-
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 -
JAMA Oncology Jul 2023The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between second-generation AAs and adverse cognitive and functional outcomes, but further data from prospective trials are needed.
OBJECTIVE
To examine whether evidence from randomized clinical trials (RCTs) in prostate cancer supports an association between second-generation AAs and cognitive or functional toxic effects.
DATA SOURCES
PubMed, EMBASE, and Scopus (inception to September 12, 2022).
STUDY SELECTION
Randomized clinical trials of second-generation AAs (abiraterone, apalutamide, darolutamide, or enzalutamide) among individuals with prostate cancer that reported cognitive toxic effects, asthenic toxic effects (eg, fatigue, weakness), or falls were evaluated.
DATA EXTRACTION AND SYNTHESIS
Study screening, data abstraction, and bias assessment were completed independently by 2 reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Enhancing the Quality and Transparency of Health Research reporting guidelines. Tabular counts for all-grade toxic effects were determined to test the hypothesis formulated before data collection.
MAIN OUTCOMES AND MEASURES
Risk ratios (RRs) and SEs were calculated for cognitive toxic effects, asthenic toxic effects, and falls. Because fatigue was the asthenic toxic effect extracted from all studies, data on fatigue are specified in the results. Meta-analysis and meta-regression were used to generate summary statistics.
RESULTS
The systematic review included 12 studies comprising 13 524 participants. Included studies had a low risk of bias. An increased risk of cognitive toxic effects (RR, 2.10; 95% CI, 1.30-3.38; P = .002) and fatigue (RR, 1.34; 95% CI, 1.16-1.54; P < .001) was noted among individuals treated with second-generation AAs vs those in the control arms. The findings were consistent in studies that included traditional hormone therapy in both treatment arms for cognitive toxic effects (RR, 1.77; 95% CI, 1.12-2.79; P = .01) and fatigue (RR, 1.32; 95% CI, 1.10-1.58; P = .003). Meta-regression supported that, across studies, increased age was associated with a greater risk of fatigue with second-generation AAs (coefficient, 0.75; 95% CI, 0.04-0.12; P < .001). In addition, the use of second-generation AAs was associated with an increased risk of falls (RR, 1.87; 95% CI, 1.27-2.75; P = .001).
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis suggest that second-generation AAs carry an increased risk of cognitive and functional toxic effects, including when added to traditional forms of hormone therapy.
Topics: Humans; Male; Androgen Antagonists; Androgen Receptor Antagonists; Androgens; Cognition; Fatigue; Prospective Studies; Prostatic Neoplasms; Quality of Life; Retrospective Studies
PubMed: 37227736
DOI: 10.1001/jamaoncol.2023.0998 -
The Lancet. Oncology Jul 2023Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about... (Meta-Analysis)
Meta-Analysis
Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials.
BACKGROUND
Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about who benefits most. We therefore aimed to obtain up-to-date estimates of the overall effects of docetaxel and to assess whether these effects varied according to prespecified characteristics of the patients or their tumours.
METHODS
The STOPCAP M1 collaboration conducted a systematic review and meta-analysis of individual participant data. We searched MEDLINE (from database inception to March 31, 2022), Embase (from database inception to March 31, 2022), the Cochrane Central Register of Controlled Trials (from database inception to March 31, 2022), proceedings of relevant conferences (from Jan 1, 1990, to Dec 31, 2022), and ClinicalTrials.gov (from database inception to March 28, 2023) to identify eligible randomised trials that assessed docetaxel plus ADT compared with ADT alone in patients with metastatic, hormone-sensitive prostate cancer. Detailed and updated individual participant data were requested directly from study investigators or through relevant repositories. The primary outcome was overall survival. Secondary outcomes were progression-free survival and failure-free survival. Overall pooled effects were estimated using an adjusted, intention-to-treat, two-stage, fixed-effect meta-analysis, with one-stage and random-effects sensitivity analyses. Missing covariate values were imputed. Differences in effect by participant characteristics were estimated using adjusted two-stage, fixed-effect meta-analysis of within-trial interactions on the basis of progression-free survival to maximise power. Identified effect modifiers were also assessed on the basis of overall survival. To explore multiple subgroup interactions and derive subgroup-specific absolute treatment effects we used one-stage flexible parametric modelling and regression standardisation. We assessed the risk of bias using the Cochrane Risk of Bias 2 tool. This study is registered with PROSPERO, CRD42019140591.
