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Prostate Cancer and Prostatic Diseases Feb 2022The most recent overall survival (OS) and adverse event (AE) data have not been compared for the three guideline-recommended high-risk non-metastatic... (Meta-Analysis)
Meta-Analysis Review
Overall survival and adverse events after treatment with darolutamide vs. apalutamide vs. enzalutamide for high-risk non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.
BACKGROUND
The most recent overall survival (OS) and adverse event (AE) data have not been compared for the three guideline-recommended high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) treatment alternatives.
METHODS
We performed a systematic review and network meta-analysis focusing on OS and AE according to the most recent apalutamide, enzalutamide, and darolutamide reports. We systematically examined and compared apalutamide vs. enzalutamide vs. darolutamide efficacy and toxicity, relative to ADT according to PRISMA. We relied on PubMed search for most recent reports addressing prospective randomized trials with proven predefined OS benefit, relative to ADT: SPARTAN, PROSPER, and ARAMIS. OS represented the primary outcome and AEs represented secondary outcomes.
RESULTS
Overall, data originated from 4117 observations made within the three trials that were analyzed. Regarding OS benefit relative to ADT, darolutamide ranked first, followed by enzalutamide and apalutamide, in that order. In the subgroup of PSA-doubling time (PSA-DT) ≤ 6 months patients, enzalutamide ranked first, followed by darolutamide and apalutamide in that order. Conversely, in the subgroup of PSA-DT 6-10 months patients, darolutamide ranked first, followed by apalutamide and enzalutamide, in that order. Regarding grade 3+ AEs, darolutamide was most favorable, followed by enzalutamide and apalutamide, in that order.
CONCLUSION
The current network meta-analysis suggests the highest OS efficacy and lowest grade 3+ toxicity for darolutamide. However, in the PSA-DT ≤ 6 months subgroup, the highest efficacy was recorded for enzalutamide. It is noteworthy that study design, study population, and follow-up duration represent some of the potentially critical differences that distinguish between the three studies and remained statistically unaccounted for using the network meta-analysis methodology. Those differences should be strongly considered in the interpretation of the current and any network meta-analyses.
Topics: Benzamides; Humans; Male; Network Meta-Analysis; Nitriles; Phenylthiohydantoin; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Pyrazoles; Thiohydantoins; Treatment Outcome
PubMed: 34054128
DOI: 10.1038/s41391-021-00395-4 -
JAMA Oncology Mar 2021Multiple systemic treatments are available for metastatic castration-sensitive prostate cancer (mCSPC), with unclear comparative effectiveness and safety and widely... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Multiple systemic treatments are available for metastatic castration-sensitive prostate cancer (mCSPC), with unclear comparative effectiveness and safety and widely varied costs.
OBJECTIVE
To compare the effectiveness and safety determined in randomized clinical trials of systemic treatments for mCSPC.
DATA SOURCES
Bibliographic databases (MEDLINE, Embase, and Cochrane Central), regulatory documents (US Food and Drug Administration and European Medicines Agency), and trial registries (ClinicalTrials.gov and European Union clinical trials register) were searched from inception through November 5, 2019.
STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS
Eligible studies were randomized clinical trials evaluating the addition of docetaxel, abiraterone acetate, apalutamide, or enzalutamide to androgen-deprivation therapy (ADT) for treatment of mCSPC. Two investigators independently performed screening. Discrepancies were resolved through consensus. A Cochrane risk-of-bias tool was used to assess trial quality. Relative effects of competing treatments were assessed by bayesian network meta-analysis and survival models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used.
MAIN OUTCOMES AND MEASURES
Overall survival, radiographic progression-free survival, and serious adverse events (SAEs).
