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Relapse after radical prostatectomy correlates with preoperative PSA velocity and tumor volume: results from a screening population.

OBJECTIVES: To evaluate, in a screening population, the impact of tumor volume and prostate volume on prostate-specific antigen (PSA) velocity (PSAV) and to find predictors of biochemical failure after radical prostatectomy. Longitudinal PSA changes in men with prostate cancer have been reported to be significantly different from those without prostate cancer. METHODS: PSAV was assessed in 102 men undergoing radical retropubic prostatectomy. The pathologic findings of specimens obtained at radical retropubic prostatectomy and pelvic lymph node dissection were analyzed separately for all patients. RESULTS: The median preoperative PSA in the 102 patients was 6.4 ng/mL, the median prostate volume was 32.8 cm3, and the median tumor volume was 1.27 cm3. The PSAV correlated significantly with tumor volume (P <0.05) but not with prostate volume (P = 0.142). The median tumor volume in men with biochemical progression after radical retropubic prostatectomy was 2.55 cm3 versus 0.94 cm3 in men who were free of disease 5 years after surgery. The median PSAV in the year before diagnosis in men with relapse after radical prostatectomy was 1.98 ng/mL/yr versus 1.05 ng/mL/yr in men who had no evidence of disease. CONCLUSIONS: The results of our study have shown that the main factor contributing to the PSAV in patients with prostate cancer is cancer load and that prostate volume is not significantly associated with the PSAV. Men with a PSAV of more than 2 ng/mL/yr in the year before cancer diagnosis are at a high risk of relapse. The PSAV may be helpful in identifying patients with small tumors and thus increase the detection rate of potentially curable prostate cancers.

Adult↗

Basic issues in population screening for cancer.

The value of population screening as an approach to cancer control is controversial because the objectives, benefits, costs, and potential adverse effects of screening programs are not widely agreed upon, nor are the many difficulties involved in evaluating a cancer screening program well recognized. A review of the issues pertinent to cancer screening and their interrelationships is presented. The characteristics of a particular cancer that should be considered before it becomes the target of a screening program are described; emphasis is placed on the prevalence of the detectable preclinical phase. The features of a good screening test are reviewed and the importance of specificity is indicated. Methods for evaluation of screening programs are considered, and the need for measurement of the effects of screening on the mortality rate is emphasized. The biases inherent in some commonly used evaluation procedures, especially lead time bias and length bias, are discussed. The possible adverse effects of cancer screening are pointed out, especially its capacity to increase morbidity. Several approaches to improving cancer screening programs are presented. Finally, the relevance of knowledge regarding the optimum interscreening interval to cancer control and to research issues is described.

Age Factors↗

Population screening for HFE-associated haemochromatosis: should we have to pay for our genes?

Haemochromatosis associated with mutations in the HFE gene is the most common inherited disorder in Caucasian populations. Early diagnosis and treatment allows for normal life expectancy, whereas there is considerable morbidity and early mortality in those patients diagnosed late or untreated. Unfortunately, the development of symptoms and signs in haemochromatosis is usually associated with significant iron overload. For this reason, many clinicians and geneticists have advocated population screening. The recent identification of the HFE gene and the availability of a simple DNA-based diagnostic test have led to international debate as to the most cost-effective means of population screening for HFE-associated haemochromatosis. The present paper summarizes the evidence in favour of population screening and analyses the relative advantages of genotypic (DNA test) versus phenotypic (transferrin saturation) testing.

Cost-Benefit Analysis↗

Extracolonic findings at CT colonography: evaluation of prevalence and cost in a screening population.