FINDINGS
We obtained individual participant data from 2261 patients (98% of those randomised) from three eligible trials (GETUG-AFU15, CHAARTED, and STAMPEDE trials), with a median follow-up of 72 months (IQR 55-85). Individual participant data were not obtained from two additional small trials. Based on all included trials and patients, there were clear benefits of docetaxel on overall survival (hazard ratio [HR] 0·79, 95% CI 0·70 to 0·88; p<0·0001), progression-free survival (0·70, 0·63 to 0·77; p<0·0001), and failure-free survival (0·64, 0·58 to 0·71; p<0·0001), representing 5-year absolute improvements of around 9-11%. The overall risk of bias was assessed to be low, and there was no strong evidence of differences in effect between trials for all three main outcomes. The relative effect of docetaxel on progression-free survival appeared to be greater with increasing clinical T stage (p=0·0019), higher volume of metastases (p=0·020), and, to a lesser extent, synchronous diagnosis of metastatic disease (p=0·077). Taking into account the other interactions, the effect of docetaxel was independently modified by volume and clinical T stage, but not timing. There was no strong evidence that docetaxel improved absolute effects at 5 years for patients with low-volume, metachronous disease (-1%, 95% CI -15 to 12, for progression-free survival; 0%, -10 to 12, for overall survival). The largest absolute improvement at 5 years was observed for those with high-volume, clinical T stage 4 disease (27%, 95% CI 17 to 37, for progression-free survival; 35%, 24 to 47, for overall survival).
INTERPRETATION
The addition of docetaxel to hormone therapy is best suited to patients with poorer prognosis for metastatic, hormone-sensitive prostate cancer based on a high volume of disease and potentially the bulkiness of the primary tumour. There is no evidence of meaningful benefit for patients with metachronous, low-volume disease who should therefore be managed differently. These results will better characterise patients most and, importantly, least likely to gain benefit from docetaxel, potentially changing international practice, guiding clinical decision making, better informing treatment policy, and improving patient outcomes.
FUNDING
UK Medical Research Council and Prostate Cancer UK.
Topics: Male; Humans; Docetaxel; Prostatic Neoplasms; Androgen Antagonists; Disease-Free Survival; Hormones; Antineoplastic Combined Chemotherapy Protocols; Randomized Controlled Trials as Topic
PubMed: 37414011
DOI: 10.1016/S1470-2045(23)00230-9 -
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 -
International Journal of Hyperthermia :... 2021Histotripsy is the first noninvasive, non-ionizing, and non-thermal ablation technology guided by real-time imaging. Using focused ultrasound delivered from outside the...
Histotripsy is the first noninvasive, non-ionizing, and non-thermal ablation technology guided by real-time imaging. Using focused ultrasound delivered from outside the body, histotripsy mechanically destroys tissue through cavitation, rendering the target into acellular debris. The material in the histotripsy ablation zone is absorbed by the body within 1-2 months, leaving a minimal remnant scar. Histotripsy has also been shown to stimulate an immune response and induce abscopal effects in animal models, which may have positive implications for future cancer treatment. Histotripsy has been investigated for a wide range of applications in preclinical studies, including the treatment of cancer, neurological diseases, and cardiovascular diseases. Three human clinical trials have been undertaken using histotripsy for the treatment of benign prostatic hyperplasia, liver cancer, and calcified valve stenosis. This review provides a comprehensive overview of histotripsy covering the origin, mechanism, bioeffects, parameters, instruments, and the latest results on preclinical and human studies.
Topics: Ablation Techniques; Animals; High-Intensity Focused Ultrasound Ablation; Humans; Models, Animal; Neoplasms; Ultrasonography
PubMed: 33827375
DOI: 10.1080/02656736.2021.1905189 -
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 -
Journal of Biomedical Informatics Nov 2023Adequate methods to promptly translate digital health innovations for improved patient care are essential. Advances in Artificial Intelligence (AI) and Machine Learning... (Review)
Review
INTRODUCTION
Adequate methods to promptly translate digital health innovations for improved patient care are essential. Advances in Artificial Intelligence (AI) and Machine Learning (ML) have been sources of digital innovation and hold the promise to revolutionize the way we treat, manage and diagnose patients. Understanding the benefits but also the potential adverse effects of digital health innovations, particularly when these are made available or applied on healthier segments of the population is essential. One of such adverse effects is overdiagnosis.
