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European Urology Oncology Feb 2024Since 2015 there have been major advances in the management of primary metastatic hormone-sensitive prostate cancer (mHSPC) following the publication of key clinical... (Review)
Review
Does Research from Clinical Trials in Metastatic Hormone-sensitive Prostate Cancer Treatment Translate into Access to Treatments for Patients in the "Real World"? A Systematic Review.
CONTEXT
Since 2015 there have been major advances in the management of primary metastatic hormone-sensitive prostate cancer (mHSPC) following the publication of key clinical trials that demonstrated significant clinical benefits with docetaxel chemotherapy or novel hormone therapy (NHT) in addition to androgen deprivation therapy (ADT). Despite these advances, there is evidence to show that these treatments are not being utilised for mHSPC in clinical practice.
OBJECTIVE
To determine the utilisation of docetaxel and NHT in mHSPC in routine practice and the determinants of variation in their use.
EVIDENCE ACQUISITION
MEDLINE and Embase were searched systematically for studies on utilisation of treatments for primary mHSPC that were based on regional or national data sets and published after January 2005. Study results were summarised using a narrative synthesis.
EVIDENCE SYNTHESIS
Thirteen papers were included in the analysis, six full-text articles and seven abstracts, on studies that included a total of 166 876 patients. The utilisation rate of treatment intensification with either docetaxel or NHT (enzalutamide, apalutamide, or abiraterone) in addition to ADT ranged from 9.3% to 38.1% across the studies. Younger, White patients with fewer comorbidities and living in more urban settings were more likely to be prescribed treatment intensification. Patients treated in private academic institutions by oncologists were more likely to receive docetaxel or NHT. Socioeconomic status did not impact receipt of systemic therapy. NHT utilisation rates appear to have increased over time.
CONCLUSIONS
These results highlight the need to change the approach to the treatment of primary mHSPC in the real world by harnessing the practice-changing results from recent trials in this setting to optimise upfront systemic therapy for this patient population.
PATIENT SUMMARY
We reviewed the use of treatments for primary metastatic hormone-sensitive prostate cancer that showed a benefit in key clinical trials. We found that these treatments are underused, particularly among certain patient groups.
Topics: Male; Humans; Prostatic Neoplasms; Docetaxel; Androgen Antagonists; Treatment Outcome; Hormones; Health Services Accessibility
PubMed: 37380578
DOI: 10.1016/j.euo.2023.05.002 -
Archivio Italiano Di Urologia,... Dec 2021Serenoa repens (SR) is a plant used to treat benign prostatic hyperplasia and prostatitis. We know that SR act as a 5α-reductase inhibitor, moreover, several studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Serenoa repens (SR) is a plant used to treat benign prostatic hyperplasia and prostatitis. We know that SR act as a 5α-reductase inhibitor, moreover, several studies have proved that SR has anti-inflammatory and antioxidant properties. There is some belief among patients that SR may negatively impact male sexual function. Such belief is circulating in non-medical social networks and is perhaps maintained by patients as a result of incorrect web surfing. However, it is also possible that SR may exert a "nocebo" effect thus negatively impacting on the general well-being of patients.
OBJECTIVE
The aim of this study is to investigate whether SR is causing negative effects on male sexual function.
METHODS
To ascertain the effect of SR on male sexual function, we conducted a systematic review and meta-analysis, by performing an electronic database search in accordance with the PRISMA guidelines.
RESULTS
Out of 20 included papers, 8 papers reported comparisons of SR with placebo, and 7 studies reported comparisons of SR with tamsulosin. The standardized mean difference of changes from baseline scores of sexual function was not significantly different between SR and placebo (SMD: 0.43, 95% CI: 0.18 to 1.05; I^2 = 95%). Similarly, no significant mean differences in the Male Sexual Function-4 (MSF-4) test scores were found between SR and tamsulosin (SMD: -0.31, 95% CI: -0.82 to 0.19; I^2 = 90%).
CONCLUSIONS
We found no statistically significant differences between negative effects on sexual function in patients treated with SR compared to patients who received placebo. The results of our meta-analysis are similar to those of other systematic reviews. Studies are warranted to ascertain whether any such effects might occur as a result of a nocebo effect.
Topics: 5-alpha Reductase Inhibitors; Androgen Antagonists; Humans; Male; Plant Extracts; Prostatic Hyperplasia; Randomized Controlled Trials as Topic; Serenoa; Tamsulosin
PubMed: 34933534
DOI: 10.4081/aiua.2021.4.475 -
Journal of Clinical Oncology : Official... Jan 2021There remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa).... (Meta-Analysis)
Meta-Analysis
PURPOSE
There remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa.
METHODS
MEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS).
