-
Supportive Care in Cancer : Official... Apr 2021Androgen deprivation therapy (ADT) is a treatment used in men with prostate cancer (PCa); however it is responsible for many adverse effects, with negative impact on...
PURPOSE
Androgen deprivation therapy (ADT) is a treatment used in men with prostate cancer (PCa); however it is responsible for many adverse effects, with negative impact on quality of life. ADT causes loss of bone mineral density (BMD) and skeletal muscle mass, alteration of body composition, and cognitive function, which altogether lead to increased risk of accidental falls and fractures. This systematic review analyses the effectiveness of physical exercise (PE) in preventing accidental falls and fractures and reducing the loss of BMD in men with PCa receiving ADT.
METHODS
We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for articles between database inception and September 2, 2020. Eligible studies included randomized controlled trials (RCTs) investigating the effects of exercise on bone health in men with PCa receiving ADT.
RESULTS
Nine RCTs were included. Experimental PE consisted in multicomponent programmes that involved aerobic, resistance, impact-loading exercise, and football training. None of the RCTs investigated the risk of accidental falls and fractures, while two trials reported beneficial effects of PE on lumbar spine, hip, and femoral shaft BMD. No further significant difference was detected in the outcomes investigated.
CONCLUSION
Evidence of the effectiveness of PE to prevent the risk of accidental falls and fractures and BMD loss is lacking. Nevertheless, clinical guidelines recommend PE as a part of the clinical management of men with PCa receiving ADT due to its known numerous health benefits. Research should focus on PE strategies to prevent accidental falls, a clinically relevant outcome in this vulnerable population.
TRIAL REGISTRATION
The study protocol was registered with International Prospective Register of Systematic Reviews (PROSPERO, number CRD 42020158444 ) on 04/28/2020.
Topics: Aged; Androgen Antagonists; Bone Density; Bone and Bones; Exercise; Exercise Therapy; Humans; Male; Prostatic Neoplasms
PubMed: 33119791
DOI: 10.1007/s00520-020-05830-1 -
International Journal of Transgender... 2020Gender-affirming hormone therapy for transgender women includes estrogen and antiandrogens (cyproterone acetate, spironolactone, or gonadotropin-releasing hormone... (Review)
Review
BACKGROUND
Gender-affirming hormone therapy for transgender women includes estrogen and antiandrogens (cyproterone acetate, spironolactone, or gonadotropin-releasing hormone agonists). Both estrogen and antiandrogens are reported to increase prolactin levels. The objective is to systematically review the evidence of the effects of antiandrogens on prolactin levels, hyperprolactinemia, and prolactinomas among transgender women on estrogen therapy.
METHODS
We searched PubMed, Embase, and PsycInfo up to May 2020. We included studies with at least 3 months follow-up that evaluated the effects of antiandrogens among transgender women and reported on prolactin levels, hyperprolactinemia, or image-confirmed prolactinomas. Two reviewers independently screened studies for eligibility, serially abstracted data, and independently assessed risk of bias and graded strength of evidence.
FINDINGS
We included 17 studies (16 publications): 8 prospective cohorts, 8 retrospective cohorts, and 1 cross-sectional study, each with a moderate to serious risk of bias. Among transgender women on estrogen, prolactin levels increased by over 100% with cyproterone acetate and by up to 45% with spironolactone. However, we were unable to isolate the effects of antiandrogens from estrogen therapy. We were unable to draw conclusions about effects of antiandrogens on hyperprolactinemia and prolactinomas.
INTERPRETATION
Prolactin levels may be increased in transgender women who are taking both estrogens and an antiandrogen. Future research is needed to determine the effects of different antiandrogens on prolactin levels separately from estrogen therapy. Ideally, future studies would be prospective, provide either a comparison of two different antiandrogens or compare combination of estrogen and antiandrogen therapy to estrogen alone, and control for possible confounders.
