Abstract
BACKGROUND: Early and mid-term safety and efficacy of aneurysm treatment with the Pipeline Embolization Device (PED) has been well demonstrated in prior studies.
OBJECTIVE: To present 5-yr ...follow-up for patients treated in the Pipeline for Uncoilable or Failed Aneurysms clinical trial.
METHODS: In our prospective, multicenter trial, 109 complex internal carotid artery (ICA) aneurysms in 107 subjects were treated with the PED. Patients were followed per a standardized protocol at 180 d and 1, 3, and 5 yr. Aneurysm occlusion, in-stent stenosis, modified Rankin Scale scores, and complications were recorded.
RESULTS: The primary endpoint of complete aneurysm occlusion at 180 d (73.6%) was previously reported. Aneurysm occlusion for those patients with angiographic follow-up progressively increased over time to 86.8% (79/91), 93.4% (71/76), and 95.2% (60/63) at 1, 3, and 5 yr, respectively. Six aneurysms (5.7%) were retreated. New serious device-related events at 1, 3, and 5 yr were noted in 1% (1/96), 3.5% (3/85), and 0% (0/81) of subjects. There were 4 (3.7%) reported deaths in our trial. Seventy-eight (96.3%) of 81 patients with 5-yr clinical follow-up had modified Rankin Scale scores ≤2. No delayed neurological deaths or hemorrhagic or ischemic cerebrovascular events were reported beyond 6 mo. No recanalization of a previously occluded aneurysm was observed.
CONCLUSION: Our 5-yr findings demonstrate that PED is a safe and effective treatment for large and giant wide-necked aneurysms of the intracranial ICA, with high rates of complete occlusion and low rates of delayed adverse events.
To evaluate the safety and effectiveness of the Pipeline Embolization Device (PED; ev3/Covidien, Irvine, Calif) in the treatment of complex intracranial aneurysms.
The Pipeline for Uncoilable or ...Failed Aneurysms is a multicenter, prospective, interventional, single-arm trial of PED for the treatment of uncoilable or failed aneurysms of the internal carotid artery. Institutional review board approval of the HIPAA-compliant study protocol was obtained from each center. After providing informed consent, 108 patients with recently unruptured large and giant wide-necked aneurysms were enrolled in the study. The primary effectiveness endpoint was angiographic evaluation that demonstrated complete aneurysm occlusion and absence of major stenosis at 180 days. The primary safety endpoint was occurrence of major ipsilateral stroke or neurologic death at 180 days.
PED placement was technically successful in 107 of 108 patients (99.1%). Mean aneurysm size was 18.2 mm; 22 aneurysms (20.4%) were giant (>25 mm). Of the 106 aneurysms, 78 met the study's primary effectiveness endpoint (73.6%; 95% posterior probability interval: 64.4%-81.0%). Six of the 107 patients in the safety cohort experienced a major ipsilateral stroke or neurologic death (5.6%; 95% posterior probability interval: 2.6%-11.7%).
PED offers a reasonably safe and effective treatment of large or giant intracranial internal carotid artery aneurysms, demonstrated by high rates of complete aneurysm occlusion and low rates of adverse neurologic events; even in aneurysms failing previous alternative treatments.
Current status of biomarkers for prostate cancer Velonas, Vicki M; Woo, Henry H; dos Remedios, Cristobal G ...
International Journal of Molecular Sciences,
05/2013, Volume:
14, Issue:
6
Journal Article, Book Review
Peer reviewed
Open access
Prostate cancer (PCa) is a leading cause of cancer-related death of men globally. Since its introduction, there has been intense debate as to the effectiveness of the prostate specific antigen (PSA) ...test as a screening tool for PCa. It is now evident that the PSA test produces unacceptably high rates of false positive results and is not prognostic. Here we review the current status of molecular biomarkers that promise to be prognostic and that might inform individual patient management. It highlights current efforts to identify biomarkers obtained by minimally invasive methods and discusses current knowledge with regard to gene fusions, mRNA and microRNAs, immunology, and cancer-associated microparticles.