RESULTS
The median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% 3%, = .33) or genitourinary toxicity (5% 5%, = .76) between groups.
CONCLUSION
The sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity.
Topics: Androgen Antagonists; Clinical Trials, Phase III as Topic; Humans; Male; Neoadjuvant Therapy; Neoplasm Metastasis; Prostatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 33275486
DOI: 10.1200/JCO.20.02438 -
Current Opinion in Urology Jan 2022To investigate the features and optimal management of pN+ cM0 prostate cancer (PCa) according to registry-based studies.
PURPOSE OF REVIEW
To investigate the features and optimal management of pN+ cM0 prostate cancer (PCa) according to registry-based studies.
RECENT FINDINGS
Up to 15% of PCa patients harbor lymph node invasion (pN+) at radical prostatectomy plus lymph node dissection. Nonetheless, the optimal management strategy in this setting is not well characterized.
SUMMARY
We performed a systematic review including n = 13 studies. Management strategies comprised 13 536 men undergoing observation, 11 149 adjuvant androgen deprivation therapy (aADT), 7,075 adjuvant radiotherapy (aRT) +aADT and 705 aRT. Baseline features showed aggressive PCa in the majority of men. At a median follow-up ranging 48-134months, Cancer-related death was 5% and overall-mortality 16.6%. aADT and aRT alone had no cancer-specific survival or overall survival advantages over observation only and over not performing aRT, respectively. aADT plus aRT yielded a survival benefit compared to observation and aADT, which in one study, were limited to certain intermediate-risk categories. Age, Gleason, Charlson score, positive surgical margins, pathological stage, and positive nodes number, but not prostate specific antigen, were most relevant prognostic factors. Our work further confirmed pN+ PCa is a multifaceted disease and will help future research in defining its optimal management based on different risk categories to maximize survival and patient's quality of life.
Topics: Androgen Antagonists; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Quality of Life; Radiotherapy, Adjuvant; Retrospective Studies
PubMed: 34812201
DOI: 10.1097/MOU.0000000000000946 -
JACC. CardioOncology Oct 2023Androgen deprivation therapy is the cornerstone of treatment for patients with advanced prostate cancer. Meta-analysis of small, oncology-focused trials suggest...
BACKGROUND
Androgen deprivation therapy is the cornerstone of treatment for patients with advanced prostate cancer. Meta-analysis of small, oncology-focused trials suggest gonadotropin-releasing hormone (GnRH) antagonists may be associated with fewer adverse cardiovascular outcomes compared with GnRH agonists.
OBJECTIVES
This study sought to determine whether GnRH antagonists were associated with fewer major adverse cardiovascular events compared with GnRH agonists.
METHODS
Electronic databases were searched for all prospective, randomized trials comparing GnRH antagonists with agonists. The primary outcome was a major adverse cardiovascular event as defined by the following standardized Medical Dictionary for Regulatory Activities terms: "myocardial infarction," "central nervous system hemorrhages and cerebrovascular conditions," and all-cause mortality. Bayesian meta-analysis models with random effects were fitted.
RESULTS
A total of 11 eligible studies of a maximum duration of 3 to 36 months (median = 12 months) enrolling 4,248 participants were included. Only 1 trial used a blinded, adjudicated event process, whereas potential bias persisted in all trials given their open-label design. A total of 152 patients with primary outcome events were observed, 76 of 2,655 (2.9%) in GnRH antagonist-treated participants and 76 of 1,593 (4.8%) in agonist-treated individuals. Compared with GnRH agonists, the pooled OR of GnRH antagonists for the primary endpoint was 0.57 (95% credible interval: 0.37-0.86) and 0.58 (95% credible interval: 0.32-1.08) for all-cause death.
CONCLUSIONS
Despite the addition of the largest, dedicated cardiovascular outcome trial, the volume and quality of available data to definitively answer this question remain suboptimal. Notwithstanding these limitations, the available data suggest that GnRH antagonists are associated with fewer cardiovascular events, and possibly mortality, compared with GnRH agonists.
PubMed: 37969642
DOI: 10.1016/j.jaccao.2023.05.011 -
Minerva Urology and Nephrology Jun 2022
Meta-Analysis
Comment on: "Androgen receptor axis-targeted agents for non-metastatic castration-resistant prostate cancer impact on overall survival and safety profile: an updated systematic review and meta-analysis".
Topics: Androgen Antagonists; Androgen Receptor Antagonists; Antineoplastic Agents; Humans; Male; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen
PubMed: 35607782
DOI: 10.23736/S2724-6051.22.04948-5 -
Einstein (Sao Paulo, Brazil) 2022To evaluate whether the addition of statins to the new antiandrogens (enzalutamide or abiraterone) affects overall survival in patients with metastatic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate whether the addition of statins to the new antiandrogens (enzalutamide or abiraterone) affects overall survival in patients with metastatic castration-resistant prostate cancer.
