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Search: WFRF:(Freedland Stephen J)

  • Result 1-9 of 9
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  • Donovan, Michael J., et al. (author)
  • Personalized prediction of tumor response and cancer progression on prostate needle biopsy
  • 2009
  • In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 182:1, s. 125-132
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To our knowledge in patients with prostate cancer there are no available tests except clinical variables to determine the likelihood of disease progression. We developed a patient specific, biology driven tool to predict outcome at diagnosis. We also investigated whether biopsy androgen receptor levels predict a durable response to therapy after secondary treatment. MATERIALS AND METHODS: We evaluated paraffin embedded prostate needle biopsy tissue from 1,027 patients with cT1c-T3 prostate cancer treated with surgery and followed a median of 8 years. Machine learning was done to integrate clinical data with biopsy quantitative biometric features. Multivariate models were constructed to predict disease progression with the C index to estimate performance. RESULTS: In a training set of 686 patients (total of 87 progression events) 3 clinical and 3 biopsy tissue characteristics were identified to predict clinical progression within 8 years after prostatectomy with 78% sensitivity, 69% specificity, a C index of 0.74 and a HR of 5.12. Validation in an independent cohort of 341 patients (total of 44 progression events) yielded 76% sensitivity, 64% specificity, a C index of 0.73 and a HR of 3.47. Increased androgen receptor in tumor cells in the biopsy highly significantly predicted resistance to therapy, ie androgen ablation with or without salvage radiotherapy, and clinical failure (p <0.0001). CONCLUSIONS: Morphometry reliably classifies Gleason pattern 3 tumors. When combined with biomarker data, it adds to the hematoxylin and eosin analysis, and prostate specific antigen values currently used to assess outcome at diagnosis. Biopsy androgen receptor levels predict the likelihood of a response to therapy after recurrence and may guide future treatment decisions.
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  • Carter, H Ballentine, et al. (author)
  • Early detection of prostate cancer : AUA Guideline
  • 2013
  • In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 190:2, s. 419-426
  • Journal article (peer-reviewed)abstract
    • PURPOSE:The guideline purpose is to provide the urologist with a framework for the early detection of prostate cancer in asymptomatic average risk men.MATERIALS AND METHODS:A systematic review was conducted and summarized evidence derived from over 300 studies that addressed the predefined outcomes of interest (prostate cancer incidence/mortality, quality of life, diagnostic accuracy and harms of testing). In addition to the quality of evidence, the panel considered values and preferences expressed in a clinical setting (patient-physician dyad) rather than having a public health perspective. Guideline statements were organized by age group in years (age <40; 40 to 54; 55 to 69; ≥ 70).RESULTS:Except prostate specific antigen-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests. The quality of evidence for the benefits of screening was moderate, and evidence for harm was high for men age 55 to 69 years. For men outside this age range, evidence was lacking for benefit, but the harms of screening, including over diagnosis and overtreatment, remained. Modeled data suggested that a screening interval of two years or more may be preferred to reduce the harms of screening.CONCLUSIONS:The Panel recommended shared decision-making for men age 55 to 69 years considering PSA-based screening, a target age group for whom benefits may outweigh harms. Outside this age range, PSA-based screening as a routine could not be recommended based on the available evidence.
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  • Trinh, Quoc-Dien, et al. (author)
  • A Systematic Review of the Volume-Outcome Relationship for Radical Prostatectomy
  • 2013
  • In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 64:5, s. 786-798
  • Research review (peer-reviewed)abstract
    • Context: Due to the complexity and challenging nature of radical prostatectomy (RP), it is likely that both short-and long-term outcomes strongly depend on the cumulative number of cases performed by the surgeon as well as by the hospital. Objective: To review systematically the association between hospital and surgeon volume and perioperative, oncologic, and functional outcomes after RP. Evidence acquisition: A systematic review of the literature was performed, searching PubMed, Embase, and Scopus databases for original and review articles between January 1, 1995, and December 31, 2011. Inclusion and exclusion criteria comprised RP, hospital and/or surgeon volume reported as a predictor variable, a measurable end point, and a description of multiple hospitals or surgeons. Evidence synthesis: Overall 45 publications fulfilled the inclusion criteria, where most data originated from retrospective institutional or population-based cohorts. Studies generally focused on hospital or surgeon volume separately. Although most of these analyses corroborated the impact of increasing volume with better outcomes, some failed to find any significant effect. Studies also differed with respect to the proposed volume cut-off for improved outcomes, as well as the statistical means of evaluating the volume-outcome relationship. Five studies simultaneously compared hospital and surgeon volume, where results suggest that the importance of either hospital or surgeon volume largely depends on the end point of interest. Conclusions: Undeniable evidence suggests that increasing volume improves outcomes. Although it would seem reasonable to refer RP patients to high-volume centers, such regionalization may not be entirely practical. As such, the implications of such a shift in practice have yet to be fully determined and warrant further exploration. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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  • Auprich, Marco, et al. (author)
  • Contemporary Role of Prostate Cancer Antigen 3 in the Management of Prostate Cancer
  • 2011
  • In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 60:5, s. 1045-1054
  • Research review (peer-reviewed)abstract
    • Context: Newly discovered biomarkers ideally should prove clinical usefulness, provide additional detection, staging, and prognosis information to improve individual risk assessment, and potentially permit targeted cancer therapy. Objective: To review, display, and evaluate the current evidence regarding the biologic and analytic approach of urinary prostate cancer gene 3 (PCA3) in prostate cancer (PCa) detection, staging, and prognosis, and its therapeutic potential. Evidence acquisition: A systematic and comprehensive Medline search was performed using the Medical Subject Headings search terms PCA3, DD3, UPM3, prostate cancer, cell-lines, prostate tissue, prostate biopsy, detection, diagnosis, radical prostatectomy, staging, grading, progression, and gene therapy. Results were restricted to English-language papers published within the period 1999-2011. Evidence synthesis: The PCA3 gene is highly overexpressed in specific PCa cell lines and prostatic tumours. In 2006, a simple and robust urine test (Progensa) became commercially available. Despite its costs, prostate cancer antigen 3 (PCA3) is superior to prostate-specific antigen (PSA) and percent free PSA in the early detection of PCa. PCA3 improves the diagnostic accuracy of externally validated nomograms among men with an elevated PSA undergoing biopsy. PCA3 independently predicts low-volume disease and pathologically insignificant PCa but is not associated with locally advanced disease and is limited in the prediction of aggressive cancer. Preliminary data demonstrate that combining PCA3 with other new biomarkers further improves diagnostic and prognostic accuracy. Finally, findings of the first PCA3-Gene-ViroTherapy study suggest therapeutic potential by exploiting PCA3 overexpression. Conclusions: PCA3, integrated in novel biopsy nomograms or risk stratification tools, can be used to counsel or confirm biopsy indications. If confirmed in further studies, using PCA3 together with established staging risk factors could assist clinicians in specific pretreatment decision making. So far no evidence for the usefulness of PCA3 in active surveillance programs has been presented. Published by Elsevier B. V. on behalf of European Association of Urology.