OBJECTIVE The long-term effectiveness of endovascular treatment of large and giant wide-neck aneurysms using traditional endovascular techniques has been disappointing, with high recanalization and ...re-treatment rates. Flow diversion with the Pipeline Embolization Device (PED) has been recently used as a stand-alone therapy for complex aneurysms, showing significant improvement in effectiveness while demonstrating a similar safety profile to stent-supported coil treatment. However, relatively little is known about its long-term safety and effectiveness. Here the authors report on the 3-year safety and effectiveness of flow diversion with the PED in a prospective cohort of patients with large and giant internal carotid artery aneurysms enrolled in the Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial. METHODS The PUFS trial is a prospective study of 107 patients with 109 aneurysms treated with the PED. Primary effectiveness and safety end points were demonstrated based on independently monitored 180-day clinical and angiographic data. Patients were enrolled in a long-term follow-up protocol including 1-, 3-, and 5-year clinical and imaging follow-up. In this paper, the authors report the midstudy (3-year) effectiveness and safety data. RESULTS At 3 years posttreatment, 74 subjects with 76 aneurysms underwent catheter angiography as required per protocol. Overall, complete angiographic aneurysm occlusion was observed in 71 of these 76 aneurysms (93.4% cure rate). Five aneurysms were re-treated, using either coils or additional PEDs, for failure to occlude, and 3 of these 5 were cured by the 3-year follow-up. Angiographic cure with one or two treatments of Pipeline embolization alone was therefore achieved in 92.1%. No recanalization of a previously completely occluded aneurysm was noted on the 3-year angiograms. There were 3 (2.6%) delayed device- or aneurysm-related serious adverse events, none of which led to permanent neurological sequelae. No major or minor late-onset hemorrhagic or ischemic cerebrovascular events or neurological deaths were observed in the 6-month through 3-year posttreatment period. Among 103 surviving patients, 85 underwent functional outcome assessment in which modified Rankin Scale scores of 0-1 were demonstrated in 80 subjects. CONCLUSIONS Pipeline embolization is safe and effective in the treatment of complex large and giant aneurysms of the intracranial internal carotid artery. Unlike more traditional endovascular treatments, flow diversion results in progressive vascular remodeling that leads to complete aneurysm obliteration over longer-term follow-up without delayed aneurysm recanalization and/or growth. Clinical trial registration no.: NCT00777088 (clinicaltrials.gov).
Abstract Context Photoselective vaporisation (PVP) of the prostate is being used increasingly to treat symptomatic benign prostatic hyperplasia, due to the associated lower morbidity. Holmium laser ...enucleation of the prostate was considered to be the treatment with the highest evidence; however, evidence for PVP has dramatically increased recently. Objective To conduct a systematic review and meta-analysis of level 1 evidence studies to determine the effectiveness of PVP versus transurethral resection of the prostate (TURP) for surgical treatment of benign prostatic hyperplasia. Outcomes reviewed included perioperative data, complications, and functional outcomes. Evidence acquisition Biomedical databases from 2002 to 2012 and American Urological Association and European Association of Urology conference proceedings from 2007 to 2011 were searched. Trials were included if they were randomised controlled trials, had PVP as the intervention, and TURP as control. Meta-analysis was performed using a random effects model. Evidence synthesis Nine trials were identified with 448 patients undergoing PVP (80 W in five trials and 120 W in four trials) and 441 undergoing TURP. Catheterisation time and length of stay were shorter in the PVP group by 1.91 d (95% confidence interval CI, 1.47–2.35; p < 0.00001) and 2.13 d (95% CI, 1.78–2.48; p < 0.00001), respectively. Operation time was shorter in the TURP group by 19.64 min (95% CI, 9.05–30.23; p = 0.0003). Blood transfusion was significantly less likely in the PVP group (risk ratio: 0.16; 95% CI, 0.05–0.53; p = 0.003). There were no significant differences between PVP and TURP when comparing other complications. Regarding functional outcomes, six studies found no difference between PVP and TURP, two favoured TURP, and one favoured PVP. Conclusions Perioperative outcomes of catheterisation time and length of hospital stay were shorter with PVP, whereas operative time was longer with PVP. Postoperative complications of blood transfusion and clot retention were significantly less likely with PVP; no difference was noted in other complications. Overall, no difference was noted in intermediate-term functional outcomes.
