Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial

Lane, J. Athene; Donovan, Jenny; Davis, Michael J.; Walsh, Eleanor; Dedman, Daniel; Down, L; Turner, Emma L; Mason, Malcolm David; Metcalfe, Chris; Peters, Tim J.; Martin, Richard M.; Neal, David E.; Hamdy, Freddie C.

doi:10.1016/s1470-2045(14)70361-4

Cited by 208 publications

(198 citation statements)

References 35 publications

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“…This trial is a primary-care based cluster-randomized trial of a single PSA test, 14 within which the ProtecT trial of treatments for localized prostate cancer was embedded 15 (Supplementary Figure S1). Between 2001 and 2009, 785 eligible general practices around 8 hospital centers in England and Wales were randomized before recruitment ('Zelen' design) to intervention-or control-groups and approached for consent to participate.…”

Section: Randomizationmentioning

confidence: 99%

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality

Martin

Donovan

Turner

et al. 2018

JAMA

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352

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms cancer was higher in the intervention (4.3%) group than control (3.6%) group, but there was no significant difference in prostate cancer mortality (intervention, 0.29% vs. control, 0.29%) after a median follow-up of 10-years. Meaning:The CAP single PSA-screen intervention detected more prostate cancer cases, but after a median of 10-years' follow-up has, thus far, had no significant effect on prostate cancer mortality. Conclusion and relevance:Among practices randomized to a low-intensity PSA screening intervention compared with standard practice, there was no significant difference in prostate cancer mortality after a 4 median 10-years follow up, but the detection of low-risk prostate cancers increased. Although longer-term follow-up is in progress, the current findings do not support single PSA-testing for population-based screening.

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Section: Randomizationmentioning

confidence: 99%

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality

Martin

Donovan

Turner

et al. 2018

JAMA

Self Cite

352

325

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“…These challenges are very likely to be encountered in a RCT comparing focal therapy to a standard option in light of the different toxicity profiles of the two arms, as well as the debate surrounding the legitimacy of focal therapy among clinicians. If such trial would be revealed unfeasible, an alternative way of randomization should be explored -such as what the researchers have applied within the ProtecT trial -or alternative trial designs should be considered in order to evaluate in a rigorous and timely manner a focal therapy option (51). Cancer control in studies with intention to treat is encouraging, although this needs to be verified against standard of care in high quality comparative effectiveness trials.…”

Section: Brachytherapymentioning

confidence: 99%

New and Established Technology in Focal Ablation of the Prostate: A Systematic Review

et al. 2017

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Word Count (text): 4,713Keywords: focal therapy, partial ablation, prostate cancer 2 ABSTRACT Context: focal therapy of prostate cancer has been proposed as an alternative to wholegland treatments.Objective: to summarise the evidence regarding sources of energy employed in focal therapy.Evidence Acquisition: Embase and Medline (PubMed) were searched from 1996 to 31 st October 2015 following the PRISMA statement. Ongoing trials were selected from electronic registries.Evidence Synthesis: thirty-seven articles reporting on 3,230 patients undergoing focal therapy were selected. 13 reported on high intensity focused ultrasound (HIFU), 11 on cryotherapy, three on photodynamic therapy (PDT), four on laser interstitial thermotherapy (LITT), two on brachytherapy, three on irreversible electroporation (IRE), and one on radiofrequency (RFA). HIFU, cryotherapy, PDT and brachytherapy have been assessed in up to stage 2b studies. LITT and IRE have been evaluated in up to stage 2a studies. RFA has been evaluated in one stage 1 study. Median follow-up varied between 4-61 months, and median rate of serious adverse events ranged between 0-10.6%. Pad-free leak-free continence and potency were obtained in 83.3-100% and 81.5-100%, respectively. In series with intentionto-treat, the median rate of significant and insignificant disease at control biopsy varied between 0-13.4% and 5.1-45.9%, respectively. Main limitations are the length of follow-up, the absence of a comparator arm, and study heterogeneity.Conclusion: focal therapy has been evaluated using seven sources of energy in single-arm retrospective and prospective development studies up to stage 2b. Focal therapy seems to 3 have minor impact on quality of life and genito-urinary function. Cancer-control is encouraging, although this needs to be verified in high quality comparative effectiveness studies.Patient summary: seven sources of energy have been employed to selectively ablate discrete areas of prostate cancer. There is high evidence that focal therapy is safe and has low detrimental impact on continence and potency. The oncological outcome has yet to be evaluated against standard of care.

