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Urologic Oncology Sep 2024The influence of androgen suppression therapy (AST) on bladder cancer (BCa) remains controversial, as recent studies have not reached a consensus regarding the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The influence of androgen suppression therapy (AST) on bladder cancer (BCa) remains controversial, as recent studies have not reached a consensus regarding the relationship between AST and the incidence or prognosis of BCa.
MATERIALS AND METHODS
We perform an updated systematic review and meta-analysis utilizing the most recent evidence to investigate the potential influence of AST on the incidence and prognosis of BCa. A comprehensive literature search was performed on the PubMed, Medline, Embase, Web of Science, and the Cochrane Library databases to include potentially eligible studies. Hazard ratios (HR) and odds ratios (OR) were used to calculate the incidence and prognosis of BCa.
RESULTS
This meta-analysis included 22 studies with 700,755 participants which investigated the impact of AST on the risk and prognosis of BCa. The pooled results revealed no significant relation between AST and a decreased incidence of BCa (OR: 0.92, 95%CI: 0.77-1.09, P = 0.342). Subgroup analysis reported that patients receiving 5-alpha reductase inhibitors (5-ARIs) exhibited a significantly lower risk of BCa (OR: 0.83, 95%CI: 0.75-0.91, P < 0.001), while androgen deprivation therapy did not show a significant reduction (OR: 1.00, 95%CI: 0.46-2.16, P = 0.995). AST may also significantly improve the recurrence-free survival of patients with BCa (HR: 0.69, 95%CI: 0.50-0.95, P = 0.023). We also detected a significant improvement in OS among BCa patients who received 5-ARIs compared to those without 5-ARIs (HR: 0.82, 95%CI: 0.68-0.99, P = 0.037).
CONCLUSION
No significant correlation was found between AST and a decreased BCa incidence, while 5-ARIs have demonstrated efficacy in reducing BCa occurrence. Moreover, patients who received AST demonstrated improved prognosis.
Topics: Humans; Urinary Bladder Neoplasms; Androgen Antagonists; Incidence; Prognosis; Male
PubMed: 38729866
DOI: 10.1016/j.urolonc.2024.04.014 -
European Urology Oncology Apr 2024It remains unclear to what extent the therapy of the primary local tumor, such as radical prostatectomy (RP) and radiation therapy (RT), improves overall survival in... (Review)
Review
CONTEXT
It remains unclear to what extent the therapy of the primary local tumor, such as radical prostatectomy (RP) and radiation therapy (RT), improves overall survival in patients with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). However, data suggest a benefit of these therapies in preventing local events secondary to local tumor progression.
OBJECTIVE
To evaluate the efficacy of adding local therapy (RP or RT) to systemic therapies, including androgen deprivation therapy, docetaxel, and/or androgen receptor axis-targeted agents, in preventing local events in mHSPC patients compared with systemic therapy alone (ie, without RT of the prostate or RP).
EVIDENCE ACQUISITION
Three databases and meeting abstracts were queried in November 2023 for studies analyzing mHSPC patients treated with local therapy. The primary outcome of interest was the prevention of overall local events (urinary tract infection, urinary tract obstruction, and gross hematuria) due to local disease progression. Subgroup analyses were conducted to assess the differential outcomes according to the type of local therapy (RP or RT).
EVIDENCE SYNTHESIS
Overall, six studies, comprising two randomized controlled trials, were included for a systematic review and meta-analysis. The overall incidence of local events was significantly lower in the local treatment plus systemic therapy group than in the systemic therapy only groups (relative risk [RR]: 0.50, 95% confidence interval [CI]: 0.28-0.88, p = 0.016). RP significantly reduced the incidence of overall local events (RR: 0.24, 95% CI: 0.11-0.52) and that of local events requiring surgical intervention (RR: 0.08, 95% CI: 0.03-0.25). Although there was no statistically significant difference between the RT plus systemic therapy and systemic therapy only groups in terms of overall local events, the incidence of local events requiring surgical intervention was significantly lower in the RT plus systemic therapy group (RR: 0.70, 95% CI: 0.49-0.99); local events requiring surgical intervention of the upper urinary tract was significantly lower in local treatment groups (RR: 0.60, 95% CI: 0.37-0.98, p = 0.04). However, a subgroup analysis revealed that neither RP nor RT significantly impacted the prevention of local events requiring surgical intervention of the upper urinary tract.