Purpose
This study is a systematic analysis of the evidence regarding oncological, perioperative and postoperative outcomes and the cost of open retropubic radical prostatectomy (ORP), laparoscopic ...radical prostatectomy (LRP) and robotic-assisted laparoscopic radical prostatectomy (RALP).
Methods
Summary data was abstracted from 104 original research articles representing 227,400 patients. PubMed/Medline, Scopus, Google Scholar, EMBASE and the Cochrane Library were reviewed in December 2016. A total of 104 publications were selected for inclusion. The primary outcomes were positive surgical margin (PSM) and major complication rate according to Clavien classifications. Secondary outcomes were operative time, length of hospital stay, estimated blood loss, transfusions, conversions, rate of post-operative erectile dysfunction and incontinence and total cost of procedure.
Results
ORP had a significantly higher rate than RALP for PSM (OR: 1.18; 95% CI 1.05–1.32;
p
= 0.004), but the rate of PSM was not significantly different between ORP versus LRP (OR: 1.37; 95% CI 0.88–2.14;
p
= 0.17) and RALP versus LRP (OR: 0.83; 95% CI 0.40–1.72;
p
= 0.62). The major Clavien complication rate was significantly different between ORP and RALP (OR: 2.14; 95% CI 1.24–3.68;
p
= 0.006). Estimated blood loss, transfusions and length of hospital stay were low for RALP, moderate for LRP and high for ORP. The rate of erectile dysfunction (OR: 2.58; 95% CI 1.77–3.75;
p
< 0.001) and incontinence (OR: 3.57; 95% CI 2.28–5.58;
p
< 0.001) were significantly lower after RALP than LRP and equivalent for other comparisons. Total cost was highest for RALP, followed by LRP and ORP.
Conclusions
For PSM and peri- and post-operative complications, RALP showed better results than ORP and LRP. In the context of the biases between the studies, one should interpret the results with caution.
Adjuvant radiotherapy has been shown to halve the risk of biochemical progression for patients with high-risk disease after radical prostatectomy. Early salvage radiotherapy could result in similar ...biochemical control with lower treatment toxicity. We aimed to compare biochemical progression between patients given adjuvant radiotherapy and those given salvage radiotherapy.
We did a phase 3, randomised, controlled, non-inferiority trial across 32 oncology centres in Australia and New Zealand. Eligible patients were aged at least 18 years and had undergone a radical prostatectomy for adenocarcinoma of the prostate with pathological staging showing high-risk features defined as positive surgical margins, extraprostatic extension, or seminal vesicle invasion; had an Eastern Cooperative Oncology Group performance status of 0–1, and had a postoperative prostate-specific antigen (PSA) concentration of 0·10 ng/mL or less. Patients were randomly assigned (1:1) using a minimisation technique via an internet-based, independently generated allocation to either adjuvant radiotherapy within 6 months of radical prostatectomy or early salvage radiotherapy triggered by a PSA of 0·20 ng/mL or more. Allocation sequence was concealed from investigators and patients, but treatment assignment for individual randomisations was not masked. Patients were stratified by radiotherapy centre, preoperative PSA, Gleason score, surgical margin status, and seminal vesicle invasion status. Radiotherapy in both groups was 64 Gy in 32 fractions to the prostate bed without androgen deprivation therapy with real-time review of plan quality on all cases before treatment. The primary endpoint was freedom from biochemical progression. Salvage radiotherapy would be deemed non-inferior to adjuvant radiotherapy if freedom from biochemical progression at 5 years was within 10% of that for adjuvant radiotherapy with a hazard ratio (HR) for salvage radiotherapy versus adjuvant radiotherapy of 1·48. The primary analysis was done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT00860652.