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“…90 An RCT comparing watchful waiting with radical prostatectomy is ongoing in the United Kingdom. 13,91 Taken together, therefore, these data show that benefits from improvements in prostate cancer risk prediction, screening, and prognostic stratification will depend to a large extent on clearer evidence that surveillance, diagnostic, and treatment strategies in themselves lead to reductions in morbidity and mortality.…”

Section: Discussionmentioning

confidence: 97%

Multigene panels in prostate cancer risk assessment: a systematic review

Little

Wilson

Carter

et al. 2016

Genetics in Medicine

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Prostate cancer is the fourth most common malignancy worldwide, and the second most common among men.1 In 2014, it was estimated that more than a quarter of a million new cases were diagnosed in North America and that the disease accounted for more than 33,000 deaths. 2,3 These numbers are likely to increase with the aging of the population. On the basis of data from the Surveillance, Epidemiology, and End Results program, more men were diagnosed with prostate cancer at a younger age and earlier stage in 2004-2005 than in the mid-late 1990s, and disparity between ethnic groups in cancer stage at diagnosis decreased. 4 Apart from age, 5 ethnic group, 5,6 and family history, 7-9 the risk factors associated with prostate cancer are unclear, 5 making primary prevention difficult. Prostate cancer is currently considered to be a complex, multifactorial disease, and the vast majority of familial clustering is attributed to the interaction of multiple shared susceptibility genes with moderate to low penetrance and shared environmental factors within these families.The natural history of prostate cancer is highly variable. 10 In a large proportion of men the disease is indolent, and it is difficult to predict which tumors will be aggressive. The value of aggressive management for localized prostate cancer is debated, [11][12][13][14] and only a small proportion of men with early-stage prostate cancer die from the disease within 10 to 15 years of diagnosis. Developing tools to differentiate aggressive and indolent disease is of key importance.Prostate-specific antigen (PSA) screening was introduced in the late 1980s.15 Meta-analyses of seven randomized controlled trials (RCTs) of screening using PSA testing alone or in combination with digital rectal examination suggested no evidence of benefit in reducing mortality 16,17 and some evidence of harm from overdiagnosis.17 Amid substantial debate, 18-20 the argument has been made for developing more accurate screening tests, including possible genetic markers. Purpose: Single-nucleotide polymorphism (SNP) panel tests have been proposed for use in the detection of, and prediction of risk for, prostate cancer and as prognostic indicator in affected men. A systematic review was undertaken to address three research questions to evaluate the analytic validity, clinical validity, clinical utility, and prognostic validity of SNP-based panels.Methods: Data sources comprised MEDLINE, Cochrane CEN-TRAL, Cochrane Database of Systematic Reviews, and EMBASE; these were searched from inception to April 2013. The gray-literature searches included contact with manufacturers. Eligible studies included English-language studies evaluating commercially available SNP panels. Study selection and risk of bias assessment were undertaken by two independent reviewers. Results:Twenty-one studies met eligibility criteria. All focused on clinical validity and evaluated 18 individual panels with 2 to 35 SNPs.All had poor discriminative ability (overall area under receiver-operator characteristic curves, 5...

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Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial

Abstract: UK National Institute for Health Research Health Technology Assessment Programme.

Cited by 208 publications

References 35 publications

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality

New and Established Technology in Focal Ablation of the Prostate: A Systematic Review

Multigene panels in prostate cancer risk assessment: a systematic review

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