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Stereotactic body radiation therapy for prostate cancer: systematic review and meta-analysis of prospective trials.

ABSTRACT: Background: Despite the increasing worldwide utilization of stereotactic body radiation therapy (SBRT) for prostate cancer, there are no known summative data regarding its safety and efficacy. To address this knowledge gap, we conducted a PRISMA-guided systematic review and meta-analysis of prospective prostate SBRT trials. Results: Fourteen trials with a total of 2,038 patients were included. Median follow-up was 37 months (range 6-55 months). Most patients had cT1-T2a, Gleason ?7 disease with median pre-treatment PSAs of 5-10; 1,042 (51%) were low-risk, 744 (37%) were intermediate-risk, 158 (8%) were high-risk, and the remainder were unreported. Doses ranged from 33.5-50.0 Gy, most typically in 5 fractions, with nearly all studies delivering nondaily fractionation with some type of daily image guidance. Outcomes were converted into counts at the end of one year. The pooled rate of FFBF was 98% [95% confidence interval, 97-98%]. The pooled rate of late grade ?3 gastrointestinal and genitourinary toxicities were 1% [0-5%] and 2% [1-3%], respectively. Methods: PubMed and Google Scholar were queried for prospective studies evaluating survival and/or toxicity outcomes in SBRT (?5 fractions) for localized prostate cancer. Pooled rates of freedom from biochemical failure (FFBF) and late grades ?3 gastrointestinal (GI) and genitourinary (GU) toxicities were assessed. Meta-analysis of proportions was logit transformed and pooled using generalized linear mixed models (both fixed and random effects) and subsequently back transformed to standard proportions. Conclusions: Despite the lack of long-term follow-up and heterogeneity of the available evidence, prostate SBRT affords appropriate biochemical control with few high-grade toxicities. These data have implications for ongoing worldwide utilization of prostate SBRT as well as ongoing prospective investigations.

SUBMITTER: Cushman TR

PROVIDER: S-EPMC6771455 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Stereotactic body radiation therapy for prostate cancer: systematic review and meta-analysis of prospective trials.

Cushman Taylor R TR Verma Vivek V Khairnar Rahul R Levy Joseph J Simone Charles B CB Mishra Mark V MV

Oncotarget 20190924 54

<b>Background:</b> Despite the increasing worldwide utilization of stereotactic body radiation therapy (SBRT) for prostate cancer, there are no known summative data regarding its safety and efficacy. To address this knowledge gap, we conducted a PRISMA-guided systematic review and meta-analysis of prospective prostate SBRT trials. <b>Results:</b> Fourteen trials with a total of 2,038 patients were included. Median follow-up was 37 months (range 6-55 months). Most patients had cT1-T2a, Gleason ≤7 ...[more]

PMID: 31608141

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Project description: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 I2 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.

Project description:ObjectiveIn contrast to traditional views of incurability, patients with oligometastatic disease present with an opportunity for disease eradication with aggressive treatment. There is mounting evidence in support of the role of stereotactic body radiotherapy (SBRT) in oligometastatic prostate cancer (OMPC).MethodsMEDLINE and EMBASE were queried for prospective cohort studies reporting the outcomes of metachronous OMPC treated with SBRT. The primary outcome was overall local control. Secondary outcomes included androgen deprivation therapy-free survival (ADTFS), biochemical recurrence free survival (BCFS), and progression-free survival (PFS). When appropriate, these endpoints were combined in a meta-analysis.ResultsWe screened 356 abstracts and identified 10 studies to include in our analysis, with a total of 653 patients and 1,111 lesions. The maximum number of lesions included in any single study ranged from 3 to 5. PET-CT staging occurred in 92.4% of all patients. SBRT dose varied, with BED1.5 ranging from 152 to 408. Only one Grade 3 bone toxicity was observed. Meta-analysis reported an overall local control rate of 97% (95% CI, 94-100). Median ADTFS was 24.7 months (95% CI, 20.1-29.2 months). Two-year BCFS, PFS, and ADTFS were 33% (95% CI, 11-55), 39% (95% CI, 24-54), and 52% (95%CI, 41-62), respectively. Patients treated with SBRT were half as likely to experience PSA progression than those on observation when looking at randomized control trial data alone.ConclusionSBRT appears to be effective in controlling overall disease burden in metachronous OMPC patients and is associated with minimal significant toxicity. The current prospective literature is scarce, and further prospective data are needed to guide treatment recommendations.Advances in knowledgeThis study provides a comprehensive summary of the prospective evidence reporting the outcomes of SBRT in the management of OMPC patients. We quantify the rates of local control, biochemical-free recurrence, progression-free survival, and ADT-free survival through meta-analysis.

