Dataset Information

Suitability of PSA-detected localised prostate cancers for focal therapy: experience from the ProtecT study.

ABSTRACT: Contemporary 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.Surgical 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.Solitary 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.Focal 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.

SUBMITTER: Catto JW

PROVIDER: S-EPMC3185935 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Suitability of PSA-detected localised prostate cancers for focal therapy: experience from the ProtecT study.

Catto J W F JW Robinson M C MC Albertsen P C PC Goepel J R JR Abbod M F MF Linkens D A DA Davis M M Rosario D J DJ Warren A Y AY Varma M M Griffiths D F DF Grigor K M KM Mayer N J NJ Oxley J D JD Deshmukh N S NS Lane J A JA Metcalfe C C Donovan J L JL Neal D E DE Hamdy F C FC

British journal of cancer 20110823 7

<h4>Background</h4>Contemporary 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.<h4>Methods</h4>Surgical s ...[more]

PMID: 21863028

Similar Datasets

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.

Project description:The 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.To 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.Medline (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.A 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.Our 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.

Project description:IntroductionThis study is to evaluate biochemical response, acute toxicity and health-related quality-of-life (QOL) outcomes among prostate cancer patients following stereotactic body radiation therapy (SBRT) in the first Australian CyberKnife facility.MethodsForty-five consecutive patients with clinically localised prostate cancer were treated with SBRT using CyberKnife technology and enrolled in this study. Protocol treatment consisted of 36.25 Gy in five fractions. PSA and acute toxicity was assessed at each follow-up visit and QOL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Global Health Status (GHS) C30 and PR25 questionnaires and the Karnofsky Performance Status (KPS). Distance of travel for treatment was recorded.ResultsThe median prostate-specific antigen (PSA) level declined from the initial value of 6.9 ng/mL to 1.5 ng/mL at 6 months and 0.6 ng/mL at 18 months post-treatment. Results were similar in patients who did not receive hormone therapy. Acute grade 1 gastrointestinal (GI) and genitourinary (GU) toxicities were found in 11.1% and 24.4% of patients respectively. Acute grade 2 GI and GU toxicities were found in 2.2% and 11.1% of patients respectively. There were no grade 3 and grade 4 toxicities. Mean urinary symptom score was 14.8 at baseline, 17.2 at 6 weeks and 18.3 at 6 months (P > 0.05). Mean bowel symptom score was 2.7 at baseline, 4.2 at 6 weeks and 6.3 at 6 months (P > 0.05). The mean GHS score improved from 81.3 at baseline to 82.4 at 6 weeks, and was 75.6 at 6 months (P > 0.05, not significant). Compared to baseline KPS, there was a significant mean decrease from baseline of 96.7 to 93.3 at the 6-week follow-up (P = 0.0043), which then recovered to 94.3 at the 6-month follow-up (P = 0.1387).ConclusionsEarly results show promising PSA response. Acute toxicity seemed comparable to results from conventionally fractionated radiotherapy and to international prostate SBRT studies. EORTC PR25 and C30 scores did not reveal any significant change from baseline, and although there was a decrease in KPS, the absolute decrease was small.

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.

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.

Project description:ObjectiveTo investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making.Patients and methodsMen aged 50-69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores.ResultsTreatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL.ConclusionTreatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes.

Dataset Information

Suitability of PSA-detected localised prostate cancers for focal therapy: experience from the ProtecT study.

Publications

Suitability of PSA-detected localised prostate cancers for focal therapy: experience from the ProtecT study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets