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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 -
European Urology Jan 2022Focal therapy is a promising, minimally invasive strategy to selectively treat localized prostate cancer. A previous systematic review indicated that there is growing... (Review)
Review
CONTEXT
Focal therapy is a promising, minimally invasive strategy to selectively treat localized prostate cancer. A previous systematic review indicated that there is growing evidence for favorable functional outcomes, but that oncological effectiveness was yet to be defined.
OBJECTIVE
To assess the effectiveness of focal therapy in patients with localized prostate cancer in terms of functional and oncological outcomes.
EVIDENCE ACQUISITION
PubMed, Embase, and The Cochrane Library were searched for studies between October 2015 and December 31, 2020. In addition, the research stages were acquired according to the Idea, Development, Exploration, Assessment, Long-term study (IDEAL) recommendations. Ongoing studies were identified through clinical trial registries.
EVIDENCE SYNTHESIS
Seventy-two studies were identified exploring eight different sources of energy to deliver focal therapy in 5827 patients. Twenty-seven studies reported on high-intensity focused ultrasound (HIFU), nine studies on irreversible electroporation, 11 on cryoablation, eight on focal laser ablation and focal brachytherapy, seven on photodynamic therapy (PDT), two on radiofrequency ablation, and one on prostatic artery embolization. The majority of studies were prospective development stage 2a studies (n = 357). PDT and HIFU, both in stage 3, showed promising results. Overall, HIFU studies reported a median of 95% pad-free patients and a median of 85% patients with no clinically significant cancer (CSC) in the treated area. For PDT, no changes in continence were reported and a median of 90% of patients were without CSC. Both treatments were well tolerated.
CONCLUSIONS
Over the past 5 yr, focal therapy has been studied for eight different energy sources, mostly in single-arm stage 2 studies. Although a first randomized controlled trial in focal therapy has been performed, more high-quality evaluations are needed, preferably via multicenter randomized controlled trials with long-term follow-up and predefined assessment of oncological and functional outcomes and health-related quality-of-life measures.
PATIENT SUMMARY
Focal treatment (FT) of prostate cancer has potential, considering that it has less impact on continence and potency than radical treatment. Our systematic review indicates that despite the method being studied extensively over the past half decade, the majority of studies remain in an early research stage. The techniques high-intensity focused ultrasound and photodynamic therapy have shown most progression toward advanced research stages and show favorable results. However, more high-quality evidence is required before FT can become available as a standard treatment.
Topics: Embolization, Therapeutic; Humans; Male; Multicenter Studies as Topic; Prospective Studies; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34489140
DOI: 10.1016/j.eururo.2021.08.005 -
European Urology Jul 2016To date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer. (Comparative Study)
Comparative Study Meta-Analysis Review
CONTEXT
To date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer.
OBJECTIVE
To conduct a meta-analysis assessing the overall and prostate cancer-specific mortality among patients treated with radical prostatectomy or radiotherapy for clinically-localized prostate cancer.
EVIDENCE ACQUISITION
We searched Medline, EMBASE, and the Cochrane Library through June 2015 without year or language restriction, supplemented with hand search, using Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Meta-analysis of Observational Studies in Epidemiology guidelines. We used multivariable adjusted hazard ratios (aHRs) to assess each endpoint. Risk of bias was assessed using the Newcastle-Ottawa scale.
EVIDENCE SYNTHESIS
Nineteen studies of low to moderate risk of bias were selected and up to 118 830 patients were pooled. Inclusion criteria and follow-up length varied between studies. Most studies assessed patients treated with external beam radiotherapy, although some included those treated with brachytherapy separately or with the external beam radiation therapy group. The risk of overall (10 studies, aHR 1.63, 95% confidence interval 1.54-1.73, p<0.00001; I(2)=0%) and prostate cancer-specific (15 studies, aHR 2.08, 95% confidence interval 1.76-2.47, p < 0.00001; I(2)=48%) mortality were higher for patients treated with radiotherapy compared with those treated with surgery. Subgroup analyses by risk group, radiation regimen, time period, and follow-up length did not alter the direction of results.
CONCLUSIONS
Radiotherapy for prostate cancer is associated with an increased risk of overall and prostate cancer-specific mortality compared with surgery based on observational data with low to moderate risk of bias. These data, combined with the forthcoming randomized data, may aid clinical decision making.
PATIENT SUMMARY
We reviewed available studies assessing mortality after prostate cancer treatment with surgery or radiotherapy. While the studies used have a potential for bias due to their observational design, we demonstrated consistently higher mortality for patients treated with radiotherapy rather than surgery.