Project description:ContextThe optimal management of oligometastatic prostate cancer (PCa) is still debated.ObjectiveThe purpose of the present systematic review and meta-analysis is to collect the available evidence to date to better define the role of stereotactic body radiotherapy (SBRT) in selected patients with oligorecurrent PCa.Evidence acquisitionStudy methodology complied with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). All prospective studies including PCa patients with nodal and/or bone oligometastases (one to five lesions) were considered eligible. Heterogeneity between study-specific estimates was tested using chi-square statistics and measured with the I2 index. A pooled estimate was obtained by fitting both fixed-effect and DerSimonian and Laird random-effect model.Evidence synthesisOverall, six works (two randomized and the remainder observational) published between 2013 and 2020 were considered eligible. Globally, data from 445 patients were incorporated, of whom 396 were treated with SBRT (329 in observational studies and the remaining 67 in randomized ones). Regarding local progression-free survival (PFS), five studies reported values close to 100%, while one reported a value of 80% in the observation arm. The benefit in terms of biochemical PFS brought by SBRT was evident in all considered studies. Such a difference in cumulative probabilities between the intervention arm and the comparator arm is maintained even 24 mo after the baseline. All studies but one considered toxicity among the endpoints of interest. Most events were classified as either G1 or G2, and the only G ≥ 3 adverse event was reported in one trial.ConclusionsSBRT is highly cost effective, safe, and with an almost inexistent toxicity risk that makes it the perfect candidate for the optimal management of PCa oligometastatic patients. However, more solid data and a higher level of evidence are needed to affirm its role in the management of these patients.Patient summaryIn this work, we reviewed available evidence on the use of stereotactic body radiotherapy in treating oligometastatic prostate cancer patients. We found good evidence that radiotherapy brings important benefits in overall treatment efficacy without major side effects.

Project description:PurposeTo perform a systematic review and pooled meta-analysis of adrenal metastasis stereotactic body radiation therapy (SBRT) outcomes, treatment characteristics, and toxicity to define the efficacy and propose guidelines for intervention.Methods and materialsWe performed a comprehensive literature search of the Embase and PubMed databases of studies reporting outcome or toxicity data for photon-based SBRT of adrenal metastases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We then conducted a meta-analysis to estimate pooled overall response, local control (LC), and overall survival and analyzed these outcomes in the context of dosimetric parameters and toxicity using metaregression.ResultsThirty-nine studies published between 2009 and 2019 reporting outcomes on 1006 patients were included. The median follow-up was 12 months, and the median biological equivalent dose (BED10, alpha/beta = 10) was 67 Gy. The pooled overall response was 54.6% (95% confidence interval [CI], 46.5%-62.5%). The pooled 1- and 2-year rates of LC were 82% (95% CI, 74%-88%) and 63% (95% CI, 50%-74%), respectively, and the pooled 1- and 2-year overall survival rates were 66% (95% CI, 57%-74%) and 42% (95% CI, 31%-53%), respectively. There was a strong positive association between SBRT dose and 1- and 2-year LC (P < .0001, P = .0002) and an association with 2-year OS (P = .03). Based on a metaregression of dose and LC, BED10 of 60 Gy, 80 Gy, and 100 Gy predicted 1-year LC of 70.5%, 84.8%, and 92.9% and 2-year LC of 47.8%, 70.1%, and 85.6%, respectively. The overall rate of grade 3 or higher toxicity was 1.8%.ConclusionsSBRT of adrenal metastases provides good 1-year LC with an excellent safety profile, and dose escalation may be associated with improved LC. Prospective studies are needed to validate these findings and determine whether there are subsets of patients for whom adrenal metastasis-directed SBRT may confer a survival advantage.

