Changes in resting-state measures of prostate cancer patients exposed to androgen deprivation therapy.
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SUBMITTER: Plata-Bello J
PROVIDER: S-EPMC8639725 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
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Changes in resting-state measures of prostate cancer patients exposed to androgen deprivation therapy.
Plata-Bello Julio J Plata-Bello Ana A Pérez-Martín Yaiza Y López-Curtis David D Acosta-López Silvia S Modroño Cristián C Concepción-Massip Tomás T
Scientific reports 20211202 1
The aim of the present work is to describe the differences in rs-fMRI measures (Amplitude of low frequency fluctuations [ALFF], Regional Homogeneity [ReHo] and Functional Connectivity [FC]) between patients exposed to Androgen deprivation therapy (ADT) and a control group. Forty-nine ADT patients and fifteen PC-non-ADT patients (Controls) were included in the study. A neuropsychological evaluation and a resting-state fMRI was performed to evaluate differences in ALFF and ReHo. Region of interest ...[more]
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Project description:ObjectivesAndrogen deprivation therapy (ADT) has seen increasing use as a prostate cancer treatment in recent years and has proven medically effective in numerous contexts. The treatment, however, is associated with a host of side effects including depression. Managing the psychological wellbeing of prostate cancer patients is important for maximizing their survival outcomes. Thus, this study aimed to evaluate depressive symptomatology in patients with androgen deprivation therapy (ADT) compared with that in patients who underwent prostatectomy and to explore the factors that affect depressive symptoms, which might occur during ADT.MethodsOne hundred and seven patients undergoing ADT (ADT group) and prostatectomy (Operation group) were enrolled. Adjustments were made for differences in characteristics between groups using a propensity score model with stabilized weights before treatment. Depressive symptoms between groups were compared using the Beck Depression Inventory (BDI) before treatment and six months after treatment initiation. To identify factors affecting depressive symptoms during ADT, multivariate regression analysis was performed on the mean change in BDI score, age, body mass index, testosterone level, prostate-specific antigen level, the international index of erectile function (IIEF), and the Gleason score.ResultsThe BDI score significantly increased in the ADT group compared to the operation group six months after treatment initiation (p < 0.001). Multivariate regression analysis revealed that before ADT, the BDI score was higher by 0.446 according to the IIEF. During ADT, the BDI score increased by 1.579 according to changes in BMI (p = 0.021) and decreased by 0.01 according to changes in testosterone levels (p = 0.034).ConclusionDepressive symptoms can be exacerbated in prostate cancer patients undergoing ADT. Efforts are needed to diagnose and treat depression appropriately, especially if depressive symptoms change in ADT patients with a high IIEF score before ADT, or reduced testosterone levels or increased BMI during ADT.
| S-EPMC7295190 | biostudies-literature
Project description:Androgen deprivation therapy (ADT) has been associated with a plethora of adverse effects, consistent with the androgen dependency of multiple reproductive and somatic tissues. One such tissue is the hemopoietic system, and one of the most predictable consequences of ADT is the development of anemia. Although anemia caused by ADT is rarely severe, ADT is often given to frail, elderly men with increased susceptibility to anemia due to multiple other causes. ADT-associated anemia may contribute to fatigue and reduced quality of life (QoL) in such men, although this requires further study. While anemia is an independent risk factor of mortality in men with prostate cancer, it is not known whether treatment of ADT-associated anemia alters clinically important outcomes, or whether treatment affects mortality. Awareness of the phenomenon of ADT-induced anemia should avoid unnecessary work-up in mild cases of normocytic normochromic anemia. However, assessment and treatment of more severe anemia may be required. This should be determined on an individual basis. In contrast to the well-described actions of ADT on erythropoiesis, its effect on other hemopoietic lineages has been less well elucidated. While preclinical studies have found roles for androgens in maturation and differentiated function of neutrophils, lymphocytes and platelets, the implications of these findings for men with prostate cancer receiving ADT require further studies.