METHODS
We searched studies in English language including the keywords statins, overall survival, and metastatic castration-resistant prostate cancer, at PubMed® (MEDLINE®), Embase and Cochrane databases.
RESULTS
A total of 195 articles were initially identified, but only four met the inclusion criteria and were selected for the meta-analysis. A total of 955 patients, 632 on the new antiandrogens only group, and 323 on the new antiandrogens + statins group, were analyzed. In all four studies the combination therapy (new antiandrogens + statin) was well tolerated, regardless of which new antiandrogens were used. Neither the type of statin nor the doses and duration of use were well specified in the studies. The combination therapy in metastatic castration-resistant prostate cancer was associated with an overall survival improvement, and a 46% reduction in death (hazard ratio of 0.54; 95%CI 0.34-0.87; p<0.01) in multivariate analysis.
CONCLUSION
There seems to be a clinical benefit with the association of statins to the new antiandrogens in patients with metastatic castration-resistant prostate cancer, suggesting longer overall survival with no important collateral effect. However, due to fragility of the studies available in the literature, we are not yet capable of recommending this combination of drugs in the clinical practice. Further randomized prospective studies are warranted to confirm these beneficial outcomes.
Topics: Androgen Antagonists; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome
PubMed: 35384986
DOI: 10.31744/einstein_journal/2022RW6339 -
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 -
Frontiers in Endocrinology 2023Orchiectomy has been replaced by medication represented by luteinizing hormone-releasing hormone (LHRH) agonist as the first-line therapy for androgen deprivation...
BACKGROUND
Orchiectomy has been replaced by medication represented by luteinizing hormone-releasing hormone (LHRH) agonist as the first-line therapy for androgen deprivation therapy (ADT). After the wide application of LHRH agonist, the side-effects of long-term ADT were noticed. It is time to reconsider the role of medication and surgeries in the treatment of prostate cancer.
METHODS
Embase, Pubmed, Web of science and Cochrane library were searched for relevant trials. Quality of the studies and risk of bias were assessed by using the Newcastle-Ottawa Scale (NOS). Therapeutic and adverse effects, as well as long-term metabolic adverse effects were extracted from the selected studies. The data synthesized in meta-analyses were performed with R software (4.2.1). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining outcome data including complete and partial response rate, progression rate, death rate and adverse effects such as hot flash and increase in pain. Descriptive analysis was performed among the prostate specific antigen (PSA), testosterone and metabolic adverse effects due to a lack of homogeneity of frailty measures.
RESULTS
1,711 participants from 11 studies were included in our systematic review. 1,258 patients from six studies were included in the meta-analysis. Based on the meta-analysis, the therapeutic and adverse outcomes included overall response rate, complete response rate, partial response rate, stable rate, progression rate, death rate and hot flashes. No statistical significance was observed between LHRH agonists and orchiectomy. Compared with surgery, LHRH agonist elevated the risk of the increase in pain. In descriptive analysis, it was shown that the therapeutic effects between PSA and testosterone also showed no significant difference. Both groups had lipid and glucose metabolic disorders, and a few studies reported worse lipid metabolic performance in orchiectomy group and worse insulin resistance in LHRH agonist group.
CONCLUSION
We found that the therapeutic outcomes were similar between the two options. The results of lipid and glucose metabolic abnormality were controversial in existing studies. The direct comparison studies on metabolic adverse effects should be performed in the future. The therapeutic, metabolic, psychological and economical effects should be considered before applying ADT methods.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022365891.
Topics: Humans; Male; Androgen Antagonists; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Lipids; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone
PubMed: 36814583
DOI: 10.3389/fendo.2023.1131715 -
The Cochrane Database of Systematic... Jun 2021Polycystic ovarian syndrome (PCOS) is characterised by both metabolic and reproductive disorders, and affects 5% to 15% of women of reproductive age. Different western... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovarian syndrome (PCOS) is characterised by both metabolic and reproductive disorders, and affects 5% to 15% of women of reproductive age. Different western medicines have been proposed for PCOS-related subfertility, such as oral contraceptives, insulin sensitisers and laparoscopic ovarian drilling (LOD). Chinese herbal medicines (CHM) have also been used for subfertility caused by PCOS for decades, and are expected to become an alternative treatment for subfertile women with PCOS.
OBJECTIVES
To assess the efficacy and safety of Chinese herbal medicine (CHM) for subfertile women with polycystic ovarian syndrome (PCOS).