Topics: Brachytherapy; Humans; Male; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Intensity-Modulated; Survival Rate
PubMed: 26700655
DOI: 10.1016/j.eururo.2015.11.010 -
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 -
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 -
Radiotherapy and Oncology : Journal of... Oct 2017To characterize the cosmetic outcomes and local recurrence (LR) rates of various hypofractionated radiation therapy (RT) regimens for skin basal and squamous cell... (Meta-Analysis)
Meta-Analysis
PURPOSE
To characterize the cosmetic outcomes and local recurrence (LR) rates of various hypofractionated radiation therapy (RT) regimens for skin basal and squamous cell cancers (BCCs/SCCs).
METHODS
A PICOS/PRISMA/MOOSE selection protocol was performed to identify 344 articles published between 1985-2016 evaluating patients with T1-2 N0 SCCs/BCCs treated with definitive RT. Biologically equivalent doses with α/β=3 (BEDs) were calculated. The primary endpoint was post-treatment cosmesis. Mixed effects regression models were used to estimate weighted linear relationships between BED and cosmetic outcomes.
RESULTS
A total of 21 studies were identified detailing the treatment of 9729 skin BCC/SCC patients, across seven countries, with external beam RT (n=9255) or brachytherapy (n=474). Median follow-up was 36months (range: 12-77). Median dose was 45Gy/11 fractions (interquartile range: 37.5Gy/6-55Gy/18) at 4Gy/fraction (interquartile range: 2.5-6Gy); most hypofractionated 18.75Gy/1. There was a trend to decreased "good" cosmesis with higher total dose: -3.4% "good" cosmesis/10Gy BED, p=0.01. Similarly, there was a trend to increased "fair" cosmesis with higher dose: +3.8% "fair" cosmesis/10Gy BEDp=0.006. At a BED of 100Gy, the expected rate of "good" cosmesis is 79% (95% confidence interval: 70%, 88%). Hypofractionated schedules produced similar cosmesis to conventionally fractionated schedules, at the same BED. Fewer than 8% of patients experienced "poor" cosmesis, independent of dose or fractionation regimen.
CONCLUSION
Hypofractionated RT has favorable cosmesis for patients with skin BCCs/SCCs. We recommend clinicians consider these commonly-used regimens, which all have BED of ∼100Gy: 50Gy/15 fractions, 36.75Gy/7 fractions, or 35Gy/5 fractions, as they result in "good" cosmesis in 80% of patients.
Topics: Brachytherapy; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Radiation Dose Hypofractionation; Skin Neoplasms
PubMed: 28843727
DOI: 10.1016/j.radonc.2017.08.011 -
Journal of Contemporary Brachytherapy Feb 2021To evaluate the efficacy and vision-threatening complication rate of plaque brachytherapy with iodine-125 (I), palladium-103 (Pd), and ruthenium-106 (Ru) for treatment... (Review)
Review
PURPOSE
To evaluate the efficacy and vision-threatening complication rate of plaque brachytherapy with iodine-125 (I), palladium-103 (Pd), and ruthenium-106 (Ru) for treatment of iris and iridociliary melanoma.
MATERIAL AND METHODS
A literature review was done based on results yielded from searching PubMed, Embase, and Cochrane database, using following key words: iris melanoma, iridociliary melanoma, brachytherapy, iodine-125 brachytherapy, palladium-103 brachytherapy, and ruthenium-106 brachytherapy. Initially, relationships between mean radiation dose to apex and local recurrence and complication rate were analyzed, and then, a comparison was performed between I, Pd, and Ru studies.
RESULTS
Twelve retrospective and prospective studies were selected, with 491 patients treated primarily with plaque brachytherapy. The range of radiation dose to tumor apex were from 84 to 151.5 Gy. Ranges of mean and median of follow-up time were from 27 to 96 months. Local recurrence rate following brachytherapy ranged from 0 to 8%. A decrease in the average study dose was not associated with an increased local recurrence or metastasis rate ( = 0.373 and 0.195, respectively); however, an increase in radiation dose was associated with higher radiation-related cataract and glaucoma ( < 0.05). The rate of post-treatment glaucoma was higher in studies with I plaque brachytherapy ( = 0.004).
CONCLUSIONS
For brachytherapy of iris and iridociliary melanoma, in a range of 84 to 150 Gy, an increase in radiation dose may increase the risk of complications, while the tumor control rate does not change.
PubMed: 34025736
DOI: 10.5114/jcb.2021.103586 -
European Urology Oct 2021Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are... (Meta-Analysis)
Meta-Analysis
CONTEXT
Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are associated with a high recurrence rate, especially in recurrent USD. Adjunctive measures, such as local drug injection, have been used in an attempt to reduce recurrence rates.
OBJECTIVE
To systematically review evidence for the efficacy and safety of adjuncts used alongside minimally invasive treatment of USD.
EVIDENCE ACQUISITION
A systematic review of the literature published between 1990 and 2020 was conducted in accordance with the PRISMA checklist.