CONCLUSIONS
In some patients with mHSPC, RP or RT of primary tumor seems to reduce the incidence of local progression and events requiring surgical intervention. Identifying which patients are most likely to benefit from local therapy, and at what time point (eg, after response of metastases), will be necessary to set up a study assessing the risk, benefits, and alternatives to therapy of the primary tumor in the mHSPC setting.
PATIENT SUMMARY
Our study suggests that local therapy of the prostate, such as radical prostatectomy or radiotherapy, in patients with metastatic hormone-sensitive prostate cancer can prevent local events, such as urinary obstruction and gross hematuria.
PubMed: 38575408
DOI: 10.1016/j.euo.2024.03.007 -
Urologia Nov 2023Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and... (Review)
Review
Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and penis are diagnosed early and treated in relatively younger patients in which couple fertility can be an important concern. The purpose of this review is to highlight both the pathogenetic mechanisms of damage to male fertility in the context of the main urological cancers and the methods of preserving male fertility in an oncological setting, in light of the most recent scientific evidence. A systematic review of available literature was carried out on the main scientific search engines, such as PubMed, Clinicaltrials.Gov, and Google scholar. Three hundred twenty-five relevant articles on this subject were identified, 98 of which were selected being the most relevant to the purpose of this review. There is a strong evidence in literature that all of the genitourinary oncological therapies have a deep negative impact on male fertility: orchiectomy, partial orchiectomy, retroperitoneal lymphadenectomy (RPLND), radical cystectomy, prostatectomy, penectomy, as well as radiotherapy, chemotherapy, and hormonal androgen suppression. Preservation of fertility is possible and includes cryopreservation, hormonal manipulation with GnRH analogs before chemotherapy, androgen replacement. Germ cell auto transplantation is an intriguing strategy with future perspectives. Careful evaluation of male fertility must be a key point before treating genitourinary tumors, taking into account patients' age and couples' perspectives. Informed consent should provide adequate information to the patient about the current state of his fertility and about the balance between risks and benefits in oncological terms. Standard approaches to genitourinary tumors should include a multidisciplinary team with urologists, oncologists, radiotherapists, psycho-sexologists, andrologists, gynecologists, and reproductive endocrinologists.
Topics: Humans; Male; Fertility Preservation; Androgens; Infertility, Male; Testicular Neoplasms; Urologic Neoplasms
PubMed: 37491831
DOI: 10.1177/03915603221146147 -
Progres En Urologie : Journal de... May 2023Prostate cancer is a frequent disease and one of the main treatments used is androgen deprivation therapy, which is a therapy with disabling side effects....
AIM
Prostate cancer is a frequent disease and one of the main treatments used is androgen deprivation therapy, which is a therapy with disabling side effects. Non-pharmacological interventions (NPIs) are evidenced based, non-invasive interventions on human health. They are classified into five categories (physical, psychological, nutritional, digital, elemental). The NPIs sphere is booming and still remains underused in this context.
METHODS
A systematic review concerning randomized controlled trials was executed according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We used the "Medline" and "Kalya Research" databases. After searching and selecting eligible publications, we included 37 randomized controlled trials.
RESULTS
The majority of articles concerned physical NPIs with 30 clinical studies, 3 publications dealt with nutritional NPIs, 2 with psychological NPIs and 2 articles concerned elemental NPIs. No publication about digital NPI was found. All of the studies aimed to manage and improve the side effects of treatment. No elemental NPI has demonstrated benefit. Only one psychological NPI and one nutritional NPI were effective. Five types of physical NPI protocols have shown efficacy. The main benefits related to physical abilities, body composition, osteoporosis, quality of life, fatigue, reduced cardiovascular risk and finally anxiety and depression.