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase and six other databases, from inception to 2 June 2020. In addition, we searched three trials registries, the reference lists of included trials and contacted experts in the field to locate trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing CHM versus placebo, no treatment or conventional (western) therapies for the treatment of subfertile women with PCOS.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened trials for inclusion, assessed the risk of bias in included studies and extracted data. We contacted primary study authors for additional information. We conducted meta-analyses. We used the odds ratios (ORs) to report dichotomous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods.
MAIN RESULTS
We included eight RCTs with 609 participants. The comparisons in the included trials were as follows: CHM versus clomiphene, CHM plus clomiphene versus clomiphene (with or without ethinyloestradiol cyproterone acetate (EE/CPA)), CHM plus follicle aspiration plus ovulation induction versus follicle aspiration plus ovulation induction alone, and CHM plus laparoscopic ovarian drilling (LOD) versus LOD alone. The overall certainty of the evidence for most comparisons was very low. None of the included studies reported the primary outcome, live birth rate. Most studies reported the secondary outcomes, and only one study reported data on adverse events. In trials that compared CHM to clomiphene (with or without LOD in both study arms), we are uncertain of the effect of CHM on pregnancy rates (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.63 to 3.19; I = 28%; 3 studies, 140 participants; very low certainty evidence). Results suggest that if the chance of pregnancy following clomiphene is assumed to be 21.5%, the chance following CHM would vary between 14.7% and 46.7%. No study reported data on adverse events. When CHM plus clomiphene was compared to clomiphene (with or without EE/CPA), there was low certainty evidence of a higher pregnancy rate in the CHM plus clomiphene group (OR 3.06, 95% CI 2.05 to 4.55; I = 10%; 6 studies, 470 participants; low certainty evidence). Results suggest that if the chance of pregnancy following clomiphene is assumed to be 31.5%, the chance following CHM plus clomiphene would vary between 48.5% and 67.7%. No data were reported on adverse events. In trials that compared CHM plus follicle aspiration and ovulation induction to follicle aspiration and ovulation induction alone, we are uncertain of the effect of CHM on pregnancy rates (OR 1.62, 95% CI 0.46 to 5.68; 1 study, 44 women; very low certainty evidence). Results suggest that if the chance of pregnancy following follicle aspiration and ovulation induction is assumed to be 29.2%, the chance following CHM with follicle aspiration and ovulation induction would vary between 15.9% and 70%. Reported adverse events included severe luteinised unruptured follicle syndrome (LUFS) (Peto OR 0.60, 95% CI 0.06 to 6.14; 1 study, 44 women; very low certainty evidence), ovarian hyperstimulation syndrome (OHSS) (Peto OR 0.16, 95% CI 0.00 to 8.19; 1 study, 44 women; very low certainty evidence) or multiple pregnancy (Peto OR 0.60, 95% CI 0.06 to 6.14; 1 study, 44 women; very low certainty evidence). These results suggest that if the chances of LUFS, OHSS, and multiple pregnancy following follicle aspiration and ovulation induction are assumed to be 8.3%, 4.2%, and 8.3% respectively, the chances following CHM with follicle aspiration and ovulation induction would be 0.5% to 35.8%, 0% to 26.3% and 0.5% to 35.8% respectively. In trials that compared CHM plus LOD to LOD alone, we are uncertain if CHM improves pregnancy rates (OR 3.50, 95% CI 0.72 to 17.09; 1 study, 30 women; very low certainty evidence). Results suggest that if the chance of pregnancy following LOD is assumed to be 40%, the chance following CHM with LOD would vary between 32.4% and 91.9%. No data were reported on adverse events. We are uncertain of the results in the comparison groups for all outcomes. The certainty of the evidence for all other comparisons and outcomes was very low. The main limitations in the evidence were failure to report live birth or adverse events, failure to describe study methods in adequate detail and imprecision due to very low event rates and wide CIs.
AUTHORS' CONCLUSIONS
There is insufficient evidence to support the use of CHM for subfertile women with PCOS. No data are available on live birth. We are uncertain of the effect of CHM on pregnancy rates for there is no consistent evidence to indicate that CHM influences fertility outcomes. However, we find that the addition of CHM to clomiphene may improve pregnancy rates, but there is very limited, low certainty evidence for this outcome. Furthermore, there is insufficient evidence on adverse effects to indicate whether CHM is safe. In the future, well-designed, carefully conducted RCTs are needed, with a particular focus on the live birth rate and other safety indexes.
Topics: Adult; Bias; Clomiphene; Cyproterone Acetate; Drug Combinations; Drugs, Chinese Herbal; Ethinyl Estradiol; Female; Fertility Agents, Female; Humans; Infertility, Female; Laparoscopy; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Suction; Young Adult
PubMed: 34085287
DOI: 10.1002/14651858.CD007535.pub4