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European Urology Aug 2023Prostate cancer (PCa) is one of the most common cancers worldwide. Understanding the epidemiology and risk factors of the disease is paramount to improve primary and... (Review)
Review
CONTEXT
Prostate cancer (PCa) is one of the most common cancers worldwide. Understanding the epidemiology and risk factors of the disease is paramount to improve primary and secondary prevention strategies.
OBJECTIVE
To systematically review and summarize the current evidence on the descriptive epidemiology, large screening studies, diagnostic techniques, and risk factors of PCa.
EVIDENCE ACQUISITION
PCa incidence and mortality rates for 2020 were obtained from the GLOBOCAN database of the International Agency for Research on Cancer. A systematic search was performed in July 2022 using PubMed/MEDLINE and EMBASE biomedical databases. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and was registered in PROSPERO (CRD42022359728).
EVIDENCE SYNTHESIS
Globally, PCa is the second most common cancer, with the highest incidence in North and South America, Europe, Australia, and the Caribbean. Risk factors include age, family history, and genetic predisposition. Additional factors may include smoking, diet, physical activity, specific medications, and occupational factors. As PCa screening has become more accepted, newer approaches such as magnetic resonance imaging (MRI) and biomarkers have been implemented to identify patients who are likely to harbor significant tumors. Limitations of this review include the evidence being derived from meta-analyses of mostly retrospective studies.
CONCLUSIONS
PCa remains the second most common cancer among men worldwide. PCa screening is gaining acceptance and will likely reduce PCa mortality at the cost of overdiagnosis and overtreatment. Increasing use of MRI and biomarkers for the detection of PCa may mitigate some of the negative consequences of screening.
PATIENT SUMMARY
Prostate cancer (PCa) remains the second most common cancer among men, and screening for PCa is likely to increase in the future. Improved diagnostic techniques can help reduce the number of men who need to be diagnosed and treated to save one life. Avoidable risk factors for PCa may include factors such as smoking, diet, physical activity, specific medications, and certain occupations.
Topics: Male; Humans; Retrospective Studies; Prostatic Neoplasms; Prostate; Risk Factors; Prostate-Specific Antigen
PubMed: 37202314
DOI: 10.1016/j.eururo.2023.04.021 -
European Urology Feb 2021To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy...
OBJECTIVE
To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa).
EVIDENCE ACQUISITION
The panel performed a literature review of new data, covering the time frame between 2016 and 2020. The guidelines were updated and a strength rating for each recommendation was added based on a systematic review of the evidence.
EVIDENCE SYNTHESIS
A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. Risk-adapted screening should be offered to men at increased risk from the age of 45 yr and to breast cancer susceptibility gene (BRCA) mutation carriers, who have been confirmed to be at risk of early and aggressive disease (mainly BRAC2), from around 40 yr of age. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is performed, a combination of targeted and systematic biopsies must be offered. There is currently no place for the routine use of tissue-based biomarkers. Whilst prostate-specific membrane antigen positron emission tomography computed tomography is the most sensitive staging procedure, the lack of outcome benefit remains a major limitation. Active surveillance (AS) should always be discussed with low-risk patients, as well as with selected intermediate-risk patients with favourable International Society of Urological Pathology (ISUP) 2 lesions. Local therapies are addressed, as well as the AS journey and the management of persistent prostate-specific antigen after surgery. A strong recommendation to consider moderate hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term hormonal treatment.
CONCLUSIONS
The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management.
PATIENT SUMMARY
Updated prostate cancer guidelines are presented, addressing screening, diagnosis, and local treatment with curative intent. These guidelines rely on the available scientific evidence, and new insights will need to be considered and included on a regular basis. In some cases, the supporting evidence for new treatment options is not yet strong enough to provide a recommendation, which is why continuous updating is important. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them.
Topics: Early Detection of Cancer; Humans; Male; Prostatic Neoplasms
PubMed: 33172724
DOI: 10.1016/j.eururo.2020.09.042 -
European Urology Sep 2021Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality.
OBJECTIVE
To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy.
EVIDENCE ACQUISITION
We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities.
EVIDENCE SYNTHESIS
A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified.
CONCLUSIONS
Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted.
PATIENT SUMMARY
In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.
Topics: Brachytherapy; Cryotherapy; High-Intensity Focused Ultrasound Ablation; Humans; Male; Neoplasm Recurrence, Local; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Radiation Dosage; Radiosurgery; Salvage Therapy
PubMed: 33309278
DOI: 10.1016/j.eururo.2020.11.010 -
Radiation Oncology (London, England) Mar 2021Due to improved imaging sensitivity, the term "oligometastatic" prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed...