Between March 27, 2009, and Dec 31, 2015, 333 patients were randomly assigned (166 to adjuvant radiotherapy; 167 to salvage radiotherapy). Median follow-up was 6·1 years (IQR 4·3–7·5). An independent data monitoring committee recommended premature closure of enrolment because of unexpectedly low event rates. 84 (50%) patients in the salvage radiotherapy group had radiotherapy triggered by a PSA of 0·20 ng/mL or more. 5-year freedom from biochemical progression was 86% (95% CI 81–92) in the adjuvant radiotherapy group versus 87% (82–93) in the salvage radiotherapy group (stratified HR 1·12, 95% CI 0·65–1·90; pnon-inferiority=0·15). The grade 2 or worse genitourinary toxicity rate was lower in the salvage radiotherapy group (90 54% of 167) than in the adjuvant radiotherapy group (116 70% of 166). The grade 2 or worse gastrointestinal toxicity rate was similar between the salvage radiotherapy group (16 10%) and the adjuvant radiotherapy group (24 14%).
Salvage radiotherapy did not meet trial specified criteria for non-inferiority. However, these data support the use of salvage radiotherapy as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity.
New Zealand Health Research Council, Australian National Health Medical Research Council, Cancer Council Victoria, Cancer Council NSW, Auckland Hospital Charitable Trust, Trans-Tasman Radiation Oncology Group Seed Funding, Cancer Research Trust New Zealand, Royal Australian and New Zealand College of Radiologists, Cancer Institute NSW, Prostate Cancer Foundation Australia, and Cancer Australia.
Summary Background Androgen-deprivation therapy is offered to men with prostate cancer who have a rising prostate-specific antigen after curative therapy (PSA relapse) or who are considered not ...suitable for curative treatment; however, the optimal timing for its introduction is uncertain. We aimed to assess whether immediate androgen-deprivation therapy improves overall survival compared with delayed therapy. Methods In this randomised, multicentre, phase 3, non-blinded trial, we recruited men through 29 oncology centres in Australia, New Zealand, and Canada. Men with prostate cancer were eligible if they had a PSA relapse after previous attempted curative therapy (radiotherapy or surgery, with or without postoperative radiotherapy) or if they were not considered suitable for curative treatment (because of age, comorbidity, or locally advanced disease). We used a database-embedded, dynamically balanced, randomisation algorithm, coordinated by the Cancer Council Victoria, to randomly assign participants (1:1) to immediate androgen-deprivation therapy (immediate therapy arm) or to delayed androgen-deprivation therapy (delayed therapy arm) with a recommended interval of at least 2 years unless clinically contraindicated. Randomisation for participants with PSA relapse was stratified by type of previous therapy, relapse-free interval, and PSA doubling time; randomisation for those with non-curative disease was stratified by metastatic status; and randomisation in both groups was stratified by planned treatment schedule (continuous or intermittent) and treatment centre. Clinicians could prescribe any form and schedule of androgen-deprivation therapy and group assignment was not masked. The primary outcome was overall survival in the intention-to-treat population. The trial closed to accrual in 2012 after review by the independent data monitoring committee, but data collection continued for 18 months until Feb 26, 2014. It is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12606000301561) and ClinicalTrials.gov ( NCT00110162 ). Findings Between Sept 3, 2004, and July 13, 2012, we recruited 293 men (261 with PSA relapse and 32 with non-curable disease). We randomly assigned 142 men to the immediate therapy arm and 151 to the delayed therapy arm. Median follow-up was 5 years (IQR 3·3–6·2) from the date of randomisation. 16 (11%) men died in the immediate therapy arm and 30 (20%) died in the delayed therapy arm. 5-year overall survival was 86·4% (95% CI 78·5–91·5) in the delayed therapy arm versus 91·2% (84·2–95·2) in the immediate therapy arm (log-rank p=0·047). After Cox regression, the unadjusted HR for overall survival for immediate versus delayed arm assignment was 0·55 (95% CI 0·30–1·00; p=0·050). 23 patients had grade 3 treatment-related adverse events. 105 (36%) men had adverse events requiring hospital admission; none of these events were attributable to treatment or differed between treatment-timing groups. The most common serious adverse events were cardiovascular, which occurred in nine (6%) patients in the delayed therapy arm and 13 (9%) in the immediate therapy arm. Interpretation Immediate receipt of androgen-deprivation therapy significantly improved overall survival compared with delayed intervention in men with PSA-relapsed or non-curable prostate cancer. The results provide benchmark evidence of survival rates and morbidity to discuss with men when considering their treatment options. Funding Australian National Health and Medical Research Council and Cancer Councils, The Royal Australian and New Zealand College of Radiologists, Mayne Pharma Australia.
