Vascular targeted photochemotherapy using padoporfin and padeliporfin as a method of the focal treatment of localised prostate cancer - clinician's insight.
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ABSTRACT:
SUBMITTER: Bugaj AM
PROVIDER: S-EPMC4804253 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
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Vascular targeted photochemotherapy using padoporfin and padeliporfin as a method of the focal treatment of localised prostate cancer - clinician's insight.
World journal of methodology 20160326 1
Vascular targeted photochemotherapy (VTP) holds promise as a novel strategy of the focal treatment of localised prostate cancer (LPCa). It is convenient to perform, minimally invasive and can be conduct in ambulatory conditions. In this review, methodologic aspects of padoporfin- and padeliporfin-mediated VTP and its clinical application in focal treatment of LPCa as well as future perspective of this method were presented. Physicochemical and pharmacokinetic parameters of padoporphin and padeli ...[more]
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Project description:BACKGROUND:Radical whole-gland therapy can lead to significant genitourinary and rectal side-effects for men with localised prostate cancer. We report on whether selective focal ablation of unifocal and multifocal cancer lesions can reduce this treatment burden. METHODS:Men aged 45-80 years were eligible for this prospective development study if they had low-risk to high-risk localised prostate cancer (prostate specific antigen [PSA] ?15 ng/mL, Gleason score ?4?+?3, stage ?T2), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI and have a general anaesthetic. Patients received focal therapy using high-intensity focused ultrasound, delivered to all known cancer lesions, with a margin of normal tissue, identified on multiparametric MRI, template prostate-mapping biopsies, or both. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. Analyses were done on a per-protocol basis. This study is registered with ClinicalTrials.gov, number NCT00561314. FINDINGS:42 men were recruited between June 27, 2007, and June 30, 2010; one man died from an unrelated cause (pneumonia) 3 months after treatment and was excluded from analyses. After treatment, one man was admitted to hospital for acute urinary retention, and another had stricture interventions requiring hospital admission. Nine men (22%, 95% CI 11-38) had self-resolving, mild to moderate, intermittent dysuria (median duration 5·0 days [IQR 2·5-18·5]). Urinary debris occurred in 14 men (34%, 95% CI 20-51), with a median duration of 14·5 days (IQR 6·0-16·5). Urinary tract infection was noted in seven men (17%, 95% CI 7-32). Median overall International Index of Erectile Function-15 (IIEF-15) scores were similar at baseline and at 12 months (p=0·060), as were median IIEF-15 scores for intercourse satisfaction (p=0·454), sexual desire (p=0·644), and overall satisfaction (p=0·257). Significant deteriorations between baseline and 12 months were noted for IIEF-15 erectile (p=0·042) and orgasmic function (p=0·003). Of 35 men with good baseline function, 31 (89%, 95% CI 73-97) had erections sufficient for penetration 12 months after focal therapy. Median UCLA Expanded Prostate Cancer Index Composite (EPIC) urinary incontinence scores were similar at baseline as and 12 months (p=0·045). There was an improvement in lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), between baseline and 12 months (p=0·026), but the IPSS-quality of life score showed no difference between baseline and 12 months (p=0·655). All 38 men with no baseline urinary incontinence were leak-free and pad-free by 9 months. All 40 men pad-free at baseline were pad-free by 3 months and maintained pad-free continence at 12 months. No significant difference was reported in median Trial Outcomes Index scores between baseline and 12 months (p=0·113) but significant improvement was shown in median Functional Assessment of Cancer Therapy (FACT)-Prostate (p=0·045) and median FACT-General scores (p=0·041). No histological evidence of cancer was identified in 30 of 39 men biopsied at 6 months (77%, 95% CI 61-89); 36 (92%, 79-98) were free of clinically significant cancer. After retreatment in four men, 39 of 41 (95%, 95% CI 83-99) had no evidence of disease on multiparametric MRI at 12 months. INTERPRETATION:Focal therapy of individual prostate cancer lesions, whether multifocal or unifocal, leads to a low rate of genitourinary side-effects and an encouraging rate of early absence of clinically significant prostate cancer. FUNDING:Medical Research Council (UK), Pelican Cancer Foundation, and St Peters Trust.