PubMed: 34993517
DOI: 10.1080/15532739.2020.1819505 -
International Journal of Clinical... Nov 2020Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation androgen receptor inhibitors. However,... (Meta-Analysis)
Meta-Analysis
Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation androgen receptor inhibitors. However, direct comparative data are not available to inform treatment decisions and/or guideline recommendations. Therefore, we performed network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or metastasis-free and/or prostate-specific antigen (PSA) progression-free survival (OS/MFS/PSA-PFS) and/or adverse events (AEs) in nmCRPC patients were considered eligible. Three studies (n = 4117) met our eligibility criteria. Formal network meta-analyses were conducted. For MFS, apalutamide, darolutamide, and enzalutamide were significantly more effective than placebo, and apalutamide emerged as the best option (P score: 0.8809). Apalutamide [hazard ratio (HR): 0.85, 95% credible interval (CrI): 0.77-0.94] and enzalutamide (HR: 0.86, 95% CrI: 0.78-0.95) were both significantly more effective than darolutamide. For PSA-PFS, all three agents were statistically superior to placebo, and apalutamide emerged as the likely preferred option (P score: 1.000). Apalutamide (HR: 0.71, 95% CrI: 0.69-0.74) and enzalutamide (HR: 0.76, 95% CrI: 0.74-0.79) were both significantly more effective than darolutamide. For AEs (including all AEs, grade 3 or grade 4 AEs, grade 5 AEs, and discontinuation rates), darolutamide was the likely best option. Apalutamide and enzalutamide appear to be more efficacious agents for therapy of nmCRPC, while darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials.
Topics: Androgen Receptor Antagonists; Antineoplastic Agents; Benzamides; Humans; Kallikreins; Male; Network Meta-Analysis; Nitriles; Phenylthiohydantoin; Progression-Free Survival; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Pyrazoles; Thiohydantoins; Treatment Outcome
PubMed: 32924096
DOI: 10.1007/s10147-020-01777-9 -
Wiener Klinische Wochenschrift Aug 2020The aim of this systematic review is to provide an update on the effects of resistance exercise (RE) in patients with prostate cancer (PCa), with special attention to...
PURPOSE
The aim of this systematic review is to provide an update on the effects of resistance exercise (RE) in patients with prostate cancer (PCa), with special attention to the effects on sexual health.
METHODS
A systematic search of the literature was conducted in March 2020 using the databases PubMed, MEDLINE, EMBASE, SCOPUS and the Cochrane Library. Only randomized, controlled trials published after 31 December 2016 were included in this update. Additionally, articles from current and previous reviews were utilized to provide a brief summary of the effects on sexual health.
RESULTS
A total of 10 articles met the inclusion criteria, of which 5 were identified as independent studies. The remaining five articles presented additional data for studies, which have already been included. The identified studies further strengthened the evidence for positive effects on muscle strength, body composition and physical function. Positive effects on bone mineral density were apparent only when RE was combined with impact training. One article reported an improvement in fatigue and health-related quality of life. Only one study examined the effects of RE in isolation and three articles indicated positive effects of exercise on sexual health.
CONCLUSION
Recent evidence supports the use of RE in PCa patient rehabilitation as a countermeasure for treatment side effects. Further research is necessary to ascertain the optimal delivery methods and illuminate the effects on health-related quality of life (HRQOL), fatigue and sexual health.
Topics: Androgen Antagonists; Exercise; Exercise Therapy; Hand Strength; Humans; Male; Postural Balance; Prostatic Neoplasms; Quality of Life; Resistance Training; Time and Motion Studies
PubMed: 32681360
DOI: 10.1007/s00508-020-01713-x -
European Urology Sep 2020
Meta-Analysis
Topics: Adverse Drug Reaction Reporting Systems; Androgen Antagonists; Fatigue; Humans; Male; Prostatic Neoplasms
PubMed: 32636097
DOI: 10.1016/j.eururo.2020.06.052 -
Journal of Clinical Oncology : Official... Sep 2020In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been... (Meta-Analysis)
Meta-Analysis
PURPOSE
In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT.
MATERIALS AND METHODS
A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS). Standard fixed-effects meta-analyses were performed for each comparison, and a meta-regression was conducted to adjust for use and duration of ADT. Network meta-analyses were performed to compare EBRT plus ADT versus EBRT plus BT. Bayesian analyses were also performed, and a rank was assigned to each treatment after Markov Chain Monte Carlo analyses to create a surface under the cumulative ranking curve.
RESULTS
Six trials compared EBRT with or without ADT (n = 4,663), and 3 compared EBRT with or without BT (n = 718). The addition of ADT to EBRT improved OS (hazard ratio [HR], 0.71 [95% CI, 0.62 to 0.81]), whereas the addition of BT did not significantly improve OS (HR, 1.03 [95% CI, 0.78 to 1.36]). In a network meta-analysis, EBRT plus ADT had improved OS compared with EBRT plus BT (HR, 0.68 [95% CI, 0.52 to 0.89]). Bayesian modeling demonstrated an 88% probability that EBRT plus ADT resulted in superior OS compared with EBRT plus BT.