RESULTS
Seven trials with 7287 patients comparing 6 treatments (abiraterone acetate, apalutamide, docetaxel, enzalutamide, standard nonsteroidal antiandrogen, and placebo/no treatment) were identified. Ordered from the most to the least effective determined by results of clinical trials, treatments associated with improved overall survival when added to ADT included abiraterone acetate (hazard ratio [HR], 0.61; 95% credible interval [CI], 0.54-0.70), apalutamide (HR, 0.67; 95% CI, 0.51-0.89), and docetaxel (HR, 0.79; 95% CI, 0.71-0.89); treatments associated with improved radiographic progression-free survival when added to ADT included enzalutamide (HR, 0.39; 95% CI, 0.30-0.50), apalutamide (HR, 0.48; 95% CI, 0.39-0.60), abiraterone acetate (HR, 0.51; 95% CI, 0.45-0.58), and docetaxel (HR, 0.67; 95% CI 0.60-0.74). Docetaxel was associated with substantially increased SAEs (odds ratio, 23.72; 95% CI, 13.37-45.15), abiraterone acetate with slightly increased SAEs (odds ratio, 1.42; 95% CI, 1.10-1.83), and other treatments with no significant increase in SAEs. Risk of bias was noted for 4 trials with open-label design, 3 trials with missing data, and 2 trials with potential unprespecified analyses.
CONCLUSIONS AND RELEVANCE
In this network meta-analysis, as add-on treatments to ADT, abiraterone acetate and apalutamide may provide the largest overall survival benefits with relatively low SAE risks. Although enzalutamide may improve radiographic progression-free survival to the greatest extent, longer follow-up is needed to examine the overall survival benefits associated with enzalutamide.
Topics: Androgen Antagonists; Bayes Theorem; Castration; Humans; Male; Network Meta-Analysis; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome
PubMed: 33443584
DOI: 10.1001/jamaoncol.2020.6973 -
International Journal of Radiation... Jul 2019Utilization of stereotactic body radiation therapy (SBRT) for treatment of localized prostate cancer is increasing. Guidelines and payers variably support the use of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Utilization of stereotactic body radiation therapy (SBRT) for treatment of localized prostate cancer is increasing. Guidelines and payers variably support the use of prostate SBRT. We therefore sought to systematically analyze biochemical recurrence-free survival (bRFS), physician-reported toxicity, and patient-reported outcomes after prostate SBRT.
METHODS AND MATERIALS
A systematic search leveraging Medline via PubMed and EMBASE for original articles published between January 1990 and January 2018 was performed. This was supplemented by abstracts with sufficient extractable data from January 2013 to March 2018. All prospective series assessing curative-intent prostate SBRT for localized prostate cancer reporting bRFS, physician-reported toxicity, and patient-reported quality of life with a minimum of 1-year follow-up were included. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Meta-analyses were performed with random-effect modeling. Extent of heterogeneity between studies was determined by the I and Cochran's Q tests. Meta-regression was performed using Hartung-Knapp methods.
RESULTS
Thirty-eight unique prospective series were identified comprising 6116 patients. Median follow-up was 39 months across all patients (range, 12-115 months). Ninety-two percent, 78%, and 38% of studies included low, intermediate, and high-risk patients. Overall, 5- and 7-year bRFS rates were 95.3% (95% confidence interval [CI], 91.3%-97.5%) and 93.7% (95% CI, 91.4%-95.5%), respectively. Estimated late grade ≥3 genitourinary and gastrointestinal toxicity rates were 2.0% (95% CI, 1.4%-2.8%) and 1.1% (95% CI, 0.6%-2.0%), respectively. By 2 years post-SBRT, Expanded Prostate Cancer Index Composite urinary and bowel domain scores returned to baseline. Increasing dose of SBRT was associated with improved biochemical control (P = .018) but worse late grade ≥3 GU toxicity (P = .014).
CONCLUSIONS
Prostate SBRT has substantial prospective evidence supporting its use, with favorable tumor control, patient-reported quality of life, and levels of toxicity demonstrated. SBRT has sufficient evidence to be supported as a standard treatment option for localized prostate cancer while ongoing trials assess its potential superiority.