BACKGROUND
Due to improved imaging sensitivity, the term "oligometastatic" prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed therapy (MDT). There are two types of radiation based MDT applied when treating oligometastatic disease: (1) stereotactic body radiation therapy (SBRT) generally used for bone metastases; or (2) SBRT for isolated nodal oligometastases combined with prophylactic elective nodal radiotherapy. This review aims to summarize current evidence data, which may shed light on the optimal management of this heterogeneous group of patients.
METHODS
A systematic review of the Medline database through PubMed was performed according to PRISMA guidelines. All relevant studies published up to November 2020 were identified and screened. Fifty-six titles were included. Besides outcome parameters, different prognostic and predictive factors were assessed, including site of metastases, time between primary treatment and MDT, use of systemic therapies, hormone sensitivity, as well as pattern of recurrence.
FINDINGS
Evidence consists largely of retrospective case series and no consistent precise definition of oligometastasis exists, however, most investigators seem to acknowledge the need to distinguish between patients presenting with what is frequently called "synchronous" versus "metachronous" oligometastatic disease. Available data on radiotherapy as MDT demonstrate high local control rates and a small but relevant proportion of patients without progressive disease after 2 years. This holds true for both hormone sensitive and castration resistant prostate cancer diseases. The use of Ga-PSMA PET/CT for staging increased dramatically. Radiation doses and field sizes varied considerably among the studies. The search for relevant prognostic and predictive factors is ongoing.
CONCLUSIONS
To our best knowledge this review on oligometastatic prostate cancer included the largest number of original articles. It demonstrates the therapeutic potential and challenges of MDT for oligometastatic prostate cancer. Prospective studies are under way and will provide further high-level evidence.
Topics: Bone Neoplasms; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Prostatic Neoplasms; Radiosurgery; Radiotherapy Dosage
PubMed: 33750437
DOI: 10.1186/s13014-021-01776-8 -
European Urology Jul 2023Whether prostate-specific membrane antigen positron emission tomography (PSMA-PET) should replace conventional imaging modalities (CIM) for initial staging of... (Meta-Analysis)
Meta-Analysis Review
Head-to-head Comparison of the Diagnostic Accuracy of Prostate-specific Membrane Antigen Positron Emission Tomography and Conventional Imaging Modalities for Initial Staging of Intermediate- to High-risk Prostate Cancer: A Systematic Review and Meta-analysis.
CONTEXT
Whether prostate-specific membrane antigen positron emission tomography (PSMA-PET) should replace conventional imaging modalities (CIM) for initial staging of intermediate-high risk prostate cancer (PCa) requires definitive evidence on their relative diagnostic abilities.
OBJECTIVE
To perform head-to-head comparisons of PSMA-PET and CIM including multiparametric magnetic resonance imaging (mpMRI), computed tomography (CT) and bone scan (BS) for upfront staging of tumour, nodal, and bone metastasis.
EVIDENCE ACQUISITION
A search of the PubMed, EMBASE, CENTRAL, and Scopus databases was conducted from inception to December 2021. Only studies in which patients underwent both PSMA-PET and CIM and imaging was referenced against histopathology or composite reference standards were included. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist and its extension for comparative reviews (QUADAS-C). Pairwise comparisons of the sensitivity and specificity of PSMA-PET versus CIM were performed by adding imaging modality as a covariate to bivariate mixed-effects meta-regression models. The likelihood ratio test was applied to determine whether statistically significant differences existed.
EVIDENCE SYNTHESIS
A total of 31 studies (2431 patients) were included. PSMA-PET/MRI was more sensitive than mpMRI for detection of extra-prostatic extension (78.7% versus 52.9%) and seminal vesicle invasion (66.7% versus 51.0%). For nodal staging, PSMA-PET was more sensitive and specific than mpMRI (73.7% versus 38.9%, 97.5% versus 82.6%) and CT (73.2% versus 38.5%, 97.8% versus 83.6%). For bone metastasis staging, PSMA-PET was more sensitive and specific than BS with or without single-photon emission computerised tomography (98.0% versus 73.0%, 96.2% versus 79.1%). A time interval between imaging modalities >1 month was identified as a source of heterogeneity across all nodal staging analyses.
CONCLUSIONS
Direct comparisons revealed that PSMA-PET significantly outperforms CIM, which suggests that PSMA-PET should be used as a first-line approach for the initial staging of PCa.
