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      The feasibility and results of a population-based approach to evaluating prostate-specific antigen screening for prostate cancer in men with a raised familial risk

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          Abstract

          The feasibility of a population-based evaluation of screening for prostate cancer in men with a raised familial risk was investigated by studying reasons for non-participation and uptake rates according to postal recruitment and clinic contact. The levels of prostate-specific antigen (PSA) and the positive predictive values (PPV) for cancer in men referred with a raised PSA and in those biopsied were analysed. First-degree male relatives (FDRs) were identified through index cases (ICs): patients living in two regions of England and diagnosed with prostate cancer at age ⩽65 years from 1998 to 2004. First-degree relatives were eligible if they were aged 45–69 years, living in the UK and had no prior diagnosis of prostate cancer. Postal recruitment was low (45 of 1687 ICs agreed to their FDR being contacted: 2.7%) but this was partly due to ICs not having eligible FDRs. A third of ICs in clinic had eligible FDRs and 49% (192 out of 389) agreed to their FDR(s) being contacted. Of 220 eligible FDRs who initially consented, 170 (77.3%) had a new PSA test taken and 32 (14.5%) provided a previous PSA result. Among the 170 PSA tests, 10% (17) were ⩾4 ng ml −1 and 13.5% (23) tests above the age-related cutoffs. In 21 men referred, five were diagnosed with prostate cancer (PPV 24%; 95% CI 8, 47). To study further the effects of screening, patients with a raised familial risk should be counselled in clinic about screening of relatives and data routinely recorded so that the effects of screening on high-risk groups can be studied.

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          Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

          The objectives of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55-74 at entry whether screening with flexible sigmoidoscopy (60-cm sigmoidoscope) can reduce mortality from colorectal cancer, whether screening with chest X-ray can reduce mortality from lung cancer, whether screening men with digital rectal examination (DRE) plus serum prostate-specific antigen (PSA) can reduce mortality from prostate cancer, and whether screening women with CA125 and transvaginal ultrasound (TVU) can reduce mortality from ovarian cancer. Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity, specificity, and positive predictive value; to assess incidence, stage, and survival of cancer cases; and to investigate biologic and/or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints. The design is a multicenter, two-armed, randomized trial with 37,000 females and 37,000 males in each of the two arms. In the intervention arm, the PSA and CA125 tests are performed at entry, then annually for 5 years. The DRE, TVU, and chest X-ray exams are performed at entry and then annually for 3 years. Sigmoidoscopy is performed at entry and then at the 5-year point. Participants in the control arm follow their usual medical care practices. Participants will be followed for at least 13 years from randomization to ascertain all cancers of the prostate, lung, colorectum, and ovary, as well as deaths from all causes. A pilot phase was undertaken to assess the randomization, screening, and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels. This paper describes eligibility, consent, and other design features of the trial, randomization and screening procedures, and an outline of the follow-up procedures. Sample-size calculations are reported, and a data analysis plan is presented.
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            International trends and patterns of prostate cancer incidence and mortality.

            Prostate cancer is the most commonly diagnosed cancer in western men, and incidence is rising rapidly in most countries, including low-risk populations. Age-adjusted incidence and mortality rates from 15 and 13 countries between 1973-77 and 1988-92, respectively, were compared to provide leads for future analytic studies. Large increases in both incidence and mortality rates of prostate cancer were seen for all countries. For incidence, increases were more pronounced in the United States, Canada, Australia, France and the Asian countries, while the increases in medium-risk countries were moderate. Increases in incidence ranged from 25%-114%, 24%-55% and 15%-104% in high-, medium- and low-risk countries, respectively. Mortality rates rose more rapidly in Asian countries than in high-risk countries. Substantial differences in incidence and mortality across countries were evident, with U.S. blacks having rates that were 50-60 times higher than the rates in Shanghai, China. Increasing incidence rates in the United States and Canada are likely to be due in part to the widespread use of transurethral resection of the prostate and prostate-specific antigen testing, while increases in the Asian countries are probably related to westernization in these low-risk populations. The large disparities in incidence between high- and low-risk countries may be due to a combination of genetic and environmental factors. Future studies are needed to examine gene-gene and gene-environment interactions in various countries concurrently to shed light on the etiology of prostate cancer and to help elucidate reasons for the large differences in risk between populations. Copyright 2000 Wiley-Liss, Inc.
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              Sociodemographic factors and delays in the diagnosis of six cancers: analysis of data from the ‘National Survey of NHS Patients: Cancer'

              This paper aims to explore the relationship between sociodemographic factors and the components of diagnostic delay (total, patient and primary care, referral, secondary care) for these six cancers (breast, colorectal, lung, ovarian, prostate, or non-Hodgkin's lymphoma). Secondary analysis of patient-reported data from the ‘National Survey of NHS patients: Cancer' was undertaken (65 192 patients). Data were analysed using univariate analysis and Generalised Linear Modelling. With regard to total delay, the findings from the GLM showed that for colorectal cancer, the significant factors were marital status and age, for lung and ovarian cancer none of the factors were significant, for prostate cancer the only significant factor was social class, for non-Hodgkin's lymphoma the only significant factor was age, and for breast cancer the significant factors were marital status and ethnic group. Where associations between any of the component delays were found, the direction of the association was always in the same direction (female subjects had longer delays than male subjects, younger people had longer delays than older people, single and separated/divorced people had longer delays than married people, lower social class groups had longer delays than higher social class groups, and Black and south Asian people had longer delays than white people). These findings should influence the design of interventions aimed at reducing diagnostic delays with the aim of improving morbidity, mortality, and psychological outcomes through earlier stage diagnosis.
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                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                24 January 2006
                21 February 2006
                27 February 2006
                : 94
                : 4
                : 499-506
                Affiliations
                [1 ]Cancer Screening Evaluation Unit, Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
                [2 ]Academic Unit of Radiotherapy & Oncology, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK
                [3 ]Psychology Research Group, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK
                [4 ]University College Hospitals and Institute of Urology, UCL, London SW1 V3JN, UK
                [5 ]Translational Cancer Genetics Team, Institute of Cancer Research & Cancer Genetics Unit, Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK
                [6 ]Psychological Medicine, Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK
                Author notes
                [* ]Author for correspondence: jane.melia@ 123456icr.ac.uk
                Article
                6602925
                10.1038/sj.bjc.6602925
                2361168
                16434997
                9bcfed67-76b5-4d7e-a894-f18dcb16321d
                Copyright 2006, Cancer Research UK
                History
                : 19 October 2005
                : 30 November 2005
                Categories
                Clinical Studies

                Oncology & Radiotherapy
                prostatic neoplasm,mass screening,family health,prostate-specific antigen

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