these changes. This systematic review was conducted to determine the effects of ADT on body composition in prostate cancer patients.     

Resistance exercise in men receiving androgen deprivation therapy for prostate cancer.

PURPOSE: Androgen deprivation therapy is a common treatment in men with prostate cancer that may cause fatigue, functional decline, increased body fatness, and loss of lean body tissue. These physical changes can negatively affect health-related quality of life. Resistance exercise may help to counter some of these side effects by reducing fatigue, elevating mood, building muscle mass, and reducing body fat. METHODS: In a two-site study, 155 men with prostate cancer who were scheduled to receive androgen deprivation therapy for at least 3 months after recruitment were randomly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks (82 men) or to a waiting list control group (73 men). The primary outcomes were fatigue and disease-specific quality of life as assessed by self-reported questionnaires after 12 weeks. Secondary outcomes were muscular fitness and body composition. RESULTS: Men assigned to resistance exercise had less interference from fatigue on activities of daily living (P =.002) and higher quality of life (P =.001) than men in the control group. Men in the intervention group demonstrated higher levels of upper body (P =.009) and lower body (P <.001) muscular fitness than men in the control group. The 12-week resistance exercise intervention did not improve body composition as measured by changes in body weight, body mass index, waist circumference, or subcutaneous skinfolds. CONCLUSION: Resistance exercise reduces fatigue and improves quality of life and muscular fitness in men with prostate cancer receiving androgen deprivation therapy. This form of exercise can be an important component of supportive care for these patients.     

Complications of androgen deprivation therapy in men with prostate cancer

Androgen deprivation therapy (ADT) is indicated for the treatment of metastatic prostate cancer and locally advanced disease. In addition to sexual side effects, long-term ADT results in several other changes, including hot flashes; gynecomastia; changes in body composition, metabolism, and the cardiovascular system; osteoporosis; anemia; psychiatric and cognitive problems; and fatigue and diminished quality of life. This review discusses these complications of ADT and treatments aimed at reducing them. It is important for clinicians to anticipate these effects and to initiate measures to prevent or minimize them in order to maintain quality of life in prostate cancer survivors.     

Impact of androgen deprivation therapy on depressive symptoms in men with nonmetastatic prostate cancer

BACKGROUND:

Up to 50% of prostate cancer (PC) patients receive androgen deprivation therapy (ADT), often for several years. Although depression has been reported after a diagnosis of PC, whether ADT leads to or worsens depression is not clear.

METHODS:

Three groups were assembled: ADT users (men initiating continuous ADT), PC controls (PC patients who were not on ADT), and healthy controls. All 3 cohorts were matched on age, education, and physical function, and none had metastases. Depression was measured at study entry and again at 3, 6, and 12 months using the 15‐item Geriatric Depression Scale (GDS). Our primary outcomes were worsening depressive symptoms and incident depression (defined as a GDS score ≥5), analyzed using adjusted linear regression and logistic regression, respectively.

RESULTS:

Of the 257 participants (mean age, 69.1 years), baseline characteristics including GDS score and prior depression were similar across cohorts. In adjusted analyses of initially nondepressed patients, ADT use was not a significant predictor of change in GDS score at 3 months (P = .42), 6 months (P = .25), or 12 months (P = 0.19). Among ADT users, 8%‐9% of participants developed incident depression compared with 0%‐4% among PC controls and 4%‐6% among healthy controls over 3‐12 months (P>.05 at all time points). In a separate analysis of patients with depression at baseline, there was no effect of ADT on depressive symptoms at 3, 6, or 12 months (P = .11, .74, and .12, respectively).

CONCLUSION:

Twelve months of ADT use were not associated with worsening depressive symptoms among nondepressed or depressed patients with nonmetastatic PC. Cancer 2012;. © 2011 American Cancer Society.     

Clinically relevant fatigue in men with hormone-sensitive prostate cancer on long-term androgen deprivation therapy

BackgroundThe purpose of the study was to determine the prevalence and associations of clinically relevant fatigue (CRF) in men with biochemically controlled prostate cancer on long-term androgen deprivation therapy (ADT).Patients and methodsOne hundred and ninety-eight men were surveyed and the prevalence of CRF (Brief Fatigue Inventory score >3) determined. Associations with other measures (Hospital Anxiety and Depression Scale; International Prostate Symptom Score; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; Brief Pain Inventory worst pain; clinical and demographic information) were explored in univariate and multivariate analyses.ResultsEight-one per cent (160 of 198) of questionnaires were analysable. CRF prevalence was 43% (68 of 160). CRF associations included moderate/severe urinary symptoms, anxiety and medical co-morbidities; the strongest associations were depression [odds ratio (OR) 9.8, 95% confidence interval (CI) 4.3–22.8] and pain (OR 9.2, 95% CI 4.0–21.5). After controlling for other factors, the independent associations were depression (OR 4.7, 95% CI 1.6–14.0) and pain (OR 3.1, 95% CI 1.0–8.9). There was no association with age, disease burden or treatment duration.ConclusionsTwo-fifths of men with biochemically controlled prostate cancer on long-term ADT report CRF that interferes with function. Management aimed at improving CRF should address depression and pain.     