BACKGROUND & AIMS: To assess the prevalence and spectrum of extracolonic findings in a screening population undergoing computed tomography colonography (CTC), and to evaluate the short-term direct medical costs incurred from subsequent radiologic follow-up evaluation. METHODS: Six hundred and eighty-one asymptomatic patients undergoing colonoscopy screening consented to a CTC examination. Extracolonic CT findings were classified into high, medium, and low importance. Clinical and radiologic follow-up, missed lesions, and outcomes were assessed by chart review (time interval, 410-1513 days; median, 913 days). Short-term direct medical costs of radiologic follow-up were determined based on Medicare 2002 reimbursement rates. RESULTS: Extracolonic findings were found commonly. These were categorized as high clinical importance in 71 (10%) individuals, as medium importance in 183 individuals (27%), and as low importance in 341 individuals (50%). Subsequent medical or surgical interventions resulted from these findings in 9 of the 681 patients (1.3%). Costs of subsequent radiologic follow-up studies were calculated as $23,380.59 (average added costs per CTC examination $34.33). CONCLUSIONS: CTC commonly detects extracolonic findings that can be considered clinically important when applied to an asymptomatic screening population. Although such incidental findings add benefit to the screening intervention, moderate incremental costs are incurred based on additional radiologic procedures generated during short-term follow-up.

Adult↗

Report on the Dutch consensus development meeting for implementation and further development of population screening for colorectal cancer based on FOBT.

A consensus development meeting was held to evaluate whether or not in the Netherlands all requirements were fulfilled for implementation of population screening with FOBT for colorectal cancer, or whether consensus was present that fulfilment by additional research or organisational actions could be obtained within 2-3 years. There was consensus that all classical Wilson and Jungner (1968) criteria, and six additional ones added more recently, had already been fulfilled or could be fulfilled within 2-3 years. Consequently, it was concluded that a national population screening for colorectal cancer should be implemented and carried out in the Netherlands in line with current national and European cancer screening programmes. A list of organisational actions to be taken was established. Research that is needed before the actual national launch of the screening within 2-3 years has been defined. Priorities have to be set for research and organisational actions for the coming 2-3 years for the implementation of population screening. In addition, research suggestions have been defined for the next 10-15 years for evaluation and/or improvement of implemented FOBT screening, and for future screening methodology. It was considered essential that infrastructure for future research would be embedded in the screening programme. A project group to arrange this should be formed.

Adenoma↗

Perceived risk for Type 2 diabetes in participants in a stepwise population-screening programme.

AIMS: To determine the risk perception of Type 2 diabetes in participants in a stepwise population-screening programme. METHODS: This study was carried out within the framework of a stepwise Type 2 diabetes population screening in the general (age 50-75 years) Dutch population. Main outcome measures were perceived risk of having diabetes and perceived seriousness of diabetes, based on a self-report questionnaire, completed before being informed about the diagnosis (Type 2 diabetes yes/no) of the screening procedure. Among 7736 participants, the risk perception of 217 screening-detected participants was compared with 4435 with a low-risk profile for undiagnosed Type 2 diabetes. RESULTS: Of 7736 participants, 43.5% could not give an estimate of their risk of having diabetes, 31.2% estimated their risk to be 0% and 25.3% estimated their risk to be 10% or higher. Compared with 4435 participants with an objectively low risk profile, 217 screening-detected participants were more likely to answer 'I do not know' (52.4% vs. 40.1%, P < 0.001), perceived their risk less often to be 0% (19.3% vs. 34.7%, P < 0.001), and slightly more often perceived their risk to be 10% or higher (28.3% vs. 25.2%, P < 0.001). Overall, more than half of the total population, including both participants with a low risk profile and the screening-detected participants, perceived diabetes as a (very) serious disease. Higher age, obesity and taking anti-hypertensive drugs did not translate into a higher perceived risk. CONCLUSIONS: Among screening-detected participants the seriousness of Type 2 diabetes was generally acknowledged, whilst the perceived risk of having Type 2 diabetes was low, despite the presence of risk factors.

Aged↗

Economic evaluation of prenatal population screening for fragile X syndrome.

OBJECTIVES: This paper models costs and benefits of a population screening programme for pregnant women to detect fragile X syndrome. Given the high lifetime costs of fragile X and the high sensitivity and specificity of testing, such a programme may seem attractive. METHODS: Economic evaluation. RESULTS: Our base case results indicate that such a programme seems close to cost neutral, so may indeed seem attractive for this reason. However, sensitivity analysis shows that assumptions regarding lifetime costs are crucial to results; our results suggest if lifetime costs are under AUD 2.5 million, costs of screening will exceed future costs avoided. CONCLUSIONS: Economic modelling of screening programmes reveals valuable information which might have an influence on the debate on the social value of a population screening programme for fragile X in pregnant women.