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  • Gandaglia, Giorgio, et al. (author)
  • Epidemiology and Prevention of Prostate Cancer
  • 2021
  • In: European Urology Oncology. - : Elsevier. - 2588-9311. ; 4:6, s. 877-892
  • Journal article (peer-reviewed)abstract
    • CONTEXT: Worldwide, prostate cancer (PCa) represents the second most common solid tumor in men.OBJECTIVE: To assess the geographical distribution of PCa, epidemiological differences, and the most relevant risk factors for the disease.EVIDENCE ACQUISITION: Estimated incidence, mortality, and prevalence of PCa for the year 2020 in 185 countries were derived from the IARC GLOBOCAN database. A review of English-language articles published between 2010 and 2020 was conducted using MEDLINE, EMBASE, and Scopus to identify risk factors for PCa.EVIDENCE SYNTHESIS: In the year 2020, there were over 1414000 estimated new cases of PCa worldwide, with an age-standardized rate (ASR) incidence of 31 per 100000 (lifetime cumulative risk: 3.9%). Northern Europe has the highest all-age incidence ASR (83), while the lowest ASR was in South-Central Asia (6.3). In the year 2020, there were over 375000 estimated deaths worldwide, and the overall mortality ASR was 7.7 per 100000, with the highest ASR in the Caribbean (28) and the lowest in South-Central Asia (3.1). Family history, hereditary syndromes, and race are the strongest risk factors for PCa. Metabolic syndrome was associated with the risk of developing PCa, high-grade disease, and adverse pathology. Diabetes and exposure to ultraviolet rays were found to be inversely associated to PCa incidence. Cigarette smoking and obesity may increase PCa-specific mortality, while regular physical activity may reduce disease progression. Although 5-alpha reductase inhibitors are known to be associated with a reduced incidence of PCa, available studies failed to show an effect on overall mortality.CONCLUSIONS: Family history, race, and hereditary syndromes are well-established risk factors for PCa. Modifiable risk factors may impact the risk of developing PCa and that of dying from the disease, but little evidence exist for any clear indication for prevention other than early diagnosis to reduce PCa mortality.PATIENT SUMMARY: Prostate cancer (PCa) rates vary profoundly worldwide, with incidence and mortality rates being highest in Northern Europe and Caribbean, respectively. South-Central Asia has the lowest epidemiological burden. Family history, race, and hereditary syndromes are well-established risk factors for PCa. Modifiable risk factors may impact the risk of developing PCa and that of dying from the disease itself, but little evidence exist for any clear indication for prevention other than early diagnosis to reduce PCa mortality.
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  • Ploussard, Guillaume, et al. (author)
  • The Contemporary Concept of Significant Versus Insignificant Prostate Cancer
  • 2011
  • In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 60:2, s. 291-303
  • Research review (peer-reviewed)abstract
    • Context: The notion of insignificant prostate cancer (Ins-PCa) has progressively emerged in the past two decades. The clinical relevance of such a definition was based on the fact that low-grade, small-volume, and organ-confined prostate cancer (PCa) may be indolent and unlikely to progress to biologic significance in the absence of treatment. Objective: To review the definition of Ins-PCa, its incidence, and the clinical impact of Ins-PCa on the contemporary management of PCa. Evidence acquisition: A review of the literature was performed using the Medline, Scopus, and Web of Science databases with no restriction on language up to September 2010. The literature search used the following terms: insignificant, indolent, minute, microfocal, minimal, low volume, low risk, and prostate cancer. Evidence synthesis: The most commonly used criteria to define Ins-PCa are based on the pathologic assessment of the radical prostatectomy specimen: (1) Gleason score <= 6 without Gleason pattern 4 or 5, (2) organ-confined disease, and (3) tumour volume < 0.5 cm(3). Several preoperative criteria and prognostication tools for predicting Ins-PCa have been suggested. Nomograms are best placed to estimate the risk of progression on an individualised basis, but a substantial proportion of men with a high probability of harbouring Ins-PCa are at risk for pathologic understaging and/or undergrading. Thus, there is an ongoing need for identifying novel and more accurate predictors of Ins-PCa to improve the distinction between insignificant versus significant disease and thus to promote the adequate management of PCa patients at low risk for progression. Conclusions: The exciting challenge of obtaining the pretreatment diagnostic tools that can really distinguish insignificant from significant PCa should be one of the main objectives of urologists in the following years to decrease the risk of overtreatment of Ins-PCa. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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