| S-EPMC3735076 | biostudies-other
Project description:PurposeExcess fat mass (FM) contributes to poor prostate cancer (PCa) prognosis and comorbidity. However, FM gain is a common side effect of androgen deprivation therapy (ADT). We examined the efficacy of a 12-wk weight loss intervention to reduce FM and maintain lean mass (LM) in ADT-treated obese PCa patients.MethodsFourteen ADT-treated obese PCa patients (72 ± 9 yr, 39.7% ± 5.4% body fat) were recruited for a self-controlled prospective study, with 11 completing the 6-wk control period, followed by a 12-wk intervention comprising 300 min·wk-1 of exercise including supervised resistance training and home-based aerobic exercise, and dietitian consultations advising a daily energy deficit (2100-4200 kJ) and protein supplementation. Body composition was assessed by dual x-ray absorptiometry. Secondary outcomes included muscle strength (one-repetition maximum), cardiorespiratory fitness (maximal oxygen consumption), and blood biomarkers.ResultsThere were no significant changes during the control period. Patients attended 89% of supervised exercise sessions and 100% of dietitian consultations. No changes in physical activity or energy intake were observed. During the intervention, patients experienced significant reductions in weight (-2.8 ± 3.2 kg, P = 0.016), FM (-2.8 ± 2.6 kg, P < 0.001), and trunk FM (-1.8 ± 1.4 kg, P < 0.001), with LM preserved (-0.05 ± 1.6 kg, P = 0.805). Muscle strength (4.6%-24.7%, P < 0.010) and maximal oxygen consumption (3.5 ± 4.7 mL·min-1·kg-1, P = 0.041) significantly improved. Leptin significantly decreased (-2.2 (-2.7 to 0.5) ng·mL-1, P = 0.016) with no other changes in blood biomarkers such as testosterone and lipids (P = 0.051-0.765); however, C-reactive protein (rs = -0.670, P = 0.024) and triglycerides (r = -0.667, P = 0.025) were associated with individual changes in LM.ConclusionsThis study shows preliminary efficacy for an exercise and nutrition weight loss intervention to reduce FM, maintain LM, and improve muscle strength and cardiorespiratory fitness in ADT-treated obese PCa patients. The change in body composition may affect blood biomarkers associated with obesity and PCa progression; however, further research is required.
| S-EPMC7886363 | biostudies-literature
Project description:Androgen deprivation therapy (ADT) for prostate cancer increases fracture risk, decreases bone mineral density, and increases bone turnover markers (BTMs) including serum type 1 C-telopeptide (sCTX), tartrate-resistant alkaline phosphatase 5b (TRAP-5b), and procollagen-1 N-terminal telopeptide (P1NP). In a prespecified exploratory analysis of a phase 3, multicenter, double-blind study, we evaluated the effects of denosumab (60 mg subcutaneously every 6 months for 3 years) versus placebo (1468 patients, 734 in each group) on BTM values. BTMs were measured at baseline, month 1, and predose at months 6, 12, 24, and 36 in the overall population. BTMs at month 1 are also reported for subgroups based on age (< 70 years versus ≥ 70 years), prior duration of ADT (≤ 6 months versus > 6 months), and baseline BTM (≤ median versus > median BTM values). Treatment with denosumab provided a rapid and sustained decrease of BTM values compared with placebo. The median change in sCTX levels at month 1 was -90% in the denosumab group and -3% in the placebo group (p < 0.0001). The median change in TRAP-5b levels at month 1 was -55% in the denosumab group and -3% in the placebo group (p < 0.0001). The maximal median change in P1NP was -64% in the denosumab group and -11% in the placebo group, (p < 0.0001). Significantly greater decreases in BTM for denosumab were also seen in subgroup analyses based on age, prior ADT treatment, and baseline BTM values. Suppression of bone turnover markers was consistent with marked increases in bone mineral density reported previously.
