Prostate cancer is the most common malignancy in older men. With the aging of the population, the number of older men with prostate cancer will grow rapidly. Androgen deprivation therapy (ADT) is the mainstay of treatment for men with systemic disease and is increasingly utilized as primary therapy or in combination with other therapies for localized disease. Side effects of therapy are multifold and include hot flashes, osteoporosis, and adverse psychological and metabolic effects. Recent research has illustrated that ADT can negatively impact the functional, cognitive, and physical performance of older men. Patients with prostate cancer, despite recurrence of the disease, have a long life expectancy and may be subjected to the side effects of ADT for many years. This review highlights the complications of ADT and approaches to management. We also provide recommendations for assessment and management of ADT complications among the most vulnerable and frail older male patients.
Disability; Geriatric assessment; Prostate cancer; Vulnerable elders; Functional impairment; Androgen deprivation; Quality of life; Complications
Early androgen deprivation therapy (ADT) has no proven survival advantage in older men with biochemical recurrence (BCR) of prostate cancer (PCa), and it may contribute to geriatric frailty; we tested this hypothesis.
We conducted a case-control study of men aged 60+ with BCR on ADT (n=63) versus PCa survivors without recurrence (n=71). Frailty prevalence, “obese” frailty, Short Physical Performance Battery (SPPB) scores and falls were compared. An exploratory analysis of frailty biomarkers (CRP, ESR, hemoglobin, albumin, and total cholesterol) was performed. Summary statistics, univariate and multivariate regression analyses were conducted.
More patients on ADT were obese (BMI >30; 46.2% vs. 20.6%; p=0.03). There were no statistical differences in SPPB (p=0.41) or frailty (p=0.20). Using a proposed “obese” frailty criteria, 8.7% in ADT group were frail and 56.5% were “prefrail”, compared with 2.9% and 48.8% of controls (p=0.02). Falls in the last year were higher in ADT group (14.3% vs. 2.8%; p=0.02). In analyses controlling for age, clinical characteristics, and comorbidities, the ADT group trended toward significance for “obese” frailty (p = 0.14) and falls (OR = 4.74, p = 0.11). Comorbidity significantly increased the likelihood of “obese” frailty (p=0.01) and falls (OR 2.02, p = 0.01).
Men with BCR on ADT are frailer using proposed modified “obese” frailty criteria. They may have lower performance status and more falls. A larger, prospective trial is necessary to establish a causal link between ADT use and progression of frailty and disability.
prostate cancer; biochemical recurrence; androgen deprivation therapy; frailty; older adults
A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.
In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals.
ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation.
Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.
Although motor features have been the defining element of essential tremor (ET), lower neurocognitive test scores are increasingly being recognized. However, the clinical correlates, if any, of these lower test scores remain largely unexplored.
To determine whether cognitive test scores in ET have any functional correlates.
The Modified Mini Mental Status Examination (MMSE), Katz Activities of Daily Living (ADL) scale and Lawton Instrumental (I) ADL scale were administered to 95 cases.
The Katz ADL score (rho = 0.26, p = 0.01) and Lawton IADL score (rho = 0.32, p = 0.001) were correlated with MMSE scores, such that poorer cognitive performance indicated greater dysfunction. Furthermore, cognitive test scores were a better predictor of functional disability than was tremor severity.
Poorer cognitive performance in ET was associated with greater functional deficit. Cognition should enter the clinical dialogue with ET patients as an issue of clinical significance.
essential tremor; cognition; dementia; mini mental status; functional disability; epidemiology; Alzheimer’s disease
The purpose of this study was to identify predictors of 3-month mortality in critically ill older persons under medical care and to assess the clinical impact of an ICU stay on physical and cognitive dependence and subjective health status in survivors.
We conducted a prospective observational cohort study including all older persons 75 years and older consecutively admitted into ICU during a one-year period, except those admitted after cardiac arrest, All patients were followed for 3 months or until death. Comorbidities were assessed using the Charlson index and physical dependence was evaluated using the Katz index of Activity of Daily Living (ADL). Cognitive dependence was determined by a score based on the individual components of the Lawton index of Daily Living and subjective health status was evaluated using the Nottingham Health Profile (NHP) score.
