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Lancet (London, England) Oct 2020It is unclear whether adjuvant or early salvage radiotherapy following radical prostatectomy is more appropriate for men who present with localised or locally advanced... (Comparative Study)
Comparative Study Meta-Analysis
Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data.
BACKGROUND
It is unclear whether adjuvant or early salvage radiotherapy following radical prostatectomy is more appropriate for men who present with localised or locally advanced prostate cancer. We aimed to prospectively plan a systematic review of randomised controlled trials (RCTs) comparing these radiotherapy approaches.
METHODS
We used a prospective framework for adaptive meta-analysis (FAME), starting the review process while eligible trials were ongoing. RCTs were eligible if they aimed to compare immediate adjuvant radiotherapy versus early salvage radiotherapy, following radical prostatectomy in men (age ≥18 years) with intermediate-risk or high-risk, localised or locally advanced prostate cancer. We searched trial registers and conference proceedings until July 8, 2020, to identify eligible RCTs. By establishing the ARTISTIC collaboration with relevant trialists, we were able to anticipate when eligible trial results would emerge, and we developed and registered a protocol with PROSPERO before knowledge of the trial results (CRD42019132669). We used a harmonised definition of event-free survival, as the time from randomisation until the first evidence of either biochemical progression (prostate-specific antigen [PSA] ≥0·4 ng/mL and rising after completion of any postoperative radiotherapy), clinical or radiological progression, initiation of a non-trial treatment, death from prostate cancer, or a PSA level of at least 2·0 ng/mL at any time after randomisation. We predicted when we would have sufficient power to assess whether adjuvant radiotherapy was superior to early salvage radiotherapy. Investigators supplied results for event-free survival, both overall and within predefined patient subgroups. Hazard ratios (HRs) for the effects of radiotherapy timing on event-free survival and subgroup interactions were combined using fixed-effect meta-analysis.
FINDINGS
We identified three eligible trials and were able to obtain updated results for event-free survival for 2153 patients recruited between November, 2007, and December, 2016. Median follow-up ranged from 60 months to 78 months, with a maximum follow-up of 132 months. 1075 patients were randomly assigned to receive adjuvant radiotherapy and 1078 to a policy of early salvage radiotherapy, of whom 421 (39·1%) had commenced treatment at the time of analysis. Patient characteristics were balanced within trials and overall. Median age was similar between trials at 64 or 65 years (with IQRs ranging from 59 to 68 years) across the three trials and most patients (1671 [77·6%]) had a Gleason score of 7. All trials were assessed as having low risk of bias. Based on 270 events, the meta-analysis showed no evidence that event-free survival was improved with adjuvant radiotherapy compared with early salvage radiotherapy (HR 0·95, 95% CI 0·75-1·21; p=0·70), with only a 1 percentage point (95% CI -2 to 3) change in 5-year event-free survival (89% vs 88%). Results were consistent across trials (heterogeneity p=0·18; I=42%).
INTERPRETATION
This collaborative and prospectively designed systematic review and meta-analysis suggests that adjuvant radiotherapy does not improve event-free survival in men with localised or locally advanced prostate cancer. Until data on long-term outcomes are available, early salvage treatment would seem the preferable treatment policy as it offers the opportunity to spare many men radiotherapy and its associated side-effects.
FUNDING
UK Medical Research Council.
Topics: Biomarkers, Tumor; Disease-Free Survival; Humans; Male; Neoplasm Grading; Prospective Studies; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Salvage Therapy
PubMed: 33002431
DOI: 10.1016/S0140-6736(20)31952-8 -
European Urology Mar 2021Molecular biomarkers aim to address the established limitations of clinicopathologic factors to accurately risk stratify patients with prostate cancer (PCa). Questions... (Review)
Review
CONTEXT
Molecular biomarkers aim to address the established limitations of clinicopathologic factors to accurately risk stratify patients with prostate cancer (PCa). Questions remain as to whether sufficient evidence supports adoption of these biomarkers for clinical use.
OBJECTIVE
To perform a systematic review of the available evidence supporting the clinical utility of the Decipher genomic classifier (GC).
EVIDENCE ACQUISITION
The review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by searching PubMed and conference abstracts from January 2010 to June 2020. Evidence was then graded using the criteria of Simon et al (Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 2009;101:1446-52) and American Urology Association (AUA) criteria.