Multiparametric magnetic resonance imaging (MRI) is validated for the detection of clinically significant prostate cancer (csPCa), although patients with negative/equivocal MRI undergo biopsy for ...false negative concerns. In addition, 68Ga-PSMA-11 positron emission tomography/computed tomography (prostate-specific membrane antigen PSMA) may also identify csPCa accurately.
This trial aimed to determine whether the combination of PSMA + MRI was superior to MRI in diagnostic performance for detecting csPCa.
A prospective multicentre phase II imaging trial was conducted. A total of 296 men were enrolled with suspected prostate cancer, with no prior biopsy or MRI, recent MRI (6 mo), and planned transperineal biopsy based on clinical risk and MRI. In all, 291 men underwent MRI, pelvic-only PSMA, and systematic ± targeted biopsy.
Sensitivity, specificity, and predictive values (negative predictive value NPV and positive predictive value) for csPCa were determined for MRI, PSMA, and PSMA + MRI. PSMA + MRI was defined as negative for PSMA negative Prostate Imaging Reporting and Data System (PI-RADS) 2/3 and positive for either MRI PI-RADS 4/5 or PSMA positive PI-RADS 2/3; csPCa was any International Society of Urological Pathology (ISUP) grade group ≥2 malignancy.
Of the patients, 56% (n = 162) had csPCa; 67% had PI-RADS 3–5, 73% were PSMA positive, and 81% were combined PSMA + MRI positive. Combined PSMA + MRI improved NPV compared with MRI alone (91% vs 72%, test ratio = 1.27 1.11–1.39, p < 0.001). Sensitivity also improved (97% vs 83%, p < 0.001); however, specificity was reduced (40% vs 53%, p = 0.011). Five csPCa cases were missed with PSMA + MRI (four ISUP 2 and one ISUP 3). Of all men, 19% (56/291) were PSMA + MRI negative (38% of PI-RADS 2/3) and could potentially have avoided biopsy, risking delayed csPCa detection in 3.1% men with csPCa (5/162) or 1.7% (5/291) overall.
PSMA + MRI improved NPV and sensitivity for csPCa in an MRI triaged population. Further randomised studies will determine whether biopsy can safely be omitted in men with a high clinical suspicion of csPCa but negative combined imaging.
The combination of magnetic resonance imaging (MRI) + prostate-specific membrane antigen positron emission tomography reduces false negatives for clinically significant prostate cancer (csPCa) compared with MRI, potentially allowing a reduction in the number of prostate biopsies required to diagnose csPCa.
The combination of magnetic resonance imaging (MRI) and prostate-specific membrane antigen (PSMA) improves the detection of significant malignancy compared with MRI or PSMA alone. This may allow further reduction in prostate biopsies required to diagnose prostate cancer using MRI.
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