CONCLUSION
Our findings suggest that current practice patterns of omitting ADT with EBRT plus BT may result in inferior OS compared with EBRT plus ADT in men with intermediate- and high-risk prostate cancer. ADT for these men should remain a critical component of treatment regardless of radiotherapy delivery method until randomized evidence demonstrates otherwise.
Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Brachytherapy; Chemoradiotherapy; Humans; Male; Network Meta-Analysis; Prostatic Neoplasms; Radiation Dosage; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 32396488
DOI: 10.1200/JCO.19.03217 -
World Journal of Diabetes Mar 2020Transgender individuals receiving masculinising or feminising gender-affirming hormone therapy with testosterone or estradiol respectively, are at increased risk of...
BACKGROUND
Transgender individuals receiving masculinising or feminising gender-affirming hormone therapy with testosterone or estradiol respectively, are at increased risk of adverse cardiovascular outcomes, including myocardial infarction and stroke. This may be related to the effects of testosterone or estradiol therapy on body composition, fat distribution, and insulin resistance but the effect of gender-affirming hormone therapy on these cardiovascular risk factors has not been extensively examined.
AIM
To evaluate the impact of gender-affirming hormone therapy on body composition and insulin resistance in transgender individuals, to guide clinicians in minimising cardiovascular risk.
METHODS
We performed a review of the literature based on PRISMA guidelines. MEDLINE, Embase and PsycINFO databases were searched for studies examining body composition, insulin resistance or body fat distribution in transgender individuals aged over 18 years on established gender-affirming hormone therapy. Studies were selected for full-text analysis if they investigated transgender individuals on any type of gender-affirming hormone therapy and reported effects on lean mass, fat mass or insulin resistance.
RESULTS
The search strategy identified 221 studies. After exclusion of studies that did not meet inclusion criteria, 26 were included (2 cross-sectional, 21 prospective-uncontrolled and 3 prospective-controlled). Evidence in transgender men suggests that testosterone therapy increases lean mass, decreases fat mass and has no impact on insulin resistance. Evidence in transgender women suggests that feminising hormone therapy (estradiol, with or without anti-androgen agents) decreases lean mass, increases fat mass, and may worsen insulin resistance. Changes to body composition were consistent across almost all studies: Transgender men on testosterone gained lean mass and lost fat mass, and transgender women on oestrogen experienced the reverse. No study directly contradicted these trends, though several small studies of short duration reported no changes. Results for insulin resistance are less consistent and uncertain. There is a paucity of prospective controlled research, and existing prospective evidence is limited by small sample sizes, short follow up periods, and young cohorts of participants.
CONCLUSION
Further research is required to further characterise the impact of gender-affirming hormone therapy on body composition and insulin resistance in the medium-long term. Until further evidence is available, clinicians should aim to minimise risk by monitoring cardiovascular risk markers regularly in their patients and encouraging healthy lifestyle modifications.
PubMed: 32180895
DOI: 10.4239/wjd.v11.i3.66 -
Medicine Mar 2020Several studies have tested the addition of adjuvant radiotherapy (RT) to androgen deprivation therapy (ADT) in node-positive prostate cancer (PCa) after radical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several studies have tested the addition of adjuvant radiotherapy (RT) to androgen deprivation therapy (ADT) in node-positive prostate cancer (PCa) after radical prostatectomy (RP). This meta-analysis aims to assess the effects of adding RT to ADT in the treatment of PCa patients with lymph node invasion.
METHODS
We systematically searched PubMed and Embase through June 2018 for human studies comparing RT plus ADT versus ADT in men with node-positive PCa after RP. The primary end point was overall survival (OS). Secondary end point was cancer-specific survival (CSS). Hazard ratios (HRs) with 95% confidence intervals (CIs) for the effects of RT plus ADT on OS and CSS were combined across studies using meta-analysis.
RESULTS
Five studies were selected for inclusion. Overall, 15,524 patients were enrolled in the 5 studies. This included 6309 (40.6%) patients receiving ADT, 4389 (28.3%) patients receiving adjuvant RT plus ADT, and 4826 (31.1%) patients receiving observation. In lymph node-positive PCa patients, the addition of adjuvant RT was associated with improved OS (HR: 0.74; 95% CI, 0.59-0.92; P = .008). Moreover, the addition of adjuvant RT was also associated with a dramatic CSS improvement (HR: 0.40; 95% CI, 0.27-0.59; P = .000).