One hundred patients were included in the analysis. The mean age was 79.3 ± 3.4 years. The median Charlson index was 6 [IQR, 4 to 7] and the mean ADL and cognitive scores were 5.4 ± 1.1 and 1.2 ± 1.4, respectively, corresponding to a population with a high level of comorbidities but low physical and cognitive dependence. Mortality was 61/100 (61%) at 3 months. In multivariate analysis only comorbidities assessed by the Charlson index [Adjusted Odds Ratio, 1.6; 95% CI, 1.2-2.2; p < 0.003] and the number of organ failures assessed by the SOFA score [Adjusted Odds Ratio, 2.5; 95% CI, 1.1-5.2; p < 0.02] were independently associated with 3-month mortality. All 22 patients needing renal support after Day 3 died. Compared with pre-admission, physical (p = 0.04), and cognitive (p = 0.62) dependence in survivors had changed very little at 3 months. In addition, the mean NHP score was 213.1 ± 132.8 at 3 months, suggesting an acceptable perception of their quality of life.
In a selected population of non surgical patients 75 years and older, admission into the ICU is associated with a 3-month survival rate of 38% with little impact on physical and cognitive dependence and subjective health status. Nevertheless, a high comorbidity level (ie, Charlson index), multi-organ failure, and the need for extra-renal support at the early phase of intensive care could be considered as predictors of death.
older persons; intensive care unit; mortality; functional autonomy; quality of life
Despite a lack of consensus regarding effectiveness, androgen deprivation therapy (ADT) is a common treatment for non-metastatic, low-risk prostate cancer. To examine a particular clinical concern regarding the possible impact of ADT on cognition, the current study combined neuropsychological testing with functional magnetic resonance imaging (fMRI) to assess both brain activation during cognitive performance as well as the integrity of brain connectivity.
In a prospective observational cohort analysis of men with non-metastatic prostate cancer at a Veterans Affairs medical center, patients receiving ADT were compared with patients not receiving ADT at baseline and at 6 months. Assessments included fMRI, the N-back task (for working memory), the stop-signal task (for cognitive control), and a quality of life questionnaire.
Among 36 patients enrolled (18 in each group), 30 completed study evaluations (15 in each group); 5 withdrew participation and 1 died. Results for the N-back task, stop-signal task, and quality of life were similar at 6 months vs. baseline in each group. In contrast, statistically significant associations were found between ADT use (vs. non use) and decreased medial prefrontal cortical activation during cognitive control, as well as decreased connectivity between the medial prefrontal cortex and other regions involved with cognitive control.
Although ADT for 6 months did not affect selected tests of cognitive function, brain activations during cognitive control and functional brain connectivity were impaired on fMRI. The long-term clinical implications of these changes are not known and warrant future study.
Androgen deprivation; Prostate cancer; Brain function; Cognitive function
Treatment with Androgen Deprivation Therapy (ADT) for prostate cancer is associated with changes in body composition including increased fat and decreased lean mass; increased fatigue, and a reduction in quality of life. No study to date has evaluated the effect of dietary and physical activity modification on the side-effects related to ADT. The aim of this study is to evaluate the efficacy of a 6-month dietary and physical activity intervention for prostate cancer survivors receiving ADT to minimise the changes in body composition, fatigue and quality of life, typically associated with ADT.
Men are recruited to this study if their treatment plan is to receive ADT for at least 6 months. Men who are randomised to the intervention arm receive a home-based tailored intervention to meet the following guidelines a) ≥ 5 servings vegetables and fruits/day; b) 30%-35% of total energy from fat, and < 10% energy from saturated fat/day; c) 10% of energy from polyunsaturated fat/day; d) limited consumption of processed meats; e) 25-35 gm of fibre/day; f) alcoholic drinks ≤ 28 units/week; g) limited intake of foods high in salt and/or sugar. They are also encouraged to include at least 30 minutes of brisk walking, 5 or more days per week. The primary outcomes are change in body composition, fatigue and quality of life scores. Secondary outcomes include dietary intake, physical activity and perceived stress. Baseline information collected includes: socio-economic status, treatment duration, perceived social support and health status, family history of cancer, co-morbidities, medication and supplement use, barriers to change, and readiness to change their health behaviour. Data for the primary and secondary outcomes will be collected at baseline, 3 and 6 months from 47 intervention and 47 control patients.
The results of this study will provide detailed information on diet and physical activity levels in prostate cancer patients treated with ADT and will test the feasibility and efficacy of a diet and physical activity intervention which could provide essential information to develop guidelines for prostate cancer patients to minimise the side effects related to ADT.