| S-EPMC3366323 | biostudies-literature
Project description:Although radiotherapy to the prostate for cancer is effective, recurrence occurs in 10-15% within 5 years. Traditional salvage treatments for men with radiorecurrent prostate cancer comprise of watchful waiting (WW) with or without androgen deprivation therapy (ADT) or radical prostatectomy (RP). Neither strategy provides ideal therapeutic ratios. Salvage focal ablation is an emerging option. We performed a systematic review of the Medline and Embase databases for studies reporting outcomes of focal salvage brachytherapy (sBT), cryotherapy (sCT) or high-intensity focused ultrasound (sHIFU) for radiorecurrent prostate cancer (conception to April 2019). Results were screened for inclusion against predetermined eligibility criteria. Certain data were extracted, including rates of biochemical disease-free survival (BDFS), metastasis, conversion to second-line therapies and adverse events. Of a total 134 articles returned from the search, 15 studies (14 case series and 1 comparative study) reported outcomes after focal sBT [5], sCT [7] and sHIFU [3]. Cohort size varied depending on intervention, with eligible studies of sBT being small case series. Median follow-up ranged from 10 to 56 months. Although pre-salvage demographics were similar [median age range, 61-75 years; prostate-specific antigen (PSA) range, 2.8-5.5 ng/mL], there was heterogeneity in patient selection, individual treatment protocols and outcome reporting. At 3 years, BDFS ranged from 61% to 71.4% after sBT, 48.1-72.4% after sCT and 48% after sHIFU. Only studies of sCT reported 5-year BDFS, which ranged from 46.5% to 54.4%. Rates of metastasis were low after all salvage modalities, as were conversion to second-line therapies (although this was poorly reported). Grade 3 adverse events were rare. This systematic review indicates that salvage focal ablation of radiorecurrent prostate cancer provides acceptable oncological outcomes and is well tolerated. Unfortunately, there is heterogeneity in the study design of existing evidence. Level 1 research comparing salvage focal therapies to existing whole-gland strategies is needed to further establish the role of these promising treatments.
| S-EPMC7354313 | biostudies-literature
Project description:BackgroundRecurrent prostate cancer after radiotherapy occurs in one in five patients. The efficacy of prostate magnetic resonance imaging (MRI) in recurrent cancer has not been established. Furthermore, high-quality data on new minimally invasive salvage focal ablative treatments are needed.ObjectiveTo evaluate the role of prostate MRI in detection of prostate cancer recurring after radiotherapy and the role of salvage focal ablation in treating recurrent disease.Design, setting, and participantsThe FORECAST trial was both a paired-cohort diagnostic study evaluating prostate multiparametric MRI (mpMRI) and MRI-targeted biopsies in the detection of recurrent cancer and a cohort study evaluating focal ablation at six UK centres. A total of 181 patients were recruited, with 155 included in the MRI analysis and 93 in the focal ablation analysis.InterventionPatients underwent choline positron emission tomography/computed tomography and a bone scan, followed by prostate mpMRI and MRI-targeted and transperineal template-mapping (TTPM) biopsies. MRI was reported blind to other tests. Those eligible underwent subsequent focal ablation. An amendment in December 2014 permitted focal ablation in patients with metastases.Outcome measurements and statistical analysisPrimary outcomes were the sensitivity of MRI and MRI-targeted biopsies for cancer detection, and urinary incontinence after focal ablation. A key secondary outcome was progression-free survival (PFS).Results and limitationsStaging whole-body imaging revealed localised cancer in 128 patients (71%), with involvement of pelvic nodes only in 13 (7%) and metastases in 38 (21%). The sensitivity of MRI-targeted biopsy was 92% (95% confidence interval [CI] 83-97%). The specificity and positive and negative predictive values were 75% (95% CI 45-92%), 94% (95% CI 86-98%), and 65% (95% CI 38-86%), respectively. Four cancer (6%) were missed by TTPM biopsy and six (8%) were missed by MRI-targeted biopsy. The overall MRI sensitivity for detection of any cancer was 94% (95% CI 88-98%). The specificity and positive and negative predictive values were 18% (95% CI 7-35%), 80% (95% CI 73-87%), and 46% (95% CI 19-75%), respectively. Among 93 patients undergoing focal ablation, urinary incontinence occurred in 15 (16%) and five (5%) had a grade ≥3 adverse event, with no rectal injuries. Median follow-up was 27 mo (interquartile range 18-36); overall PFS was 66% (interquartile range 54-75%) at 24 mo.ConclusionsPatients should undergo prostate MRI with both systematic and targeted biopsies to optimise cancer detection. Focal ablation for areas of intraprostatic recurrence preserves continence in the majority, with good early cancer control.Patient summaryWe investigated the role of magnetic resonance imaging (MRI) scans of the prostate and MRI-targeted biopsies in outcomes after cancer-targeted high-intensity ultrasound or cryotherapy in patients with recurrent cancer after radiotherapy. Our findings show that these patients should undergo prostate MRI with both systematic and targeted biopsies and then ablative treatment focused on areas of recurrent cancer to preserve their quality of life. This trial is registered at ClinicalTrials.gov as NCT01883128.