CONCLUSION
Non-pharmacological interventions, especially physical ones, are effective in managing and reducing the side effects associated with androgen deprivation therapy and should be offered to patients in this context.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Androgens; Quality of Life; Physical Examination
PubMed: 37121810
DOI: 10.1016/j.purol.2023.03.005 -
Journal of Cancer Research and Clinical... Aug 2023The newly published ARASENS trial has demonstrated the clinical efficacy of darolutamide for metastatic hormone-sensitive prostate cancer (mHSPC). However, the use of... (Meta-Analysis)
Meta-Analysis
Based on ARASENS trial: efficacy and safety of darolutamide as an emerging option of endocrinotherapy for metastatic hormone-sensitive prostate cancer-an updated systematic review and network meta-analysis.
PURPOSE
The newly published ARASENS trial has demonstrated the clinical efficacy of darolutamide for metastatic hormone-sensitive prostate cancer (mHSPC). However, the use of darolutamide as the latest first-line androgen receptor pathway inhibitor for mHSPC has not been compared with other androgen receptor targeted agents (ARTAs). Given the lack of head-to-head randomized trials, we performed this updated meta-analysis to conduct indirect comparison for the efficacy and safety of darolutamide with other new-generation ARTAs.
METHODS
By searching the databases of PubMed, Scopus, Cochrane Library, and Embase, 9 large randomized controlled trials evaluating ARTAs for mHSPC patients were eventually screened according to PRISMA. We extracted data from overall survival, castration-resistant progression, and adverse events for network meta-analysis using the Bayesian and standard frequentist models.
RESULTS
Darolutamide combination emerged with superiority (HR = 0.68, 95%CrI = 0.57-0.81) among four androgen receptor inhibitors for patients with high Gleason score (HR = 0.71, 95%CrI = 0.59-0.86). Darolutamide was best tolerated in several androgen suppression-related adverse events (AEs).
CONCLUSION
Darolutamide appears to be an optional androgen receptor inhibitor for mHSPC patients, especially for patients with Gleason score ≥ 8. Its well-tolerated characteristic may provide a preferred drug option for patients with poor cardiovascular function and bone health.
Topics: Male; Humans; Receptors, Androgen; Prostatic Neoplasms, Castration-Resistant; Network Meta-Analysis; Bayes Theorem; Androgen Receptor Antagonists; Hormones; Androgen Antagonists; Randomized Controlled Trials as Topic
PubMed: 36856851
DOI: 10.1007/s00432-023-04658-6 -
The Aging Male : the Official Journal... Dec 2022The aim of the meta-analysis was to explore effects of resistance exercise (RE) on body composition and physical function in patients with prostate cancer (PCa). (Meta-Analysis)
Meta-Analysis
The effects of resistance exercise on body composition and physical function in prostate cancer patients undergoing androgen deprivation therapy: an update systematic review and meta-analysis.
OBJECTIVE
The aim of the meta-analysis was to explore effects of resistance exercise (RE) on body composition and physical function in patients with prostate cancer (PCa).
DATA SOURCES
We searched the electronic databases of Pubmed, Embase, Cochrane, and web of science. Published studies have been collected from these databases. Search terms include RE PCa, with a deadline of 31 March 2022.
MAIN RESULTS
These studies showed significant improvements of body composition(Lean body mass MD: 1.12 95% CI [0.48, 1.76], < 0.01; Body fat rate MD: -1.12 95% CI [-1.99,-0.24], < 0.05; Appendicular skeletal mass MD: 0.74 95% CI [0.45, 1.03], < 0.01) and physical function (leg press MD: 77.95 95% CI [38.90, 117.00], < 0.01; stair climb MD:-0.30 95% CI [-0.49, -0.12], < 0.01). In addition, the improvement of Body fat mass (MD: -0.21 95% CI [-0.79, 0.37], > 0.05), 400 m walk (MD: -21.74 95% CI [-45.53, 2.05], > 0.05) and times up and go (MD: -0.50 95% CI [-1.03, 0.03], > 0.05) were not obvious. Subgroup analyses showed that RE for ≥ 6 months (compared with RE intervention for < 6 months) and starting exercise immediately after androgen deprivation therapy (ADT) (compared with delayed exercise after ADT) resulted in more significant improvements in body composition. Furthermore, the results showed that the exercise intensity of 8-12 RM significantly improved body composition.