ISRCTN trial number ISCRTN75282423
Little is known about the long-term impact of androgen deprivation therapy (ADT) on body composition in men with prostate cancer. We compared body composition parameters in men with non-metastatic prostate cancer on or not on therapy with healthy, age-matched controls at baseline and monitored changes over a 2-year period.
We measured body fat mass and lean body mass in 81 men with prostate cancer on no ADT, 43 men on acute ADT (less than 6 months), 67 men on chronic ADT (more than 6 months) and 53 age-matched healthy controls. Measurements were performed every 6 months for 2 years.
Men with prostate cancer on acute ADT (mean 3 months) had significant gains in body fat mass [1499.56 ± 322.28 g (mean ± S.E.) after 12 months, 2167.15 ± 676.45 g after 24 months, p < 0.01 for both] and losses in lean body mass (929.74 ± 296.36 g after 12 months, 1785.81 ± 501.31 g after 24 months, p < 0.01 for both) over 2 years. Men on chronic ADT (mean 31 months) had smaller but still significant body composition changes over 24 months. Changes in body composition in men on no ADT were small and healthy controls had no significant changes.
Men with prostate cancer on ADT have significant gains in body fat mass and losses lean body mass over 2 years. These changes are most pronounced with initiation of ADT.
Prostate cancer; Androgen deprivation therapy; Body composition; Dual-energy X-ray absorptiometry
Androgen deprivation therapy (ADT) is first-line therapy for patients with prostate cancer (PCA) who experience biochemical recurrence (BCR). However, the optimal timing of ADT initiation is uncertain, and earlier ADT initiation can cause toxicities that lower quality of life (QOL). We tested the hypothesis that elevated cancer anxiety leads to earlier ADT initiation for BCR in older men.
Patients and Methods
We conducted a prospective cohort study of older patients with BCR of PCA (n = 67). Patients completed questionnaires at presentation and each follow-up visit until initiation of ADT. PCA-specific anxiety was measured with the Memorial Anxiety Scale for Prostate Cancer (MAX-PC). Other collected data included demographics, clinical information, and general anxiety information. Treating oncologists were surveyed about their recommendations for ADT initiation. The primary outcome was the time to ADT initiation. Univariate, multivariate logistic regression, and time-to-event analyses were conducted to evaluate whether cancer anxiety was a predictor of earlier initiation of ADT.
Thirty-three percent of patients initiated ADT at the first or second clinic visit. Elevated PCA anxiety (MAX-PC > 16) was the most robust predictor in multivariate analyses of early initiation (odds ratio [OR], 9.19; P = .01). PSA also independently correlated with early initiation (OR, 1.31; P = .01). PSA did not correlate with MAX-PC.
Cancer anxiety independently and robustly predicts earlier ADT initiation in older men with BCR. For older patients with PCA, earlier ADT initiation may not change life expectancy and can negatively impact QOL. PCA-specific anxiety is a potential target for a decision-making intervention in this setting.
Men with PSA-only relapse of prostate cancer after primary therapy are generally fully functional and asymptomatic with a life expectancy of up to ten or more years. Androgen deprivation therapy (ADT) is a common treatment option. This study examined mood and cognitive changes in otherwise healthy men with prostate cancer prior to, during and after ADT.
Twenty hormone naïve, eugonadal prostate cancer patients without evidence of metastases and with a rising PSA were treated with intermittent ADT consisting of nine months of complete androgen blockade achieved with combined leuprolide and flutamide followed by an “off treatment” period. Cognitive function tests and mood measures were administered at baseline, after three and nine months of ADT and after three months of no treatment. Twenty healthy control patients without prostate cancer range matched for age and education were tested at the same time intervals.
ADT patients evidenced a significant decline in spatial reasoning, spatial abilities and working memory during treatment compared to baseline. No changes were noted for measures of verbal or spatial memory, selective attention or language. Significant changes in self-rated mood such as increased depression, tension, anxiety, fatigue and irritability were evident during treatment compared to baseline for ADT patients. No significant changes in either cognitive tests or mood measures were noted for the healthy control group.
These findings, suggest that nine months of combined androgen blockade may result in some adverse changes in cognition and mood. However, many but not all of these changes can return to baseline after cessation of ADT.
Cancer; Oncology; Complete Androgen Blockade (CAB); Mood; Cognition; Memory; Prostate Cancer; Testosterone; Flutamide; Intermittent Androgen Ablation Therapy (ADT)
More than one-third of the estimated 2 million prostate cancer survivors in the United States receive androgen deprivation therapy (ADT). This population of mostly older men is medically vulnerable to a variety of treatment-associated adverse effects.