| S-EPMC9156577 | biostudies-literature
Project description: Not available
| S-EPMC7270852 | biostudies-literature
Project description:ObjectivesTo assess the patient preferences and utility scores for the different conventional and innovative treatment modalities for localised prostate cancer (PCa).Subjects and methodsPatients treated for localised PCa and healthy volunteers were invited to fill out a treatment-outcome scenario questionnaire. Participants ranked six different treatments for localised PCa from most to least favourable, prior to information. In a next step, treatment procedures, toxicity, risk of biochemical recurrence and follow-up regimen were comprehensibly described for each of the six treatments (i.e. treatment-outcome scenarios), after which patients re-ranked the six treatments. Additionally, participants gave a visual analogue scale (VAS) and time trade-off (TTO) score for each scenario. Differences between utility scores were tested by Friedman tests with post hoc Wilcoxon signed-rank tests.ResultsEighty patients and twenty-nine healthy volunteers were included in the study. Before receiving treatment-outcome scenario information, participants ranked magnetic resonance-guided adaptive radiotherapy most often as their first choice (35%). After treatment information was received, active surveillance was most often ranked as the first choice (41%). Utility scores were significantly different between the six treatment-outcome scenarios, and active surveillance, non- and minimal-invasive treatments received higher scores.ConclusionsActive surveillance and non-invasive treatment for localised PCa were the most preferred options by PCa patients and healthy volunteers and received among the highest utility scores. Treatment preferences change after treatment information is received.
| S-EPMC9931535 | biostudies-literature
Project description:BackgroundContemporary screening for prostate cancer frequently identifies small volume, low-grade lesions. Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions. To identify which patients might benefit from focal ablative techniques, we analysed the surgical specimens of a large sample of population-detected men undergoing radical prostatectomy as part of a randomised clinical trial.MethodsSurgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume, location and grade. These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately.ResultsSolitary cancers were found in prostatectomy specimens from 19% (100 out of 525) of men. In addition, 73 out of 425 (17%) men had multiple cancers with a solitary significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially suitable for focal therapy. The majority of these were small, well-differentiated lesions that appeared to be pathologically insignificant (38-66%). Criteria used to select patients for focal prostatic ablation underestimated the cancer's significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions.ConclusionFocal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer. Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone. Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression.
| S-EPMC3185935 | biostudies-literature
Project description:ContextThe incidence of localised prostate cancer is increasing worldwide. In light of recent evidence, current, radical, whole-gland treatments for organ-confined disease have being questioned with respect to their side effects, cancer control, and cost. Focal therapy may be an effective alternative strategy.ObjectiveTo systematically review the existing literature on baseline characteristics of the target population; preoperative evaluation to localise disease; and perioperative, functional, and disease control outcomes following focal therapy.Evidence acquisitionMedline (through PubMed), Embase, Web of Science, and Cochrane Review databases were searched from inception to 31 October 2012. In addition, registered but not yet published trials were retrieved. Studies evaluating tissue-preserving therapies in men with biopsy-proven prostate cancer in the primary or salvage setting were included.Evidence synthesisA total of 2350 cases were treated to date across 30 studies. Most studies were retrospective with variable standards of reporting, although there was an increasing number of prospective registered trials. Focal therapy was mainly delivered to men with low and intermediate disease, although some high-risk cases were treated that had known, unilateral, significant cancer. In most of the cases, biopsy findings were correlated to specific preoperative imaging, such as multiparametric magnetic resonance imaging or Doppler ultrasound to determine eligibility. Follow-up varied between 0 and 11.1 yr. In treatment-naïve prostates, pad-free continence ranged from 95% to 100%, erectile function ranged from 54% to 100%, and absence of clinically significant cancer ranged from 83% to 100%. In focal salvage cases for radiotherapy failure, the same outcomes were achieved in 87.2-100%, 29-40%, and 92% of cases, respectively. Biochemical disease-free survival was reported using a number of definitions that were not validated in the focal-therapy setting.ConclusionsOur systematic review highlights that, when focal therapy is delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short- to medium-term follow-up. Focal therapy is a strategy by which the overtreatment burden of the current prostate cancer pathway could be reduced, but robust comparative effectiveness studies are now required.