Project description:ObjectiveStereotactic body radiation therapy is the preferred treatment modality for patients with inoperable early-stage non-small cell lung cancer. However, comparative outcomes between stereotactic body radiation therapy and surgery for high-risk patients remain controversial. The primary aim of the present meta-analysis was to assess overall survival in matched and unmatched patient cohorts undergoing stereotactic body radiation therapy or surgery. Secondary end points included cancer-specific survival, disease-free survival, disease recurrence, and perioperative outcomes.MethodsA systematic review of relevant studies was performed through online databases using predefined criteria. The most updated studies were selected for meta-analysis according to unmatched and matched patient cohorts.ResultsThirty-two studies were identified in the systematic review, and 23 were selected for quantitative analysis. Surgery was associated with superior overall survival in both unmatched (odds ratio, 2.49; 95% confidence interval, 2.10-2.94; P < .00001) and matched (odds ratio, 1.71; 95% confidence interval, 1.52-1.93; P < .00001) cohorts. Subgroup analysis demonstrated superior overall survival for lobectomy and sublobar resection compared with stereotactic body radiation therapy. In unmatched and matched cohorts, cancer-specific survival, disease-free survival, and freedom from locoregional recurrence were superior after surgery. However, stereotactic body radiation therapy was associated with fewer perioperative deaths.ConclusionsThe current evidence suggests surgery is superior to stereotactic body radiation therapy in terms of mid- and long-term clinical outcomes; stereotactic body radiation therapy is associated with lower perioperative mortality. However, the improved outcomes after surgery may be due at least in part to an imbalance of baseline characteristics. Future studies should aim to provide histopathologic confirmation of malignancy and compare stereotactic body radiation therapy with minimally invasive anatomical resections.

Project description:PurposeTo our knowledge it is unknown whether stereotactic body radiation therapy of prostate cancer is a substitute for other radiation treatments or surgery, or for expanding the pool of patients who undergo treatment instead of active surveillance.Materials and methodsUsing SEER (Surveillance, Epidemiology, and End Results)-Medicare we identified men diagnosed with prostate cancer between 2007 and 2011. We developed physician-hospital networks by identifying the treating physician of each patient based on the primary treatment received and subsequently assigning each physician to a hospital. We examined the relative distribution of prostate cancer treatments stratified by whether stereotactic body radiation therapy was performed in a network by fitting logistic regression models with robust SEs to account for patient clustering in networks.ResultsWe identified 344 physician-hospital networks, including 30 (8.7%) and 314 (91.3%) in which stereotactic body radiation therapy was and was not performed, respectively. Networks in which that therapy was and was not done did not differ with time in the performance of robotic and radical prostatectomy, and active surveillance (all p >0.05). The relationship with intensity modulated radiation therapy did not show any consistent temporal pattern. In networks in which it was performed less intensity modulated radiation therapy was initially done but there were similar rates in later years. Brachytherapy trends differed among networks in which stereotactic body radiation therapy was vs was not performed with a lower brachytherapy rate in networks in which stereotactic body radiation therapy was done (p=0.03).ConclusionsSurgery and active surveillance rates did not differ in networks in which stereotactic body radiation therapy was vs was not performed but when that therapy was done there was a lower brachytherapy rate. Stereotactic body radiation therapy may represent more of an alternative to brachytherapy than to active surveillance.

Dataset Information

Stereotactic body radiation therapy for prostate cancer: systematic review and meta-analysis of prospective trials.

Publications

Stereotactic body radiation therapy for prostate cancer: systematic review and meta-analysis of prospective trials.

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