Efficacy of walking exercise in promoting cognitive-psychosocial functions in men with prostate cancer receiving androgen deprivation therapy

ABSTRACT: BACKGROUND: Prostate cancer is the most commonly diagnosed non-melanoma cancer among men. Androgen deprivation therapy (ADT) has been the core therapy for men with advanced prostate cancer. It is only in recent years that clinicians began to recognize the cognitive-psychosocial side effects from ADT, which significantly compromise the quality of life of prostate cancer survivors. The objectives of the study are to determine the efficacy of a simple and accessible home-based, walking exercise program in promoting cognitive and psychosocial functions of men with prostate cancer receiving ADT. METHOD: S A 6-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Twenty men with prostate cancer starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 6-month home-based, walking exercise program, while the Control Group will receive standard medical advice from the attending physician. The primary outcomes will be psychosocial and cognitive functions. Cognitive functions including memory, attention, working memory, and executive function will be assessed using a battery of neurocognitive tests at baseline and 6 months. Psychosocial functions including depression, anxiety and self-esteem will be assessed at baseline, 3 and 6 months using the Center for Epidemiological Studies Depression Scale, Spielberger State-Trait Anxiety Inventory, and Rosenberg Self-Esteem Scale. DISCUSSION The significance of the cognitive-psychosocial side effects of ADT in men with prostate cancer has only been recently recognized, and the management remains unclear. This study addresses this issue by designing a simple and accessible home-based, exercise program that may potentially have significant impact on reducing the cognitive and psychosocial side effects of ADT, and ultimately improving the health-related quality of life in men with prostate cancer receiving ADT.     

Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis

BackgroundThere is a need to synthesise the results of numerous randomised controlled trials evaluating the addition of therapies to androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer (mHSPC). This systematic review aims to assess the effects of adding abiraterone acetate plus prednisone/prednisolone (AAP) to ADT.MethodsUsing our framework for adaptive meta-analysis (FAME), we started the review process before trials had been reported and worked collaboratively with trial investigators to anticipate when eligible trial results would emerge. Thus, we could determine the earliest opportunity for reliable meta-analysis and take account of unavailable trials in interpreting results. We searched multiple sources for trials comparing AAP plus ADT versus ADT in men with mHSPC. We obtained results for the primary outcome of overall survival (OS), secondary outcomes of clinical/radiological progression-free survival (PFS) and grade III–IV and grade V toxicity direct from trial teams. Hazard ratios (HRs) for the effects of AAP plus ADT on OS and PFS, Peto Odds Ratios (Peto ORs) for the effects on acute toxicity and interaction HRs for the effects on OS by patient subgroups were combined across trials using fixed-effect meta-analysis.FindingsWe identified three eligible trials, one of which was still recruiting (PEACE-1 (NCT01957436)). Results from the two remaining trials (LATITUDE (NCT01715285) and STAMPEDE (NCT00268476)), representing 82% of all men randomised to AAP plus ADT versus ADT (without docetaxel in either arm), showed a highly significant 38% reduction in the risk of death with AAP plus ADT (HR = 0.62, 95% confidence interval [CI] = 0.53–0.71, p = 0.55 × 10⁻¹⁰), that translates into a 14% absolute improvement in 3-year OS. Despite differences in PFS definitions across trials, we also observed a consistent and highly significant 55% reduction in the risk of clinical/radiological PFS (HR = 0.45, 95% CI = 0.40–0.51, p = 0.66 × 10⁻³⁶) with the addition of AAP, that translates to a 28% absolute improvement at 3 years. There was no evidence of a difference in the OS benefit by Gleason sum score, performance status or nodal status, but the size of the benefit may vary by age. There were more grade III–IV acute cardiac, vascular and hepatic toxicities with AAP plus ADT but no excess of other toxicities or death.InterpretationAdding AAP to ADT is a clinically effective treatment option for men with mHSPC, offering an alternative to docetaxel for men who are starting treatment for the first time. Future research will need to address which of these two agents or whether their combination is most effective, and for whom.     

Bone mineral density in Jamaican men on androgen deprivation therapy for prostate cancer

Background

Androgen deprivation therapy (ADT) has been reported to reduce the bone mineral density (BMD) in men with prostate cancer (CaP). However, Afro-Caribbeans are under-represented in most studies. The aim was to determine the effect of androgen deprivation therapy (ADT) on the bone mineral density (BMD) of men with prostate cancer in Jamaica.