MEASUREMENTS AND RESULTS
Androgen-deprivation therapy (ADT) causes loss of libido, vasomotor flushing, anemia, and fatigue. More recently, ADT has been shown to accelerate bone loss, increase fat mass, increase cholesterol and triglycerides, and decrease insulin sensitivity. Consistent with these adverse metabolic effects, ADT has also recently been associated with greater risks for fractures, diabetes and cardiovascular disease.
Primary care clinicians and patients should be aware of the potential benefits and harms of ADT. Screening and intervention to prevent treatment-related morbidity should be incorporated into the routine care of prostate cancer survivors. Evidence-based guidelines to prevent fractures, diabetes, and cardiovascular disease in prostate cancer survivors represent an important unmet need. We recommend the adapted use of established practice guidelines designed for the general population.
prostate cancer; survivorship; GnRH agonists; osteoporosis; bisphosphonates; diabetes; obesity; cardiovascular disease
To determine the impact of adjuvant androgen deprivation therapy (ADT) for patients who have node-positive prostate cancer in the prostate-specific antigen (PSA) era.
Patients and Methods
We used linked Surveillance, Epidemiology and End Results-Medicare data to construct a cohort of men who underwent radical prostatectomy (RP) between 1991 and 1999 and who had positive regional lymph nodes. We classified men as receiving adjuvant ADT if they received ADT within 120 days of RP, and we compared them to the men who had not received adjuvant ADT. We used propensity scores to balance potential confounders of receiving adjuvant ADT (ie, tumor characteristics, extent of nodal disease, demographics, receipt of radiation therapy) and Cox proportional hazard methods to measure the impact of adjuvant ADT on overall survival (OS), stratified by propensity score quintile. We conducted a sensitivity analysis that used 90, 150, 180, and 365 days as the definition for adjuvant ADT.
A total of 731 men were identified, 209 of whom received ADT within 120 days of RP. There was no statistically significant difference in OS between the adjuvant ADT and non-ADT group (HR, 0.97; 95% CI, 0.71 to 1.27). There was no statistically significant survival difference with 90, 150, 180, and 365 days as the adjuvant ADT definition.
Deferring immediate ADT in men with positive lymph nodes after RP may not significantly compromise survival. Because observational studies should be considered hypothesis-generating studies, these results should be validated in a prospective fashion in a similar patient population.
Androgen deprivation therapy (ADT) is the mainstay therapy for men with prostate cancer. However, there are musculoskeletal side effects from ADT that increase the risk for osteoporosis and fracture, and can compromise the quality of life of these individuals. The objectives of this study are to determine the efficacy of a home-based walking exercise program in promoting bone health, physical function and quality of life in men with prostate cancer receiving ADT.
A 12-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Sixty men with prostate cancer who will be 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 12-month home-based walking exercise program, while the Control Group will receive standard medical advice from the attending physician. A number of outcome measures will be used to assess bone health, physical function, and health-related quality of life. At baseline and 12 months, bone health will be assessed using dual-energy X-ray absorptiometry. At baseline and every 3 months up to 12 months, physical function will be evaluated using the Functional Assessment of Chronic Illness Therapy - Fatigue Scale, Activities-specific Balance Confidence Scale, Short Physical Performance Battery, and Six-Minute Walk Test; and health-related quality of life will be assessed using the Functional Assessment of Cancer Therapy Prostate Module and the Medical Outcomes Study 12-item Short Form Health Survey Version 2. A mixed multiple analysis of variance will be used to analyze the data.
Musculoskeletal health management remains a challenge in men with prostate cancer receiving ADT. This study addresses this issue by designing a simple and accessible home-based walking exercise program that will potentially have significant impact on reducing the risk of fracture, promoting physical function, and ultimately improving the health-related quality of life in men with prostate cancer receiving ADT.
Prostate cancer; Androgen deprivation therapy; Walking; Home-based exercise; Bone health; Physical function; Quality of life
To examine whether activity restriction specifically induced by fear of falling (FF) contributes to greater risk of disability and decline in physical function.
Prospective cohort study.
Population-based older cohort.
Six hundred seventy-three community-living elderly (≥65) participants in the Invecchiare in Chianti Study who reported FF.
FF, fear-induced activity restriction, cognition, depressive symptoms, comorbidities, smoking history, and demographic factors were assessed at baseline. Disability in activities of daily living (ADLs) and instrumental activities of daily living (IADLs) and performance on the Short Performance Physical Battery (SPPB) were evaluated at baseline and at the 3-year follow-up.