OBJECTIVE
to comprehensively analyze quantification strategies and data-driven definitions for overdiagnosis reported in the literature.
METHODS
we conducted a scoping systematic review of manuscripts describing quantitative methods to estimate the proportion of overdiagnosed patients.
RESULTS
we identified 46 studies that met our inclusion criteria. They covered a variety of clinical conditions, primarily breast and prostate cancer. Methods to quantify overdiagnosis included both prospective and retrospective methods including randomized clinical trials, and simulations.
CONCLUSION
a variety of methods to quantify overdiagnosis have been published, producing widely diverging results. A standard method to quantify overdiagnosis is needed to allow its mitigation during the rapidly increasing development of new digital diagnostic tools.
Topics: Male; Humans; Retrospective Studies; Artificial Intelligence; Overdiagnosis; Prospective Studies; Prostatic Neoplasms
PubMed: 37769829
DOI: 10.1016/j.jbi.2023.104506 -
The World Journal of Men's Health Jul 2021Prostate cancer is the third most common cancer in men globally, and the most common cancer among men in the United States. Dietary choices may play an important role in... (Review)
Review
Prostate cancer is the third most common cancer in men globally, and the most common cancer among men in the United States. Dietary choices may play an important role in developing prostate cancer; in particular, a higher dairy product intake has been associated with an increased risk of developing prostate cancer. The overall positive association between milk consumption and the risk of prostate cancer development and prostate cancer mortality has been well documented in multiple epidemiological studies. However, there is limited literature on the association between types of milk, as classified by fat content (skim, low fat, and whole), and the risk of developing prostate cancer. When further examining current state of the literature on this topic, there is a number of epidemiologic studies assessing the relationship between prostate cancer and milk consumption. On the contrary, very few experimental studies explore this topic. Further experimental research may be necessary to examine the relationship between dairy and dairy products consumption and the increased risk of development of prostate cancer. At this time, there are no formal clinical recommendations regarding dairy products consumption for patients who are at risk of prostate cancer development or who have a history of prostate cancer. In this manuscript, we sought to systematically review the existing literature on the association between milk consumption classified by fat content, and the risk of developing prostate cancer. These findings may be useful for the clinicians who provide recommendations for the patients at risk of developing prostate cancer.
PubMed: 32777868
DOI: 10.5534/wjmh.200051 -
Cell Proliferation Oct 2023The liver is a common secondary metastasis site of many malignant tumours, such as the colorectum, pancreas, stomach, breast, prostate, and lung cancer. The clinical... (Review)
Review
The liver is a common secondary metastasis site of many malignant tumours, such as the colorectum, pancreas, stomach, breast, prostate, and lung cancer. The clinical management of liver metastases is challenging because of their strong heterogeneity, rapid progression, and poor prognosis. Now, exosomes, small membrane vesicles that are 40-160 nm in size, are released by tumour cells, namely, tumour-derived exosomes (TDEs), and are being increasingly studied because they can retain the original characteristics of tumour cells. Cell-cell communication via TDEs is pivotal for liver pre-metastatic niche (PMN) formation and liver metastasis; thus, TDEs can provide a theoretical basis to intensively study the potential mechanisms of liver metastasis and new insights into the diagnosis and treatment of liver metastasis. Here, we systematically review current research progress about the roles and possible regulatory mechanisms of TDE cargos in liver metastasis, focusing on the functions of TDEs in liver PMN formation. In addition, we discuss the clinical utility of TDEs in liver metastasis, including TDEs as potential biomarkers, and therapeutic approaches for future research reference in this field.
Topics: Humans; Exosomes; Liver Neoplasms; Cell Communication; Pancreas; Biomarkers, Tumor; Tumor Microenvironment; Neoplasm Metastasis
PubMed: 36941028
DOI: 10.1111/cpr.13452 -
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