| S-EPMC3222788 | biostudies-literature
Project description:PurposeTo characterize changes in lean body mass (LBM) in men with prostate cancer receiving androgen-deprivation therapy (ADT).Patients and methodsWe prospectively evaluated LBM in a prespecified substudy of a randomized controlled trial of denosumab to prevent fractures in men receiving ADT for nonmetastatic prostate cancer. LBM was measured by total-body dual-energy x-ray absorptiometry at study baseline and at 12, 24, and 36 months. The analyses included 252 patients (132, denosumab; 120, placebo) with a baseline and at least one on-study LBM assessment. Patients were stratified by age (< 70 v ≥ 70 years) and by ADT duration (≤ 6 v > 6 months).ResultsMedian ADT duration was 20.4 months at study baseline. Mean LBM decreased significantly from baseline, by 1.0% at month 12 (95% CI, 0.4% to 1.5%; P < .001; n = 248), by 2.1% at month 24 (95% CI, 1.5% to 2.7%; P < .001; n = 205), and by 2.4% at month 36 (95% CI, 1.6% to 3.2%; P < .001; n = 168). Men age ≥ 70 years (n = 127) had significantly greater changes in LBM at all measured time points than younger men. At 36 months, LBM decreased by 2.8% in men age ≥ 70 years and by 0.9% in younger men (P = .035). Men with ≤ 6 months of ADT at study entry (n = 36) had a greater rate of decrease in LBM compared with men who had received more than 6 months of ADT at study entry (3.7% v 2.0%; P = .0645).ConclusionIn men receiving ADT, LBM decreased significantly after 12, 24, and 36 months.
| S-EPMC3434987 | biostudies-literature
Project description:PurposeThis study aimed to explore the existing literature on frailty experienced by patients with prostate cancer (PC) receiving androgen deprivation therapy (ADT).Materials and methodsDatabase and manual searches were conducted to identify relevant studies published in English, with no limitation on the year of publication, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. Four databases-PubMed, Cochrane Library, EMBASE, and CINAHL-were used for database searches and reference lists, related journals, and Google Scholar were used for manual searches.ResultsA total of 12 studies were analyzed for this scoping review. Of these, only 2 were intervention studies, and 1 was a randomized controlled trial. Among the two intervention studies, the multidisciplinary intervention program, including psychological counseling, nutritional coaching, and supervised group physical exercise did not show significant improvement in frailty. In contrast, high-dose vitamin D supplementation significantly decreased frailty. The conceptual and operational definitions of frailty used in each study varied, and the most used one was mainly focused on physical functions. As a result of analyzing the other health-related variables associated with frailty in patients with PC receiving ADT, age, metastases, comorbidities, and incident falls were related to a high frailty level. As for the physiological index, high levels of C-reactive protein, and interleukin-6, and fibrinogen, low levels of total testosterone, lymphocyte count, and creatinine were associated with a high level of frailty. A few studies explored the relationship between psychological and cognitive variables and frailty.ConclusionsFurther research related to frailty in patients with PC receiving ADT should be conducted, and effective interventions to manage frailty should be developed. Additionally, research that considers not only the physical domain of frailty but also the psychological, cognitive, and social domains needs to be conducted.
| S-EPMC10949022 | biostudies-literature
Project description:ObjectiveAndrogen deprivation therapy (ADT) increases fracture risk in men with carcinoma of the prostate, but little is known about the fracture risk for different types of ADT. We studied the fracture risk amongst Chinese patients with carcinoma of the prostate prescribed different ADT regimens.Subjects and methodsThis was a single-centered observational study that involved 741 patients with carcinoma of the prostate from January 2001 to December 2011.ResultsAfter a median follow-up of 5 years, 71.7% of the study cohort received ADT and the incidence rate of fracture was 8.1%. Multivariable Cox regression analysis revealed that use of ADT was significantly associated with risk of incident fracture (Hazard Ratio [HR] 3.60; 95% Confidence Interval [95% CI] 1.41-9.23; p = 0.008), together with aged >75 years and type 2 diabetes. Compared with no ADT, all three types of ADT were independently associated with the risk of incident fracture: anti-androgen monotherapy (HR 4.47; 95% CI 1.47-13.7; p = 0.009), bilateral orchiectomy ± anti-androgens (HR 4.01; 95% CI 1.46-11.1; p = 0.007) and luteinizing hormone-releasing hormone agonists ± anti-androgens (HR 3.16; 95% CI 1.18-8.43; p = 0.022). However, there was no significant difference in the relative risks among the three types of ADT.ConclusionsFracture risk increases among all types of ADT. Clinicians should take into account the risk-benefit ratio when prescribing ADT, especially in elderly patients with type 2 diabetes.