CONCLUSIONS
RE seems to be a promising approach in order to improve body composition and physical function in PCa patients to offset their treatment-related side effects. RE should be used as a means of rehabilitation and care for PCa. Starting exercise immediately after ADT and extending exercise time while choosing the right intensity can better improve the patients' body composition and function.
REGISTRATION NUMBER
INPLASY202280019.
Topics: Male; Humans; Androgen Antagonists; Resistance Training; Prostatic Neoplasms; Androgens; Body Composition; Exercise Therapy
PubMed: 36382930
DOI: 10.1080/13685538.2022.2146670 -
Scandinavian Journal of Pain Jul 2022Opioid analgesics are the main stay for cancer pain management; however, long-term opioid treatment (L-TOT) may suppress the endocrine system. This systemic review aimed...
OBJECTIVES
Opioid analgesics are the main stay for cancer pain management; however, long-term opioid treatment (L-TOT) may suppress the endocrine system. This systemic review aimed at investigating effects of L-TOT on the endocrine system in patients with cancer-related pain.
METHODS
A search on MEDLINE, EMBASE and Web of Science databases was performed. Inclusion criteria were clinical studies investigating endocrine measures in adult patients with cancer-related pain in L-TOT (≥4 weeks). Outcomes and quality of evidence were assessed.
RESULTS
A total of 252 abstracts were identified; out of which 247 were excluded and five cross-sectional studies were included and analyzed. L-TOT was associated with lower serum concentration levels of total- and free testosterone in males, follicular stimulating hormone in females, and luteinizing hormone in both sexes. Moreover, higher morphine equivalent daily doses (MEDDs) were correlated with higher levels of cortisol and lower levels of LH in both sexes, and lower levels of total- and free testosterone in males. Sexual dysfunction was associated with low sex hormone levels. Level of evidence was low/very low.
CONCLUSIONS
The studies identified demonstrated that patients with cancer-related pain in L-TOT may have gonadal hypofunction causing sexual dysfunction, which may be correlated with opioid dose level. In addition, high serum concentrations of cortisol were positively correlated with high opioid dose levels. However, the evidence was weak and further research is necessary. PROSPERO, ID-number: CRD42020213059.
Topics: Adult; Analgesics, Opioid; Cancer Pain; Cross-Sectional Studies; Endocrine System; Female; Humans; Hydrocortisone; Male; Neoplasms; Sexual Dysfunction, Physiological; Testosterone
PubMed: 35316595
DOI: 10.1515/sjpain-2021-0196 -
Frontiers in Oncology 2021The purpose of this study was to summarize the existing evidence and develop a comprehensive systematic review of the impact of androgen suppression therapy (AST) on the...
PURPOSE
The purpose of this study was to summarize the existing evidence and develop a comprehensive systematic review of the impact of androgen suppression therapy (AST) on the incidence or clinical outcomes of bladder cancer.
METHODS
We systematically searched the PubMed and Embase databases from inception to June 20, 2021 to identify all observational studies examining the incidence or clinical outcomes of bladder cancer in patients who received AST. AST is defined as the use of 5-alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT).
RESULTS
A total of 18 observational studies were included. Our results showed that AST was not significantly associated with a reduced risk of BCa incidence (OR: 0.92, 95% CI: 0.68-1.24) compared with the lack of AST. The subgroup analysis revealed that finasteride use was significantly associated with a reduction in the risk of BCa incidence (OR: 0.75, 95% CI: 0.64-0.88). Recurrence-free survival (RFS) was improved among AST users compared with nonusers (HR: 0.68, 95% CI: 0.48-0.95), while no significant difference between AST users versus nonusers was identified for cancer-specific survival (CSS), overall survival (OS) or progression-free survival (PFS).