PATIENT SUMMARY
We reviewed direct comparisons of the ability of a scan method called PSMA-PET (prostate-specific membrane antigen positron emission tomography) and current imaging methods to detect the spread of prostate cancer outside the prostate gland. We found that PSMA-PET is more accurate for detection of the spread of prostate cancer to adjacent tissue, nearby lymph nodes, and bones.
Topics: Male; Humans; Prostate; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostatic Neoplasms; Magnetic Resonance Imaging; Gallium Radioisotopes; Neoplasm Staging
PubMed: 37032189
DOI: 10.1016/j.eururo.2023.03.001 -
European Urology Oncology Dec 2022Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm balance remain unclear.
OBJECTIVE
To assess clinical effectiveness regarding survival and HRQoL, safety, and benefit-harm balance of mHSPC treatments.
EVIDENCE ACQUISITION
We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov until March 1, 2022. Randomized controlled trials (RCTs) comparing docetaxel, abiraterone, enzalutamide, apalutamide, darolutamide, and radiotherapy combined with androgen deprivation therapy (ADT) mutually or with ADT alone were eligible. Three reviewers independently performed screening, data extraction, and risk of bias assessment in duplicate.
EVIDENCE SYNTHESIS
Across ten RCTs, we found relevant survival benefits for ADT + docetaxel (high certainty according to the Grading of Recommendations, Assessment, Development and Evaluation [GRADE]), ADT + abiraterone (moderate certainty), ADT + enzalutamide (low certainty), ADT + apalutamide (high certainty), and ADT + docetaxel + darolutamide (high certainty) compared with ADT alone. ADT + radiotherapy appeared effective only in low-volume de novo mHSPC. We found a short-term HRQoL decrease lasting 3-6 mo for ADT + docetaxel (moderate certainty) and a potential HRQoL benefit for ADT + abiraterone up to 24 mo of follow-up (moderate certainty) compared with ADT alone. There was no difference in HRQoL for ADT + enzalutamide, ADT + apalutamide, or ADT + radiotherapy over ADT alone (low-high certainty). Grade 3-5 adverse effect rates were increased with all systemic combination treatments. A benefit-harm assessment showed high probabilities (>60%) for a net clinical benefit with ADT + abiraterone, ADT + enzalutamide, and ADT + apalutamide, while ADT + docetaxel and ADT + docetaxel + darolutamide appeared unlikely (<40%) to be beneficial.
CONCLUSIONS
Despite substantial survival benefits, no systemic combination treatment showed a clear HRQoL improvement compared with ADT alone. We found evidence for a short-term HRQoL decline with ADT + docetaxel and a higher net clinical benefit with ADT + abiraterone, ADT + apalutamide and ADT + enzalutamide. While individualized decision-making remains important and economic factors need to be considered, the evidence may support a general preference for the combination of ADT with androgen receptor axis-targeted therapies over docetaxel-containing strategies.
PATIENT SUMMARY
We assessed different combination treatments for metastatic hormone-sensitive prostate cancer. While survival was better with all systemic combination treatments, there was no clear improvement in health-related quality of life compared with androgen deprivation therapy alone. Novel hormonal combination treatments had a more favorable benefit-harm balance than combination treatments that include chemotherapy.
Topics: Male; Humans; Docetaxel; Network Meta-Analysis; Androgens; Prostatic Neoplasms
PubMed: 35599144
DOI: 10.1016/j.euo.2022.04.007 -
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 Feb 2021To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy &...
OBJECTIVE
To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC).
EVIDENCE ACQUISITION
The working panel performed a literature review of the new data (2016-2019). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature.
EVIDENCE SYNTHESIS
Prostate-specific membrane antigen positron emission tomography computed tomography scanning has developed an increasingly important role in men with biochemical recurrence after local therapy. Early salvage radiotherapy after radical prostatectomy appears as effective as adjuvant radiotherapy and, in a subset of patients, should be combined with androgen deprivation. New treatments have become available for men with metastatic hormone-sensitive prostate cancer (PCa), nonmetastatic CRPC, and metastatic CRPC, along with a role for local radiotherapy in men with low-volume metastatic hormone-sensitive PCa. Also included is information on quality of life outcomes in men with PCa.
CONCLUSIONS
The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/).
PATIENT SUMMARY
This article summarises the guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are evidence based and guide the clinician in the discussion with the patient on the treatment decisions to be taken. These guidelines are updated every year; this summary spans the 2017-2020 period of new evidence.
Topics: Humans; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prostatic Neoplasms
PubMed: 33039206
DOI: 10.1016/j.eururo.2020.09.046 -
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 -
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