EVIDENCE SYNTHESIS
A total of 26 studies were included in the systematic review, from which 13 different adjuncts were identified, including intralesional injection (triamcinolone, n = 135; prednisolone, n = 58; mitomycin C, n = 142; steroid-mitomycin C-hyaluronidase, n = 103, triamcinolone-mitomycin C-N-acetyl cysteine, n = 50; platelet-rich plasma, n = 44), intraluminal instillation (mitomycin C, n = 20; hyaluronic acid and carboxymethylcellulose, n = 70; captopril, n = 37; 192-iridium brachytherapy, n = 10), application via a lubricated catheter (triamcinolone, n = 124), application via a coated balloon (paclitaxel, n = 106), and enteral application (tamoxifen, n = 30; deflazacort, n = 36). Overall, 13 randomised controlled trials were included in the meta-analysis. Use of any adjunct was associated with a lower rate of USD recurrence (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.27-0.50; p < 0.001) compared to no adjunct use. Of all the adjuncts, mitomycin C was associated with the lowest rate of USD recurrence (intralesional injection: OR 0.23, 95% CI 0.11-0.48; p < 0.001; intraluminal injection: OR 0.11, 95% CI 0.02-0.61; p = 0.01). Urinary tract infection (2.9-14%), bleeding (8.8%), and extravasation (5.8%) were associated with steroid injection; pruritis of the urethra (61%) occurred after instillation of captopril; mild gynaecomastia (6.7%) and gastrointestinal side effects (6.7%) were associated with oral tamoxifen.
CONCLUSIONS
Adjuncts to minimally invasive treatment of USD appear to lower the recurrence rate and are associated with a low adjunct-specific complication rate. However, the studies included were at high risk of bias. Mitomycin C is the adjunct supported by the highest level of evidence.
PATIENT SUMMARY
We reviewed studies on additional therapies (called adjuncts) to minimally invasive treatments for narrowing of the urethra in men. Adjuncts such as mitomycin C injection result in a lower recurrence rate compared to no adjunct use. The use of adjuncts appeared to be safe and complications are uncommon; however, the studies were small and of low quality.
Topics: Captopril; Humans; Injections, Intralesional; Male; Mitomycin; Recurrence; Tamoxifen; Triamcinolone; Urethra; Urethral Stricture
PubMed: 34275660
DOI: 10.1016/j.eururo.2021.06.022 -
Journal of Contemporary Brachytherapy Jun 2021The aim of this study was to evaluate the efficacy and vision-threatening complications of brachytherapy with ruthenium-106 (Ru) plaque to treat uveal melanoma. (Review)
Review
PURPOSE
The aim of this study was to evaluate the efficacy and vision-threatening complications of brachytherapy with ruthenium-106 (Ru) plaque to treat uveal melanoma.
MATERIAL AND METHODS
A literature review was performed based on results from searching PubMed, Embase, Web of Science, Scopus, and Cochrane databases, using the following key words: "choroidal melanoma", "uveal melanoma", "brachytherapy", and "ruthenium-106". We included studies performed on more than 30 patients since 1986, reporting on local control rate, complications rate, mean radiation dose, and mean tumor thickness. The cumulative analysis was performed using Metaprop command of Stata v.16, and meta-regression was conducted based on mean tumor thickness and mean radiation dose to tumor's apex.
RESULTS
Twenty-one retrospective studies were selected, involving 3,913 patients treated primarily with Ru plaque brachytherapy. The range of radiation dose to tumor apex was from 70 Gy to 250 Gy. The local control rate following brachytherapy ranged from 59% to 98%, and the overall weighted mean of local control was 84%. However, the heterogeneity between studies' reports was remarkable ( = 95.40%). Meta-regression based on tumor thickness and mean dose of radiation to the apex showed that the studies' heterogeneity was minimally related to the difference in mean tumor size ( = 92%). The correlation between larger tumor size and lower local control rate was statistically significant (-value = 0.024). There was no significant correlation between the mean radiation dose and local control rate (-value = 0.679). The most commonly reported complications were cataract and radiation-related retinopathy.
CONCLUSIONS
Although the studies' heterogeneity was high, in a prescription dose ranging from 70 Gy to 250 Gy to the tumor apex, Ru brachytherapy seems to be successful in local control of uveal melanoma. The efficacy of Ru in controlling uveal melanomas decreased with the increase in tumor thickness. However, these outcomes should be verified in randomized comparative studies.
PubMed: 34122577
DOI: 10.5114/jcb.2021.106191 -
European Urology Oncology Dec 2023The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain. (Review)
Review
CONTEXT
The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain.
OBJECTIVE
To perform a systematic review to determine the benefits and harms of EBRT-BT.
EVIDENCE ACQUISITION
Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs).
EVIDENCE SYNTHESIS
Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p < 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs.
CONCLUSIONS
EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control.
PATIENT SUMMARY
We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.
PubMed: 38151440
DOI: 10.1016/j.euo.2023.11.018