One-quarter (25.5%) of participants did not report any activity restriction, 59.6% reported moderate activity restriction (restriction or avoidance of <3 activities), and 14.9% reported severe activity restriction (restriction or avoidance of ≥3 activities). The severe restriction group reported significantly higher IADL disability and worse SPPB scores than the no restriction and moderate restriction groups. Severe activity restriction was a significant independent predictor of worsening ADL disability and accelerated decline in lower extremity performance on SPPB over the 3-year follow-up. Severe and moderate activity restriction were independent predictors of worsening IADL disability. Results were consistent even after adjusting for multiple potential confounders.
In an elderly population, activity restriction associated with FF is an independent predictor of decline in physical function. Future intervention studies in geriatric preventive care should directly address risk factors associated with FF and activity restriction to substantiate long-term effects on physical abilities and autonomy of older persons.
fear of falling; activity restriction; aging; disability; physical function
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.
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.
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.
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.
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.
Prostate cancer; Androgen deprivation; Hormone treatment; Adverse effects
The potential association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM) remains controversial. This study assessed mortality outcomes in a large national registry to further elucidate the association between treatment selection and cause of mortality.
Patients and Methods
A total of 7,248 men in the CaPSURE registry were analyzed. Treatment was categorized as local only, primary ADT monotherapy, local treatment plus ADT, and watchful waiting/active surveillance (WW/AS). Competing hazards survival analysis was performed for prostate cancer–specific mortality (PCSM), CVM, and all-cause mortality. A propensity score–adjusted and a propensity-matched analysis were undertaken to adjust for imbalances in covariates among men receiving various treatments.
Patients treated with ADT or WW/AS had a higher likelihood of PCSM than those treated with local therapy alone. Patients treated with primary ADT had an almost two-fold greater likelihood of CVM (HR, 1.94; 95% CI, 1.29 to 2.97) than those treated with local therapy alone; however, patients treated with WW/AS had a greater than two-fold increased risk of CVM (HR, 2.46; 95% CI, 1.53 to 3.95). A propensity-matching algorithm in a subset of 1,391 patients was unable to find a significant difference in CVM between those who did or did not receive ADT.
Patients matched on propensity to receive ADT did not show an association between ADT and CVM. This suggests that potential unmeasured variables affecting treatment selection may confound the relationship between ADT use and cardiovascular risk. However, an association may yet exist, because the propensity score could not include all known risk factors for CVM.
Randomized data have supported the use of long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) for men with high-risk prostate cancer. The present study reviewed the outcomes of intermediate- and high-risk men treated with RT and short-term ADT.
Materials and Methods
A total of 184 men with any single risk factor of prostate-specific antigen ≥10 ng/mL, clinical Stage T2b or greater, or Gleason score ≥7 were treated with primary external beam RT for nonmetastatic adenocarcinoma of the prostate. The median radiation dose was 74 Gy; 55% were treated with intensity-modulated RT. All patients received ADT for 1 to 6 months (median, 4), consisting of a gonadotropin-releasing hormone analog. Univariate and multivariable analyses were performed for risk factors, including T stage, Gleason score, radiation dose, and prostate-specific antigen level.
With a median follow-up of 51 months, the 4-year freedom from biochemical failure (FFBF) using the nadir plus 2 ng/mL definition was 83% for all patients. Clinical Stage T3 disease was the only variable tested associated with FFBF on univariate (4-year FFBF rate, 46% vs. 87% for Stage T1-T2c disease; p = .0303) and multivariable analysis (hazard ratio, 3.9; p = .0016). On a subset analysis of high-risk patients (National Comprehensive Cancer Network criteria), those with clinical Stage T3 disease (4-year FFBF rate, 46% vs. 80%; p = .0303) and a radiation dose <74 Gy (4-year FFBF rate, 64% vs. 80%) had a poorer outcome on univariate analysis. However, clinical Stage T3 disease and radiation dose were not significant on multivariable analysis, although a statistical multivariable trend was seen for both (p = .0650 and p = .0597, respectively).
Short-term ADT and RT might be acceptable for men with intermediate- and high-risk prostate cancer, especially for clinically localized disease treated with doses of ≥74 Gy.
Prostate cancer; radiotherapy; hormonal therapy
This study examined differences between men and women in the ability to perform basic activities of daily living, instrumental activities of daily living, and higher physical functioning after stroke. The objective of the study was to determine whether sex differences in stroke recovery can be explained by depressive status beyond older age, stroke severity, prestroke physical functioning, and other medical comorbidities.