EVIDENCE SYNTHESIS
In total, 42 studies and 30407 patients were included. GC performance data were available for localized, postprostatectomy, nonmetastatic castration-resistant, and metastatic hormone-sensitive PCa as part of retrospective studies (n=12141), prospective registries (n=17053), and prospective and post hoc randomized trial analyses (n=1213). In 32 studies (n=12600), the GC was independently prognostic for all study endpoints (adverse pathology, biochemical failure, metastasis, and cancer-specific and overall survival) on multivariable analysis and improved the discrimination over standard of care in 24 studies (n=8543). GC use changed the management in active surveillance (number needed to test [NNT]=9) and postprostatectomy (NNT=1.5-4) settings in five studies (n=4331). Evidence strength was levels 1 and 2 by the Simon criteria for all disease states other than high-risk PCa, and grades A and B by AUA criteria depending on disease state.
CONCLUSIONS
Consistent data are now present from diverse levels of evidence, which when viewed together, have demonstrated clinical utility of the GC in PCa. The utility of the GC is strongest for intermediate-risk PCa and postprostatectomy decision-making.
PATIENT SUMMARY
In this paper, we review the evidence of the Decipher genomic classification tool for men with prostate cancer. We found consistent evidence that the test helps identify which cancers are more or less aggressive, which in turn aids in personalized treatment decision-making.
Topics: Genome; Genomics; Humans; Male; Prospective Studies; Prostatic Neoplasms; Retrospective Studies; United States
PubMed: 33293078
DOI: 10.1016/j.eururo.2020.11.021 -
International Braz J Urol : Official... 2022Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors,... (Review)
Review
PURPOSE
Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa.
MATERIAL AND METHODS
We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included.
RESULTS
Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade.
CONCLUSIONS
This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.
Topics: Humans; Male; Neoplasm Recurrence, Local; Prostatic Neoplasms; Salvage Therapy; Treatment Outcome; Ultrasound, High-Intensity Focused, Transrectal
PubMed: 34003610
DOI: 10.1590/S1677-5538.IBJU.2021.0091 -
European Urology Oncology Jun 2022In the past 10 yr, several agents based on prostate-specific membrane antigen (PSMA) for positron emission tomography imaging have been introduced in clinical practice... (Review)
Review
[Ga]Ga-PSMA Versus [F]PSMA Positron Emission Tomography/Computed Tomography in the Staging of Primary and Recurrent Prostate Cancer. A Systematic Review of the Literature.
CONTEXT
In the past 10 yr, several agents based on prostate-specific membrane antigen (PSMA) for positron emission tomography imaging have been introduced in clinical practice for the management of patients with prostate cancer (PCa).
OBJECTIVE
To analyse the available data in the literature to clarify the advantages and disadvantages of [Ga]Ga-PSMA and [F]PSMA in different settings of PCa.
EVIDENCE ACQUISITION
A systematic literature search was made by using two main databases. Only studies published in the past 5 yr (2016-2021) in the English language with >20 enrolled patients were selected. Two reviewers independently appraised each article using a standard protocol. All the studies were analysed using a modified version of the Critical Appraisal Skills Programme checklist for diagnostic test studies.
EVIDENCE SYNTHESIS
The systematic evaluation was made in 12 papers. Based on the quality assessment, the analysed studies demonstrated different methodologies. Three papers focused on the head-to-head comparison between F- and [Ga]Ga-PSMA (n = 123 patients). A matched-pair comparison between F- and [Ga]Ga-PSMA was reported in three papers, including 715 patients. The remaining papers used indiscriminately either Ga-PSMA or [F]PSMA (n = 1.157 patients). [F]PSMA-1007 is superior to [Ga]Ga-PSMA-11 for the identification of local recurrence (less activity close to the bladder for [F]PSMA-1007). Nonspecific/equivocal bone lesions are often recognised at [F]PSMA-1007. [F]DCFPyL is more reproducible for the identification of lymph nodes, and it shows fewer equivocal skeletal lesions and higher inter-reader agreement on skeletal lesions.
CONCLUSIONS
Despite a large body of literature on PSMA radiopharmaceutical agents labelled with Ga or F, there are limited head-to-head or matched-pair comparative data. Certain clinical indications could trigger a preference, whilst caution is needed in interpreting potential false-positive findings, especially with [F]PSMA-1007. Given the excellent performance of all accessible radiopharmaceuticals, the availability of specific tracers will likely guide choice.
PATIENT SUMMARY
In this systematic review, we analysed the currently available literature focused on [Ga] and [F]-labelled prostate-specific membrane antigen. Our purpose is to identify which tracers would be correctly employed for the management of patients with prostate cancer.
Topics: Gallium Isotopes; Gallium Radioisotopes; Humans; Male; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radiopharmaceuticals
PubMed: 35367165
DOI: 10.1016/j.euo.2022.03.004 -
European Urology Dec 2017Current evidence-based management for clinically localised prostate cancer includes active surveillance, surgery, external beam radiotherapy (EBRT) and brachytherapy.... (Comparative Study)
Comparative Study Review
CONTEXT
Current evidence-based management for clinically localised prostate cancer includes active surveillance, surgery, external beam radiotherapy (EBRT) and brachytherapy. The impact of these treatment modalities on quality of life (QoL) is uncertain.