Topics: Clinical Trials as Topic; Confidence Intervals; Dose Fractionation, Radiation; Humans; Male; Prospective Studies; Prostatic Neoplasms; Publication Bias; Quality of Life; Radiosurgery; Treatment Outcome
PubMed: 30959121
DOI: 10.1016/j.ijrobp.2019.03.051 -
Medicine May 2019To perform a systematic review and meta-analysis evaluating the perioperative, functional, and oncological outcomes and cost of robot-assisted radical prostatectomy... (Comparative Study)
Comparative Study Meta-Analysis
Robot-assisted and laparoscopic vs open radical prostatectomy in clinically localized prostate cancer: perioperative, functional, and oncological outcomes: A Systematic review and meta-analysis.
BACKGROUND
To perform a systematic review and meta-analysis evaluating the perioperative, functional, and oncological outcomes and cost of robot-assisted radical prostatectomy (RARP), or laparoscopic radical prostatectomy (LRP) comparing with open radical prostatectomy (ORP) in men with clinically localized prostate cancer through all prospective comparative studies.
METHODS
A comprehensive literature search was performed in August 2018 using the Pubmed, Medline, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) and prospective studies including patients with clinically localized prostate cancer were eligible for study inclusion. Cumulative analysis was conducted using Review Manager v. 5.3 software.
RESULTS
Two RCTs and 9 prospective studies were included in this systematic review. There were no significant differences between RARP/LRP and ORP in overall complication rate, major complication rate, overall positive surgical margin (PSM) rate, ≤pT2 tumor PSM rate, ≥pT3 tumor PSM rate. Moreover, RARP/LRP and ORP showed similarity in biochemical recurrence (BCR) rate at 3, 12, 24 months postoperatively. Urinary continence and erectile function at 12 months postoperatively between RARP and ORP are also comparable. RARP/LRP were associated with significantly lower estimated blood loss [mean difference (MD) -749.67, 95% CI -1038.52 to -460.82, P = .001], lower transfusion rate (OR 0.17, 95% CI 0.10 to 0.30, P < .001) and less hospitalization duration (MD -1.18, 95% CI -2.18 to -0.19, P = .02). And RARP/LRP required more operative time (MD 50.02, 95% CI 6.50 to 93.55, P = .02) and cost.
CONCLUSION
RARP/LRP is associated with lower blood loss, transfusion rate and less hospitalization duration. The available data were insufficient to prove the superiority of any surgical approach in terms of postoperative complications, functional and oncologic outcomes.
Topics: Adult; Aged; Humans; Laparoscopy; Male; Margins of Excision; Middle Aged; Operative Time; Postoperative Complications; Prostatectomy; Prostatic Neoplasms; Robotic Surgical Procedures; Treatment Outcome
PubMed: 31145297
DOI: 10.1097/MD.0000000000015770 -
Urologic Oncology Aug 2020Often contraindicated because of the theoretical risk of progression based on the dogma of hormone dependent prostate cancer (CaP), testosterone replacement therapy...
Often contraindicated because of the theoretical risk of progression based on the dogma of hormone dependent prostate cancer (CaP), testosterone replacement therapy (TRT) is increasingly discussed and proposed for hypogonadal patients with localized CaP. To perform a systematic literature review to determine the relationship between TRT and the risk of CaP with a focus on the impact of TRT in the setting of previous or active localized CaP. As of October 15, 2019, systematic review was performed via Medline Embase and Cochrane databases in accordance with the PRISMA guidelines. All full text articles in English published from January 1994 to February 2018 were included. Articles were considered if they reported about the relationship between total testosterone or bioavailable testosterone and CaP. Emphasis was given to prospective studies, series with observational data and randomized controlled trials. Articles about the safety of the testosterone therapy were categorized by type of CaP management (active surveillance or curative treatment by radical prostatectomy, external radiotherapy or brachytherapy). Until more definitive data becomes available, clinicians wishing to treat their hypogonadal patients with localized CaP with TRT should inform them of the lack of evidence regarding the safety of long-term treatment for the risk of CaP progression. However, in patients without known CaP, the evidence seems sufficient to think that androgen therapy does not increase the risk of subsequent discovery of CaP.