Methods

The study consisted of 346 Jamaican men, over 40 years of age: 133 ADT treated CaP cases (group 1), 43 hormone-naïve CaP controls (group 2) and 170 hormone naïve controls without CaP (group 3). Exclusion criteria included metastatic disease, bisphosphonate therapy or metabolic disease affecting BMD. BMD was measured with a calcaneal ultrasound and expressed in S.D. units relative to young adult men (T score), according to the World Health Organization definition. Patient weight, height and BMI were assessed.

Results

Mean ± sd, age of patients in group 1 (75± 7.4 yrs) was significantly greater than groups 2 and 3 (67 ± 8.1 yrs; 65±12.0 yrs). There was no significant difference in weight and BMI between the 3 groups. . The types of ADT (% of cases, median duration in months with IQR) included LHRH (Luteinizing hormone releasing hormone) analogues (28.6%, 17.9, IQR 20.4), oestrogens (9.8%, 60.5, IQR 45.6) anti-androgens (11.3%, 3.3, IQR 15.2) and orchiectomy (15.7%, 43.4, IQR 63.9). Unadjusted t score of group 1, mean ± sd, (-1.6± 1.5) was significantly less than group 2 (-0.9±1.1) and group 3 (-0.7±1.4), p <0.001. Ninety three (69.9%), 20 (45%) and 75 (42%) of patients in groups 1, 2 and 3 respectively were classified as either osteopenic or osteoporotic (p<0.001). Adjusting for age, there was a significant difference in t scores between groups 1 and 2 as well as between groups 1 and 3 (p<0.001). Compared with oestrogen therapy and adjusting for duration of therapy, the odds of low bone mineral density (osteopenia or osteoporosis) with LHRH analogue was 4.5 (95%CI, 14.3 to 3.4); with anti-androgens was 5.9 (95%CI, 32.7 to 5); with orchiectomy was 7.3 (95%CI, 30 to 5.8) and multiple drugs was 9.2 ((95%CI, 31 to 7.1).

Conclusions

ADT is associated with lower BMD in Jamaican men on hormonal therapy for prostate cancer.

     

A comprehensive bone-health management approach for men with prostate cancer receiving androgen deprivation therapy

For advanced and metastatic prostate cancer, androgen deprivation therapy (adt) is the mainstay of treatment. Awareness of the potential bone-health complications consequent to adt use is increasing. Many studies have shown that prolonged adt leads to significant bone loss and increased fracture risk that negatively affect quality of life. Clinical practice guidelines for preserving bone health in men with prostate cancer on adt vary across Canada. This paper reviews recent studies on bone health in men with prostate cancer receiving adt and the current evidence regarding bone-health monitoring and management in reference to Canadian provincial guidelines. Based on this narrative review, we provide general bone-health management recommendations for men with prostate cancer receiving adt.     

Depression in men receiving androgen deprivation therapy for prostate cancer: a pilot study

PURPOSE: Prostate cancer is the most common malignancy in men and one of the leading causes of cancer death in men internationally. Treatment for prostate cancer frequently includes androgen deprivation therapy (ADT). Reports of depressive symptoms arising during ADT are emerging. This study examines the prevalence rates and risk factors associated with major depression in this population. METHOD: 45 men with prostate cancer receiving ADT at the MGH Cancer Center were surveyed for depression with the SCID for Axis I disorders for DSM-IV and the Beck Depression Inventory. RESULTS: Major depressive disorder was prevalent in 12.8% of the men with prostate cancer receiving ADT, eight times the national rate of depression in men, 32 times the rate in men over 65 years old. Major depression was not associated with worsening disease, medical response to ADT, receiving chemotherapy, or the type of ADT. Past history of depression was associated with current depression in this population (p<0.000). No first onset cases of depression occurred on ADT in this sample. CONCLUSION: This data suggests a significant rate of major depression in men with prostate cancer receiving ADT and that men with past histories of depression may be at particular risk for recurrence of their depression while undergoing this treatment.     

Intravenous nutrient therapy eliminated androgen deprivation therapy-induced hot flashes in two men with prostate cancer

Androgen deprivation therapy (ADT) is commonly used for the treatment of prostate cancer. For many undergoing ADT, hot flashes can affect and significantly reduce quality of life. Traditional medications for hot flashes are limited by both clinical effectiveness and side effects. In two case reports, ADT-induced hot flashes quickly resolved after a short course of a specific intravenous combination of vitamins and minerals. This therapeutic approach may have potential for the treatment of ADT-induced hot flashes.