OBJECTIVE
To systematically review comparative studies investigating disease-specific QoL outcomes as assessed by validated cancer-specific patient-reported outcome measures with at least 1 yr of follow-up after primary treatment for clinically localised prostate cancer.
EVIDENCE ACQUISITION
MEDLINE, EMBASE, AMED, PsycINFO, and Cochrane Library were searched to identify relevant studies. Studies were critically appraised for the risk of bias. A narrative synthesis was undertaken.
EVIDENCE SYNTHESIS
Of 11486 articles identified, 18 studies were eligible for inclusion, including three randomised controlled trials (RCTs; follow-up range: 60-72 mo) and 15 nonrandomised comparative studies (follow-up range: 12-180 mo) recruiting a total of 13604 patients. Two RCTs recruited small cohorts and only one was judged to have a low risk of bias. The quality of evidence from observational studies was low to moderate. For a follow-up of up to 6 yr, active surveillance was found to have the lowest impact on cancer-specific QoL, surgery had a negative impact on urinary and sexual function when compared with active surveillance and EBRT, and EBRT had a negative impact on bowel function when compared with active surveillance and surgery. Data from one small RCT reported that brachytherapy has a negative impact on urinary function 1 yr post-treatment, but no significant urinary toxicity was reported at 5 yr.
CONCLUSIONS
This is the first systematic review comparing the impact of different primary treatments on cancer-specific QoL for men with clinically localised prostate cancer, using validated cancer-specific patient-reported outcome measures only. There is robust evidence that choice of primary treatment for localised prostate cancer has distinct impacts on patients' QoL. This should be discussed in detail with patients during pretreatment counselling.
PATIENT SUMMARY
Our review of the current evidence suggests that for a period of up to 6 yr after treatment, men with localised prostate cancer who were managed with active surveillance reported high levels of quality of life (QoL). Men treated with surgery reported mainly urinary and sexual problems, while those treated with external beam radiotherapy reported mainly bowel problems. Men eligible for brachytherapy reported urinary problems up to a year after therapy, but then their QoL returned gradually to as it was before treatment.
Topics: Brachytherapy; Humans; Male; Patient Reported Outcome Measures; Prostatectomy; Prostatic Neoplasms; Quality of Life; Radiotherapy; Watchful Waiting
PubMed: 28757301
DOI: 10.1016/j.eururo.2017.06.035 -
European Urology Apr 2020Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment.... (Meta-Analysis)
Meta-Analysis
Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer-Updated Diagnostic Utility, Sensitivity, Specificity, and Distribution of Prostate-specific Membrane Antigen-avid Lesions: A Systematic Review and Meta-analysis.
CONTEXT
Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility of Ga-PSMA PET in this setting.
OBJECTIVE
To perform a systematic review and meta-analysis to update reported predictors of positive Ga-PSMA PET according to prior therapy and proportion of positivity in various anatomical locations with sensitivity and specificity profiles.
EVIDENCE ACQUISITION
We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models.
EVIDENCE SYNTHESIS
A total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positive Ga-PSMA PET scans increased with higher pre-PET prostate-specific antigen (PSA) levels. For PSA categories 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥2ng/ml, the percentages of positive scans were 33%, 45%, 59%, 75%, and 95%, respectively. No significant differences in positivity were noted between Gleason sums ≤7 and ≥8. Significant differences in positivity after biochemical recurrence in the prostate bed were noted between radical prostatectomy (22%) and radiotherapy (52%) patients. On per-node analysis, high sensitivity (75%) and specificity (99%) were observed.
CONCLUSIONS
Ga-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of >0.2ng/ml (33%) and 0.2-0.5ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings.
PATIENT SUMMARY
Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.
Topics: Antigens, Surface; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Glutamate Carboxypeptidase II; Humans; Male; Neoplasm Staging; Oligopeptides; Positron-Emission Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 30773328
DOI: 10.1016/j.eururo.2019.01.049 -
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 Epidemiology Aug 2022Since the 1990s, most nations have had a reduction or stabilisation in prostate cancer mortality. However, socioeconomic differences in disease specific mortality and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since the 1990s, most nations have had a reduction or stabilisation in prostate cancer mortality. However, socioeconomic differences in disease specific mortality and survival have persisted. This has been partially attributed to differences in treatment choices. The aim of this systematic review and meta-analysis was to describe and quantify socioeconomic differences in use of prostate cancer treatment in the literature.