Australia↗

Effect of population screening for cancer of the uterine cervix in Nijmegen, The Netherlands.

Since the introduction of a population screening program for cervical cancer in 1976, more than 85% of the female population between the ages of 35 and 54 years in the region of the city of Nijmegen, The Netherlands, has been screened. At first screening, severe epithelial abnormalities were diagnosed in 4.4 per 1,000 women, at second screening, in 1.5 per 1,000; and at third screening, in 1.0 per 1,000. The population screening program led to a marked increase in the detected number of carcinomata in situ. The number of cases of squamous cell cancer diagnosed in the first screening period did not increase. Once the population was screened, the detection rate of invasive squamous cell cancer in the group of women ages 35 through 54 decreased from 18.6 per 10(5) during the period prior to the screening to 9.0 per 10(5) after the first screening and 3.3 per 10(5) after the second screening. For the women above age 54, the incidence of invasive cancer was reduced by 58% after the second screening. The number of invasive cancers diagnosed in women under age 35 remained relatively small in spite of the large number of cases of carcinoma in situ.

Adult↗

A randomised trial of population screening for melanoma.

OBJECTIVES: Melanoma is a significant cause of morbidity and mortality worldwide and incidence is increasing. Survival after treatment is inversely related to the thickness of the tumour at diagnosis. Population screening has the potential to reduce mortality but there is no conclusive evidence of benefit. Such evidence can come best from a randomised trial. Here we describe the design of a community based randomised trial of a population screening programme for melanoma in Queensland, Australia and early results of the first phase of the trial. METHODS: A total of 44 communities (aggregate population 560 000 adults aged 30 years or more) will be randomised to receive either a community based screening programme for 3 years or normal practice. The screening programme promotes thorough skin self examination and whole body skin examination by a doctor and provides open access skin cancer screening clinics. In its first phase, the trial is underway in nine intervention and nine control communities. The primary outcome measure is mortality from melanoma during 15 years of follow up. RESULTS: The first phase of the trial has shown the feasibility of implementing a population skin screening programme including regular skin cancer screening clinics, and has shown the strong support of communities and doctors for the programme. There has been a significant 2.5-fold increase in participation in screening in the intervention communities in this first phase after the first 12 months of the trial and no significant increase in participation in screening in control communities during this period. CONCLUSIONS: The design of a community based randomised trial of screening for melanoma has been successfully peer reviewed and the intervention has been shown to be feasible in practice. This randomised trial may be one of the last opportunities to develop the evidence required for public health recommendations for population screening for melanoma.

Humans↗

[Test for human papillomavirus: no added value by inclusion in improved population screening for cervical cancer at this point].

There is convincing evidence that high risk types of human papilloma virus (hrHPV) infection are strongly associated with the development of (the majority of) cervical carcinomas. The tumour-biological model will undoubtedly provide several potential cellular progression markers in the near future. As it is, there is not sufficient evidence to include the detection of hrHPV in the Dutch population screening programme. The population screening programme has in the recent years been reorganized, with many favourable effects in effectiveness and efficiency. It is proposed to start research projects at the regional level of the screening programme to test the applicability of newly developed molecular markers.

Adult↗

Comparison of genotypic and phenotypic strategies for population screening in hemochromatosis: assessment of anxiety, depression, and perception of health.

PURPOSE: Hemochromatosis is a treatable disorder with a major genetic predisposition. It provides an example in which genotypic and phenotypic strategies for screening may be compared. We previously showed noninferiority of uptake of a genotypic population screening strategy for hemochromatosis compared with a phenotypic strategy. In this article we present the psychologic effects of each strategy. METHODS: A sample of 3000 individuals from primary care were randomly allocated to a phenotypic or genotypic screening strategy for hemochromatosis, and the 939 individuals who accepted screening provide the sample for this article. Standardized assessments of anxiety, general health, and depression were made at invitation, testing, result-giving, and 6 months. RESULTS: Screening did not lead to significant changes in the self-rated assessments of anxiety, depression, and general health over time, and there were no significant differences between the two screening strategies. The unemployed or permanently disabled had lower ratings of health and higher anxiety and depression. CONCLUSION: The two screening strategies appeared to cause little adverse psychologic disturbance in the short term, and there was no difference between the two strategies This study provides some empiric data to support arguments against "genetic exceptionalism" and suggests that genetic testing when used for population screening for a treatable disease has few adverse effects.