A total of 459 stroke patients were recruited from acute and subacute facilities in an urban midwestern community. These patients were followed prospectively from stroke onset until 6 months poststroke. All study participants were assessed using standardized stroke outcome measures, including the National Institutes of Health Stroke Scale, the Barthel Activities of Daily Living Index, the Lawton Instrumental Activities of Daily Living scale, and the SF-36 Health Survey physical functioning scale. The Geriatric Depression Scale was used to assess depressive status. Each outcome was measured at baseline (within 2 weeks of stroke onset), as well as 1, 3, and 6 months poststroke. Prestroke physical functioning, stroke characteristics, and comorbidities were also assessed at baseline.
Female patients in the study were older than male patients, with a mean age of 71 years for women vs 69 years for men. Female patients reported lower prestroke physical functioning than their male counterparts. Six months after stroke, women in the study were less likely than the men to achieve a score of ?95 on the Barthel Activities of Daily Living Index (hazards ratio [HR] = 0.68; 95% confidence interval [CI], 0.52–0.90), carry out eight of nine instrumental activities of daily living without assistance (HR = 0.46; 95% CI, 0.30–0.68), and score ?90 on the SF-36 Health Survey physical functioning scale (HR = 0.54; 95% CI, 0.28–1.01). When age, prestroke physical functioning, stroke severity, and depressive status at baseline were controlled in the analysis, women in the study continued to be less likely (HR = 0.51; 95% CI, 0.32–0.79) than men in the study to be able to carry out eight of nine instrumental activities of daily living completely without assistance, but there were no observed sex differences in achievement of independence in basic activities of daily living or higher physical functioning.
Prestroke physical functioning and depressive symptoms are important factors in the investigation of sex differences in stroke recovery. Lower recovery of activities of daily living and physical functioning in women after stroke may be due to multifactorial effects of older age, poor physical function prior to stroke onset, and depressive status after stroke.
To better understand the natural history of weight change with androgen-deprivation therapy (ADT), we investigated the effect of ADT on body weight among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.Men undergoing ADT lose lean muscle but gain fat mass, contributing to an overall gain in weight.
PATIENTS AND METHODS
We identified 132 men in SEARCH who received ADT after radical prostatectomy.‘Weight change’ was defined as the difference in weight before starting ADT (6 months before ADT) and the on-ADT weight (between 6 and 18 months after starting ADT).In a subanalysis, baseline characteristics of weight-gainers and -losers were analysed using univariate and multivariate analysis to test association with weight change.
In all, 92 men (70%) gained weight, and 40 (30%) either lost or maintained a stable weight.On average, weight on ADT was 2.2 kg higher than the weight before ADT, with the mean change for weight-gainers and -losers being +4.2 kg and −2.4 kg, respectively.This compared with no significant weight change in the year before starting ADT (paired t-test, change −0.7 kg, P = 0.19) or in the second year on ADT (paired t-test, change −0.5 kg, P = 0.46) for 84 men in whom these additional weight values were recorded.There was no significant association between any of the features examined and weight change on univariate and multivariate analysis.
In this longitudinal study, ADT was accompanied by significant weight gain (+2.2 kg). This change occurred primarily in the first year of therapy, with men neither losing nor gaining additional weight thereafter.
prostate cancer; androgen deprivation; side-effects; weight
Androgen deprivation therapy (ADT) has become the cornerstone of treatment for both advanced and non-metastatic prostate cancer. The presence of a non-traumatic vertebral fracture (VF) identifies a patient who has clinical osteoporosis. Vertebral Fracture Analysis (VFA), a dual-energy X-ray absorptiometry (DXA)-based technology identifies VFs in conjunction with a standard bone mineral densitometry (BMD) exam. The objective of this study is to determine if VFA will increase the diagnosis of osteoporosis in men with prostate cancer on ADT.
Materials and Methods
116 men ≥ 60 years of age with non-metastatic prostate cancer receiving androgen-deprivation therapy (ADT) for ≥ 6 months underwent DXA of the spine, hip, and one-third distal radius, VFA), and conventional vertebral x-rays.