| S-EPMC5291449 | biostudies-literature
Project description:Background The risk of cardiac dysfunction for patients with prostate cancer undergoing androgen deprivation therapy (ADT) in the real-world setting remains unclear. Methods and Results A total of 1120 patients with prostate cancer and a baseline echocardiography scan were identified from Chang Gung Research Database between January 1, 2001 and December 31, 2019. Patients were treated with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, or bilateral orchiectomy. Changes in left ventricular ejection fraction (LVEF) were further assessed in 421 patients using repeated measurements of LVEF before and during ADT treatment. The incidence of cancer therapy-related cardiac dysfunction (CT-RCD) was evaluated and defined as a ≥10% absolute decline in LVEF from baseline to a value of <53%. Among 421 patients undergoing ADT, LVEF declined from 66.3±11.3% to 62.5±13.6% (95% CI of mean difference: -5.0% to -2.7%) after a mean follow-up period of 1.6±0.8 years. CT-RCD occurred in 58 patients (13.7%) with a nadir LVEF of 40.3±9.1% after ADT. Lower baseline LVEF was significantly associated with CT-RCD (odds ratio, 1.07 [95% CI, 1.04-1.10]). The area under the curve of baseline LVEF for discriminating CT-RCD was 75.6%, with the corresponding optimal cutoff value of 64.5% (sensitivity, 79.3%; specificity, 67.2%). Conclusions ADT with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, and bilateral orchiectomy were associated with an increased risk of CT-RCD in patients with prostate cancer. In addition, lower baseline LVEF was a significant predictor of CT-RCD in patients with prostate cancer undergoing treatment with ADT.
| S-EPMC10727237 | biostudies-literature
Project description:Background and objectiveAndrogen deprivation therapy (ADT) is associated with reduced muscle and increased fat mass in patients with prostate cancer. However, the threshold for body composition changes associated with survival during ADT remains unclear. This study aimed to identify body composition change thresholds for all-cause mortality during ADT.MethodsWe enrolled 538 patients with prostate cancer (332 and 206 in the derivation and external validation cohorts, respectively) who underwent radiotherapy and ADT at two tertiary centers. Computed tomography (CT) images at baseline and 6 mo after ADT initiation were retrieved for an analysis. Skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured using CT at the L3 vertebral level. Optimal thresholds for body composition changes were determined using the Shapley Additive Explanations (SHAP) method and validated using a Cox proportional hazard model.Key findings and limitationsChanges in SMI, SATI, and VATI were the three most important features for predicting all-cause mortality. SMI change was inversely associated with the all-cause mortality risk, and changes in the SATI and VATI showed a U-shaped relationship with the all-cause mortality risk. SMI loss (≥4.0%), SATI gain (≥15.0%), and VATI gain (≥12.0%) were independently associated with an increased all-cause mortality risk (SMI loss: hazard ratio, 6.79, p < 0.001; SATI gain: hazard ratio: 2.95, p = 0.002; VATI gain: hazard ratio: 2.91, p < 0.001).Conclusions and clinical implicationsThe thresholds determined in this study can help identify patients with considerable body composition changes after 6 mo of ADT and guide interventions to improve body composition.Patient summaryWe identified muscle loss and increased adipose tissue thresholds associated with all-cause mortality during androgen deprivation therapy for men with prostate cancer. These thresholds can help guide interventions to improve body composition and potentially improve outcomes.
| S-EPMC11541424 | biostudies-literature
Project description:ContextAndrogen 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.ObjectiveReview 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 acquisitionA 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 synthesisData 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 (<72Gy) 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.ConclusionsAlthough 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 (<72Gy) in patients with high-risk tumors. Implementation of ADT should be evidence based, with special consideration to adverse events and the risk-benefit ratio.
| S-EPMC3483081 | biostudies-literature