Topics: Hormone Replacement Therapy; Humans; Male; Prostatic Neoplasms; Testosterone
PubMed: 32409202
DOI: 10.1016/j.urolonc.2020.04.008 -
Scientific Reports Oct 2023The involvement of human papillomavirus (HPV) in the prostate carcinogenesis is a controversial issue. The presented meta-analysis was carried out to systematize the... (Meta-Analysis)
Meta-Analysis
The involvement of human papillomavirus (HPV) in the prostate carcinogenesis is a controversial issue. The presented meta-analysis was carried out to systematize the currently available research results regarding this question. The meta-analysis includes case-control studies from 1991 to 2022, which were collected from publicly available bibliometric databases. The meta-analysis was performed using Meta-Essentials_1.5 software. We used Begg's and Egger's methods to assess publication bias. Cochran's Q test was used to assess heterogeneity and the I index was employed for calculating the variation in the pooled estimations. The analysis was based on data from 27 case-control studies, which in total yielded 1607 tumour tissue samples of prostate and 1515 control samples (317 samples of normal tissue, 1198 samples of benign prostatic hyperplasia (BPH)). According to the data obtained, there was high risk of prostate cancer by HPV infection in both cases. HPV was found in prostate cancer in 25.8% of cases, while in normal tissue samples the virus was detected in 9.2% of cases and in 17.4% with BPH as a control. In particular, more studies on the association of HPV and prostate cancer are needed to prove the role of HPV in the development of prostate cancer. In addition to the controversial question of whether HPV infection is associated with prostate cancer risk, it is worth considering whether the samples used as a control have an impact on the results. The impact of HPV in prostate tumour tissue samples on outcome should also be investigated.
Topics: Male; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Prostatic Hyperplasia; Papillomaviridae; Prostatic Neoplasms
PubMed: 37789036
DOI: 10.1038/s41598-023-43767-7 -
International Journal of Molecular... Aug 2020Prostate cancer is a major cause of death among men worldwide. Recent preclinical evidence implicates cannabinoids as powerful regulators of cell growth and... (Review)
Review
Prostate cancer is a major cause of death among men worldwide. Recent preclinical evidence implicates cannabinoids as powerful regulators of cell growth and differentiation, as well as potential anti-cancer agents. The aim of this review was to evaluate the effect of cannabinoids on in vivo prostate cancer models. The databases searched included PubMed, Embase, Scopus, and Web of Science from inception to August 2020. Articles reporting on the effect of cannabinoids on prostate cancer were deemed eligible. We identified six studies that were all found to be based on in vivo/xenograft animal models. Results: In PC3 and DU145 xenografts, WIN55,212-2 reduced cell proliferation in a dose-dependent manner. Furthermore, in LNCaP xenografts, WIN55,212-2 reduced cell proliferation by 66-69%. PM49, which is a synthetic cannabinoid quinone, was also found to result in a significant inhibition of tumor growth of up to 90% in xenograft models of LNCaP and 40% in xenograft models of PC3 cells, respectively. All studies have reported that the treatment of prostate cancers in in vivo/xenograft models with various cannabinoids decreased the size of the tumor, the outcomes of which depended on the dose and length of treatment. Within the limitation of these identified studies, cannabinoids were shown to reduce the size of prostate cancer tumors in animal models. However, further well-designed and controlled animal studies are warranted to confirm these findings.