METHODS
MEDLINE, CINAHL and Embase were searched from 01 January 2000-01 April 2021 to identify articles that reported use of prostate cancer treatment by socioeconomic status. Random effects meta-analysis was used to analyse socioeconomic differences in treatment where there was more than one study for treatment type. A modified version of the Newcastle-Ottawa Scale was used to assess risk of bias.
RESULTS
Out of 7267 articles identified, eight met the inclusion criteria and six were analysed using meta-analysis. Meta-analysis could only be completed for non-active treatment (watchful waiting/active surveillance). Lower education was associated with non-active treatment (OR=0.90, [95% CI 0.83-0.98], p=0.02, I=67%), however, level of income was not (OR=0.87, [CI 0.75-1.02], p=0.08, I=94%). Sensitivity analysis of studies where active surveillance was the outcome (n=3), indicated no associations with level of income (OR=0.91, [95% CI 0.82-1.01], p=0.08, I=52%) or education (OR=0.88, [95% CI 0.70-1.10], p=0.25, I=79%). All studies were assessed as high-risk of bias.
DISCUSSION
The relationship between socioeconomic status and prostate cancer treatment depended on the socioeconomic variable being used, the treatment type and how it was defined in research. Considerable methodological limitations were identified. Further research should improve on previous findings and address current gaps.
Topics: Humans; Male; Prostatic Neoplasms; Socioeconomic Factors
PubMed: 35526516
DOI: 10.1016/j.canep.2022.102164 -
Urologic Oncology Jun 2023Meningeal metastases (MM) are a rare progression in advanced prostate. Here we aimed to characterize the incidence, clinical presentation, and outcomes of patients with... (Review)
Review
Meningeal metastases (MM) are a rare progression in advanced prostate. Here we aimed to characterize the incidence, clinical presentation, and outcomes of patients with MM, including dural and leptomeningeal metastases, from primary prostate cancer. A systematic search was performed on MEDLINE, EMBASE, Scopus, and Web of Science. Studies that included patients who developed MM from primary prostate cancer were abstracted. Assessed outcomes included time from primary cancer to MM and MM to death, and clinical presentation of MM, among others. Case reports were compared qualitatively, while observational studies were pooled for quantitative synthesis. The systematic review was prospectively registered on PROSPERO (CRD42020205378). Our institutional series, 11 observational studies, and 46 case reports were synthesized, comprising a total of 191 patients. From the observational studies, the mean age at developing MM was 63.0 years (range: 58.4, 70.9). Presenting neurological symptoms were variable and largely depended on location of MM. The mean time from prostate cancer to MM was 54.6 months (range: 21.0, 101.5), and the mean time from MM to death was 9.0 months (range: 2.6, 23.0). Patients requiring resection for MM had shorter survival after disease progression compared to patients receiving radiation or supportive therapy. All articles had at least moderate risk of bias. We describe the largest synthesis of patients with progression to MM from prostate cancer. Current evidence is very low-quality and primarily stems from small observational studies. Neurological symptoms in the setting of advanced prostate cancer, especially in high-risk disease, warrants radiographic imaging for MM. Further prospective research on risk factors and treatment for MM is warranted.
Topics: Humans; Male; Prostate; Prostatic Neoplasms
PubMed: 36088245
DOI: 10.1016/j.urolonc.2022.08.004 -
Reviews on Environmental Health Sep 2016Investigations about the association between prostate cancer and environmental and/or occupational pesticide exposure have evidenced a possible role of these chemical... (Review)
Review
INTRODUCTION
Investigations about the association between prostate cancer and environmental and/or occupational pesticide exposure have evidenced a possible role of these chemical substances on tumor etiology, related to their action as endocrine disruptors.
OBJECTIVE
To assess the association between pesticide exposure and prostate cancer by conducting a systematic review of the scientific literature.
MATERIALS AND METHODS
Articles published until August 18, 2015 were searched in the databases MEDLINE/Pubmed, Scielo, and Lilacs using the keywords "pesticides" and "prostate cancer". Only the analytical observational studies whose methodological quality met the criteria established by the New Castle-Ottawa scale were included in this review.
RESULTS
The review included 49 studies published between 1993 and 2015. All studies were in English and analyzed exposure to pesticides and/or agricultural activities. Most studies (32 articles) found a positive association between prostate cancer and pesticides or agricultural occupations, with estimates ranging from 1.01 to 14.10.
CONCLUSION
The evidence provided by the reviewed studies indicates a possible association between the development of prostate cancer and pesticide exposure and/or agricultural occupations.
Topics: Agriculture; Environmental Exposure; Humans; Male; Observational Studies as Topic; Occupational Exposure; Pesticides; Prostatic Neoplasms
PubMed: 27244877
DOI: 10.1515/reveh-2016-0001