Approximately 40% of the men had clinically defined osteoporosis. The use of conventional DXA criteria (spine and hip) alone resulted in the misdiagnosis of approximately 75% of patients. VFA and addition of the one-third distal radius site performed by DXA both increased the rate of diagnosis and reduces the misclassification of osteoporosis in men with prostate cancer, compared to conventional DXA criteria alone. Analysis indicated that VFA assessment of mild, moderate, and severe fractures from all readable vertebrae (T5-L4) had a kappa, sensitivity, and specificity of 0.92, 100% and 95%, respectively, with semi-quantitative radiography.
Men with prostate cancer on ADT should be screened for osteoporosis at the initiation of therapy, and evaluation should include DXA of the one-third distal radius in addition to the spine and hip, as well as evaluation for VFs.
androgen deprivation therapy; vertebral fractures; vertebral fracture assessment; osteoporosis; bone mineral density
Currently, there is one Behçet's disease (BD) specific self reporting questionnaire developed and published in the literature, The Leeds BD-quality of life (QoL). We conducted a cross-cultural adaptation and validation of the Arabic version of the Leeds BD-QoL
A cross-sectional study was conducted among 41 consecutive patients attending rheumatology clinics at the American University of Beirut Medical Center between June and December 2007. The BD-QoL questionnaire, the Katz Index of Activities of Daily Living (ADL) and the Lawton Instrumental Activities of Daily Living (IADL) questionnaires were co-administered during the same visit, and severity scores were calculated. Cross-cultural adaptation of BD-QoL was performed using forward and backward translations of the original questionnaire. Internal consistency and test-retest reliability of the final version were determined. Exploratory Factor Analysis (EFA) was used to assess the dimensionality of the scale items. External construct validity was examined by correlating Arabic BD-QoL with the severity score, ADL and IADL.
The 30 items of the adapted Arabic BD-QoL showed a high internal consistency (KR-20 coefficient 0.89) and test-retest reliability (Spearman's test 0.91). The convergence of all 30 items suggests that the 30-item adapted Arabic BD-QoL scale is unidimensional. BD-QoL did not correlate with any of the patients' demographics. Still, it was positively correlated with patient severity score (r 0.4, p 0.02), and IADL (but not ADL).
This cross-cultural adaptation has produced an Arabic BD-QoL questionnaire that is now available for use in clinical settings and in research studies, among Arabic speaking patients.
Behçet's disease; Quality of life; Arabic version of BD-QoL; Cross-cultural adaptation; Validity and reliability
To determine whether participants with mild cognitive impairment (MCI) differ from cognitively normal (NC) older adults on traditional and novel informant-based measures of activities of daily living (ADL) and to identify cognitive correlates of ADLs among participants with MCI.
University medical setting.
Seventy-seven participants (NC: N = 39; MCI: N = 38), 60 to 90 years old (73.5 ± 6.6 years; 53% female).
Neuropsychological and ADL measures.
Neuropsychological tests were administered to NC and MCI participants. Informants completed the Lawton and Brody Instrumental Activities of Daily Living and Physical Self-Maintenance Scale, including instrumental (IADL) and basic ADL (BADL) scales, as well as the Functional Capacities for Activities of Daily Living (FC-ADL), an error-based ADL measure.
No statistically or clinically significant between-group differences emerged for the BADL or IADL subscales. However, a robust difference was noted for the FC-ADL scale (MCI errors > NC errors; F(1,75) = 13.6, p <0.001; d = 0.84). Among MCI participants, correlations revealed that a measure of verbal learning was the only neuropsychological correlate of FC-ADL total score (r =-0.39, df = 36, p = 0.007). No neuropsychological measures were significantly associated with the IADL or BADL subscale score.
Traditional measures assessing global ADLs may not be sensitive to early functional changes related to MCI; however, error-based measures may capture the subtle evolving functional decline associated with MCI. Among MCI participants, early functional difficulties are associated with verbal learning performance, possibly secondary to the hallmark cognitive impairment associated with this cohort.
Instrumental activities of daily living; MCI; memory; functional errors; neuropsychology
To investigate the effect of efforts in the early detection of prostate cancer using prostate-specific antigen (PSA) testing in the USA, by estimating the regional prevalence of androgen deprivation therapy (ADT) among older men in 1993–2000, and correlating the prevalence with early detection and aggressive treatment rates in 1987–91, as some authors predicted that ADT, a treatment traditionally reserved for advanced prostate cancer, would become less common over time as a result of such efforts.
PATIENTS AND METHODS
A sample of 5% of men who were Medicare beneficiaries was used in this prospective population-based cohort study. The main outcome measures were the overall prevalence of ADT (medical and surgical) in the cohort from 1993 to 2000, and correlations between rates of prostate procedures in the 306 USA hospital referral regions in 1987–91 and prevalence of ADT in those regions from 1993 to 2000.