| S-EPMC4179888 | biostudies-literature
Project description:IntroductionFocal therapy has emerged as a promising treatment option for men with localised prostate cancer. However, most of the evaluation of postoperative function has taken place at a relatively high, non-granular level. Most of the data we use to provide informed consent for our patients is obtained from retrospective series, or derived from prospective studies whose primary outcome was oncological. Finally, most studies have focused on erectile function and overlooked other, presumably important, elements of male sexual function. The present study aims at studying in-depth the sexual consequences of focal therapy with various energy sources.Methods and analysisThis will be a mixed-methods research study based on a retrospective and prospective cohort, recruited in parallel. The retrospective cohort will consist of patients treated with focal irreversible electroporation, and the prospective cohort of patients treated with three focal therapy energies. Participants will be recruited from two UK urology centres, one National Health Service and one private. On consent, patients will fill in self-administered validated questionnaires (International Index of Erectile Function-15 (IIEF-15), Male Sexual Health Questionnaire-Ejaculatory Dysfunction-Short Form (MSHQ-EjD-SF)) and semistructured interviews will be organised to collect patients' expectations and postoperative changes in domains such as erection, ejaculation, orgasm, libido/sexual desire, masculinity/virility, penile morphology, pain or discomfort, regret, shame, cancer-related stress, overall impact and partner satisfaction. An exploratory thematic analysis will be performed to detail recurring themes that will be grouped into clusters of experiences. We will then be able to find clusters of agreement and disagreement that will be illustrated using exemplar patient quotations.Ethics and disseminationEthical approval was obtained (Regional Ethics Committee reference 20/NW/0335), as well as Health Research Authority approval. Results will be published in open-access peer-reviewed journals. Findings will also be translated into patient information resources (leaflets, online information sheets).Trial registration numberISRCTN11634296; Pre-results.
| S-EPMC7745515 | biostudies-literature
Project description:IntroductionFocal therapy may reduce the toxicity of current radical treatments while maintaining the oncological benefit. Irreversible electroporation (IRE) has been proposed to be tissue selective and so might have favourable characteristics compared to the currently used prostate ablative technologies. The aim of this trial is to determine the adverse events, genito-urinary side effects and early histological outcomes of focal IRE in men with localised prostate cancer.MethodsThis is a single centre prospective development (stage 2a) study following the IDEAL recommendations for evaluating new surgical procedures. Twenty men who have MRI-visible disease localised in the anterior part of the prostate will be recruited. The sample size permits a precision estimate around key functional outcomes. Inclusion criteria include PSA ≤ 15 ng/ml, Gleason score ≤ 4 + 3, stage T2N0M0 and absence of clinically significant disease outside the treatment area. Treatment delivery will be changed in an adaptive iterative manner so as to allow optimisation of the IRE protocol. After focal IRE, men will be followed during 12 months using validated patient reported outcome measures (IPSS, IIEF-15, UCLA-EPIC, EQ-5D, FACT-P, MAX-PC). Early disease control will be evaluated by mpMRI and targeted transperineal biopsy of the treated area at 6 months.DiscussionThe NEAT trial will assess the early functional and disease control outcome of focal IRE using an adaptive design. Our protocol can provide guidance for designing an adaptive trial to assess new surgical technologies in the challenging landscape of health technology assessment in prostate cancer treatment.
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Project description:Vascular anomalies comprise an array of congenital developmental disorders that can lead to significant disfigurement and physiologic disarray. The vast multitude of clinical phenotypes has inherently led to misdiagnosis and patients and families enduring long diagnostic odysseys of medical care. Although the observed variation in disease manifestations remains poorly understood, targeted next-generation sequencing has pivoted our understanding of the pathobiology of vascular anomalies and, for the first time, uncovered potential pharmacologic targets for these disorders. In this review article, we highlight current and developing targeted therapies for vascular anomalies, namely phosphoinositide 3-kinase and mitogen-activated protein kinase pathway inhibitors, and discuss the future directions of targeted therapies.
| S-EPMC8721128 | biostudies-literature