CONCLUSIONS
Adding RT to ADT may be a clinically effective treatment option for men with lymph node-positive PCa after RP.
Topics: Aged; Aged, 80 and over; Androgen Antagonists; Combined Modality Therapy; Humans; Lymphatic Metastasis; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Adjuvant; Survival Analysis; Treatment Outcome
PubMed: 32150055
DOI: 10.1097/MD.0000000000019153 -
Prostate Cancer and Prostatic Diseases Sep 2020The androgen receptor (AR) is a key prostate cancer drug target. Suppression of AR signaling mediated by the full-length AR (AR-FL) is the therapeutic goal of all...
BACKGROUND
The androgen receptor (AR) is a key prostate cancer drug target. Suppression of AR signaling mediated by the full-length AR (AR-FL) is the therapeutic goal of all existing AR-directed therapies. AR-targeting agents impart therapeutic benefit, but lead to AR aberrations that underlie disease progression and therapeutic resistance. Among the AR aberrations specific to castration-resistant prostate cancer (CRPC), AR variants (AR-Vs) have emerged as important indicators of disease progression and therapeutic resistance.
METHODS
We conducted a systemic review of the literature focusing on recent laboratory studies on AR-Vs following our last review article published in 2016. Topics ranged from measurement and detection, molecular origin, regulation, genomic function, and preclinical therapeutic targeting of AR-Vs. We provide expert opinions and perspectives on these topics.
RESULTS
Transcript sequences for 22 AR-Vs have been reported in the literature. Different AR-Vs may arise through different mechanisms, and can be regulated by splicing factors and dictated by genomic rearrangements, but a low-androgen environment is a prerequisite for generation of AR-Vs. The unique transcript structures allowed development of in situ and in-solution measurement and detection methods, including mRNA and protein detection, in both tissue and blood specimens. AR-V7 remains the main measurement target and the most extensively characterized AR-V. Although AR-V7 coexists with AR-FL, genomic functions mediated by AR-V7 do not require the presence of AR-FL. The distinct cistromes and transcriptional programs directed by AR-V7 and their coregulators are consistent with genomic features of progressive disease in a low-androgen environment. Preclinical development of AR-V-directed agents currently focuses on suppression of mRNA expression and protein degradation as well as targeting of the amino-terminal domain.
CONCLUSIONS
Current literature continues to support AR-Vs as biomarkers and therapeutic targets in prostate cancer. Laboratory investigations reveal both challenges and opportunities in targeting AR-Vs to overcome resistance to current AR-directed therapies.
Topics: Alternative Splicing; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Clinical Decision-Making; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Genetic Testing; Humans; Male; Precision Medicine; Progression-Free Survival; Prostatic Neoplasms, Castration-Resistant; Protein Isoforms; Proteolysis; Receptors, Androgen; Transcriptional Activation
PubMed: 32139878
DOI: 10.1038/s41391-020-0217-3 -
Quality of Life Research : An... Apr 2020The aim of this review is to systematically review randomized controlled trials on lifestyle interventions on PCa patients undergoing androgen deprivation therapy.
PURPOSE
The aim of this review is to systematically review randomized controlled trials on lifestyle interventions on PCa patients undergoing androgen deprivation therapy.
METHODS
A literature search was conducted using the electronic databases Medline and PubMed. To be eligible, studies had to be randomized controlled trials (RCTs) that focused on side effects of ADT and lifestyle interventions to reduce side effects for men undergoing ADT with PCa. Lifestyle interventions were defined as interventions that included any dietary or behavioral components.
RESULTS
Twenty-nine trials were included. Most of them focused on exercise interventions, while some investigated the effect of dietary or behavioral interventions. The effect of different lifestyle influencing modalities aimed to improve on the adverse effects of ADT varied greatly.
CONCLUSIONS
It is not possible to draw one conclusion on the effect of exercise-based interventions, but noted on several adverse effects of ADT improvement. Further studies are necessary to develop personalized lifestyle interventions in order to mitigate the adverse effects.
Topics: Aged; Androgen Antagonists; Diet; Diet Therapy; Drug-Related Side Effects and Adverse Reactions; Exercise Therapy; Humans; Life Style; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 31832978
DOI: 10.1007/s11136-019-02361-z