The prevalence of ADT among these men in the USA increased steadily from 1.8% in 1993 to 2.9% in 2000 (P < 0.001). Regions with higher rates of prostate biopsy in 1987–91 had a higher prevalence of ADT in 1993, 1995 and 1997 (P < 0.05). Regions with higher rates of transurethral prostatectomy in 1987–91 had a higher prevalence of ADT in 1993–2000 (P < 0.01). Regions with higher rates of radical prostatectomy in 1987–91 had higher rates of ADT in 1993–99 (P < 0.05).
Widespread early detection and aggressive treatment for prostate cancer in the USA has been associated with more, not less, ADT among older men over time.
prostate cancer; androgen deprivation; epidemiology; prostate-specific antigen
Androgen deprivation therapy (ADT) is accompanied by a number of adverse side effects including reduced bone mass and increased risk for fracture, reduced lean mass and muscle strength, mood disturbance and increased fat mass compromising physical functioning, independence, and quality of life. The purpose of this investigation is to examine the effects of long term exercise on reversing musculoskeletal-related side effects, and cardiovascular and diabetes risk factors in men receiving androgen deprivation for their prostate cancer. Specifically, we aim to investigate the effects of a 12-month exercise program designed to load the musculoskeletal system and reduce cardiovascular and diabetes disease progression on the following primary endpoints: 1) bone mineral density; 2) cardiorespiratory function and maximal oxygen capacity; 3) body composition (lean mass and fat mass); 4) blood pressure and cardiovascular function; 5) lipids and glycemic control; and 6) quality of life and psychological distress.
Multi-site randomized controlled trial of 195 men (65 subjects per arm) undergoing treatment for prostate cancer involving ADT in the cities of Perth and Brisbane in Australia. Participants will be randomized to (1) resistance/impact loading exercise, (2) resistance/cardiovascular exercise groups and (3) usual care/delayed exercise. Participants will then undergo progressive training for 12 months. Measurements for primary and secondary endpoints will take place at baseline, 6 and 12 months (end of the intervention).
The principal outcome of this project will be the determination of the strength of effect of exercise on the well established musculoskeletal, cardiovascular and insulin metabolism side effects of androgen deprivation in prostate cancer patients. As this project is much longer term than previous investigations in the area of exercise and cancer, we will gain knowledge as to the continuing effects of exercise in this patient population specifically targeting bone density, cardiovascular function, lean and fat mass, physical function and falls risk as primary study endpoints. In terms of advancement of prostate cancer care, we expect dissemination of the knowledge gained from this project to reduce fracture risk, improve physical and functional ability, quality of life and ultimately survival rate in this population.
Clinical Trial Registry
A Phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer; ACTRN12609000200280
Therapeutic strategy remains unclear with no clear consensus for men with high-risk prostate cancer after radical prostatectomy. We aimed to evaluate into a prospective randomized trial the effectiveness and the feasibility of adjuvant weekly paclitaxel combined with androgen deprivation therapy (ADT) in these patients. 47 patients with high risk prostate cancer were randomized 6 weeks after radical prostatectomy: ADT alone versus combination of ADT and weekly paclitaxel. Toxicity, quality-of-life and functional results were compared between the two arms. All 23 patients completed 8 cycles of paclitaxel. Toxicity was predominantly of grade 1–2 severity. There were no differences in EORTC QLQ-C30 scores between the two groups and between baseline and last assessment at 24 months after surgery. Urinary continence was complete at one year after surgery for all patients and no significant differences was noted at each assessment between the two groups. The interim analysis of this trial confirms the feasibility of weekly paclitaxel in combination with androgen deprivation therapy in men at high risk prostate cancer with curative intent. This adjuvant combined therapy does no alter quality-of-life and continence recovery after surgery plus ADT. A larger cohort is awaited to determine the oncological outcomes of this strategy.
Aged; Androgen Antagonists; therapeutic use; Combined Modality Therapy; Humans; Male; Middle Aged; Paclitaxel; adverse effects; therapeutic use; Pilot Projects; Prostate; pathology; Prostate-Specific Antigen; analysis; Prostatectomy; Prostatic Neoplasms; drug therapy; surgery; Risk; Urinary Incontinence; chemically induced; prostate cancer; radical prostatectomy; high risk; adjuvant chemotherapy; paclitaxel