Topics: Animals; Benzoxazines; Cannabinoids; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Humans; Male; Morpholines; Naphthalenes; PC-3 Cells; Prostatic Neoplasms; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 32872551
DOI: 10.3390/ijms21176265 -
Cancer Control : Journal of the Moffitt... Jul 2015The use of radical prostatectomy for the treatment of prostate cancer has been increasing during the last decade partially due to the widespread adoption of the... (Review)
Review
BACKGROUND
The use of radical prostatectomy for the treatment of prostate cancer has been increasing during the last decade partially due to the widespread adoption of the robotic-assisted laparoscopic technique. Although no prospective, randomized controlled trials have compared open radical prostatectomy (ORP) with robotic-assisted laparoscopic radical prostatectomy (RALRP), numerous comparative studies have been retrospectively conducted.
METHODS
A systematic review of the literature was performed to clarify the role and advancement of RALRP. Studies comparing ORP with RALRP that measured outcomes of cancer control, urinary and sexual function, and complications were included. A nonsystematic review was utilized to describe the advancements in the techniques used for RALRP.
RESULTS
RALRP is the procedure of choice when treating localized prostate cancer. This preference is due to the observed improvement in morbidity rates, as evidenced by decreased rates of blood loss and postoperative pain and similar oncological outcomes when compared with ORP. Robotic assistance during surgery is continually being modified and the techniques advanced, as evidenced by improved nerve sparing for preserving potency and reconstruction of the bladder neck to help in the early recovery of urinary continence.
CONCLUSIONS
Morbidity rates should continue to improve with the advancement of minimally invasive techniques for radical prostatectomy. The adoption of robotic assistance during surgery will continue as the applications of robotic-assisted surgery expand into other solid organ malignancies.
Topics: Humans; Laparoscopy; Male; Prostatectomy; Prostatic Neoplasms; Robotic Surgical Procedures
PubMed: 26351883
DOI: 10.1177/107327481502200305 -
Nutrients Feb 2023We conducted a systematic review and meta-analysis to investigate the role of alcohol consumption with the prognosis of prostate cancer (PCa). Published reports were... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analysis to investigate the role of alcohol consumption with the prognosis of prostate cancer (PCa). Published reports were gathered on 15 October 2022, from PUBMED/MEDLINE and EMBASE. We found 19 independent eligible studies on the association between consumption of alcoholic beverages and the risk of fatal PCa (n = 5), PCa mortality (n = 5) in healthy subjects, and PCa patients' survival (n = 7) or surrogates thereof (n = 2). We used random effects meta-analysis to obtain a summary risk estimate (SRE) and 95% confidence intervals (95%CI) for incidence of fatal PCa and PCa mortality. The meta-analysis revealed no association between alcohol consumption and fatal prostate cancer incidence risk in healthy subjects with an indication for publication bias, but omitting the study that mainly increased the between-study heterogeneity, the SRE becomes significant (SRE 1.33, 95%CI 1.12-1.58), and the heterogeneity disappeared ( = 0%) with no indication of publication bias. No association of alcohol consumption was found with mortality risk in PCa patients (SRE 0.97, 95%CI 0.92-1.03) and PCa mortality risk in healthy subjects (SRE 1.03, 95%CI 0.82-1.30). In conclusion, this study suggests that there is some evidence of an association between high alcohol consumption and an increased risk of incidence of fatal prostate cancer in healthy subjects. Given the inconsistencies this result warrants further confirmation.
Topics: Male; Humans; Alcohol Drinking; Prostatic Neoplasms; Prostate; Prognosis; Incidence
PubMed: 36839283
DOI: 10.3390/nu15040925 -
International Journal of Urology :... Mar 2016It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen... (Review)
Review
It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low-risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low-risk prostate cancer without compromising cancer-specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side-effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized.
Topics: Androgen Antagonists; Androgens; Disease Progression; Humans; Male; Medical Overuse; Neoplasm Grading; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Watchful Waiting
PubMed: 26621054
DOI: 10.1111/iju.13016