CONCLUSION
Current evidence indicates that therapy with finasteride may represent a potential strategy aimed at reducing BCa incidence. Moreover, AST has a beneficial effect on the recurrence of bladder cancer. Further well-designed randomized trials or cohort studies with better characterized study populations are needed to validate our preliminary findings.
SYSTEMATIC REVIEW REGISTRATION
International Prospective Register of Systematic Reviews database [https://www.crd.york.ac.uk/PROSPERO/], identifier CRD42021261685.
PubMed: 34970495
DOI: 10.3389/fonc.2021.784627 -
Andrology Mar 2022Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with several side effects, including negative feedback of the hypothalamic-pituitary-gonadal axis, resulting in suppression of intratesticular testosterone production and spermatogenesis. To preserve these testicular functions while treating male hypogonadism, clomiphene citrate is used as off-label therapy. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of clomiphene citrate therapy for men with hypogonadism.
METHODS
The EMBASE, PubMed, Cochrane databases were searched in May 2021, for effectiveness studies of men with hypogonadism treated with clomiphene citrate. Both intervention and observational studies were included. The Effective Public Health Practice Project Quality Assessment Tool, a validated instrument, was used to assess methodological study quality. The primary outcome measure was the evaluation of serum hormone concentration. Secondary outcomes were symptoms of hypogonadism, metabolic and lipid profile, side effects, safety aspects.
RESULTS
We included 19 studies, comprising four randomized controlled trials and 15 observational studies, resulting in 1642 patients. Seventeen studies were included in the meta-analysis, with a total of 1279 patients. Therapy and follow-up duration varied between one and a half and 52 months. Total testosterone increased with 2.60 (95% CI 1.82-3.38) during clomiphene citrate treatment. An increase was also seen in free testosterone, luteinizing hormone, follicle stimulating hormone, sex hormone-binding globulin and estradiol. Different symptom scoring methods were used in the included studies. The most frequently used instrument was the Androgen Deficiency in Aging Males questionnaire, whose improved during treatment. Reported side effects were only prevalent in less than 10% of the study populations and no serious adverse events were reported.
CONCLUSION
Clomiphene citrate is an effective therapy for improving both biochemical as well as clinical symptoms of males suffering from hypogonadism. Clomiphene citrate has few reported side effects and good safety aspects.
Topics: Clomiphene; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Testosterone
PubMed: 34933414
DOI: 10.1111/andr.13146 -
Gan To Kagaku Ryoho. Cancer &... Dec 2021In Japan, the incidence of prostate cancer(Pca)has been increasing mainly due to the early detection system by PSA screening. Considering pharmacoepidemiology, the... (Meta-Analysis)
Meta-Analysis
In Japan, the incidence of prostate cancer(Pca)has been increasing mainly due to the early detection system by PSA screening. Considering pharmacoepidemiology, the statins and metformin have been recognized to lower the risk of incidence of Pca. Excessive intake of calcium, multivitamin and vitamin E increased the Pca risk. The 5-alpha-reductase inhibitors( 5ARIs)are widely used in the treatment of benign prostatic hyperplasia(BPH)by biological function of inhibiting the conversion from testosterone to dihydrotestosterone. A systematic review and meta-analysis identified that 5ARIs had no impact on overall mortality and Pca-related mortality, nor on high-grade Pca diagnosis. The use of anti-hypertensive drugs was reportedly associated with an increasing risk of Pca. However, as an effect of post diagnostic use of anti-hypertensive drugs, angiotensin Ⅱ receptor blockers(ARBs)was associated with improved overall survival and cause specific survival, which means the second chemoprevention potential for Pca. Our previous investigation demonstrated ARBs can suppress the expression of androgen receptor and affect the proliferative signal transduction system in Pca cells. Based on additional data of our experiment, we confirmed the anti-tumor effect of ARBs for Pca, and further clinical trials to make sure the chemoprevention for pre-diagnostic Pca is needed in future.
Topics: 5-alpha Reductase Inhibitors; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chemoprevention; Humans; Male; Prostatic Neoplasms
PubMed: 34911906
DOI: No ID Found