Adult↗

Acceptability of voluntary population screening for antibodies against HIV. Aarhus Research Group on AIDS.

In order to assess the acceptability of voluntary population screening for antibodies against human immunodeficiency virus (HIV), a random sample of 300 Danish men, aged 20-49 years, were sent a self-administered questionnaire. Among nonrespondents, recruitment attempts were repeated three times with intervals of 8-10 days. In total, 76.7% responded. Two hundred men (87.0% of the respondents) would accept an offer to be tested in an anti-HIV screening programme. Among respondents, 72.9% agreed to identify themselves to the researchers, 22.1% preferred to be tested under a code number known only by the participant himself, and 5% wanted the test information to be completely anonymous. Among the 30 men refusing HIV testing, 40% reported they were not concerned about AIDS, 16.7% expressed concern with confidentiality problems, and another 16.7% had been tested already and for this reason declined to participate. Previous reports have indicated high seroprevalences among nonrespondents and raised prevalences of behavior at high risk for HIV infection among persons who do themselves take the initiative to be tested or who decline to be tested because they worry about confidentiality. Low respondency and the associated disproportional loss of subjects at high risk of HIV infection may bias HIV seroprevalence estimates based on population probability sampling, especially in areas with low HIV infection prevalence. Because of these biases, voluntary population screening is likely to give only lower bound estimates of HIV seroprevalence. So, this technique should only be used in combination with other surveillance approaches.

Adult↗

[Differential diagnosis of arterial hypertension at a city polyclinic with mass population screening].

The paper discusses the problems of differential diagnosis between varying types of arterial hypertension detected during mass screening of the population. Randomized examination was made in 45% of male population aged 40-59 years. Arterial hypertension was observed in 26.3% of the examinee; 24.5% showed a rise in the arterial pressure for the first time. The methods of investigation available at the city polyclinic allowed the authors to diagnose hypertension in 85.2% of the patients. The results of isotope renography included into the complex of the study enabled them to determine the indications for the method to be used in mass screening of the population for revealing arterial hypertension.

Adult↗

Effectiveness of glycosylated hemoglobin, fasting plasma glucose, and a single post load plasma glucose level in population screening for glucose intolerance.

Five shortcut methods of population screening for glucose intolerance (impaired glucose tolerance and non-insulin-dependent diabetes mellitus) were assessed for effectiveness: 1) glycosylated hemoglobin concentration (HbA1), 2) fasting plasma glucose level, 3) combinations of fasting plasma glucose and HbA1, 4) plasma glucose one hour post oral glucose load, and 5) plasma glucose two hour post oral glucose load. In a sample of the Israeli Jewish population aged 40-70 years, 2040 participants in the Israel Study of Glucose Intolerance, Obesity and Hypertension, who were not known to be diabetic, underwent an oral glucose tolerance test based on three blood samples (fasting, one hour, and two hour post oral glucose load). In 1058 of the subjects, HbA1 was also measured, and was found to increase significantly (P less than 0.001) with increasing glucose intolerance, but with extensive overlap of ranges, even between normals and newly found diabetics. Fasting plasma glucose was more effective than HbA1 in screening for both impaired glucose tolerance and diabetes by its higher specificity and predictive value of a positive test at comparable sensitivity levels. Combinations of HbA1 and fasting plasma glucose did not improve prediction over fasting plasma glucose alone. As observed in other studies, the screening effectiveness of fasting plasma glucose was also unsatisfactory, either post load glucose level being more effective. Plasma glucose level two hour post load was better for detection of diabetes alone. Plasma glucose level one hour post load was more effective at detecting the total group of glucose intolerance, but did not discriminate well between impaired tolerance and diabetes. A cost-risk-benefit evaluation suggests that a full three-sample oral glucose tolerance test is the best method in screening for both intolerance categories.

Adult↗

Population screening for hemochromatosis--are we finding people with a disease or a biochemical curiosity?

Hemochromatosis is a common genetic disease in which early diagnosis and treatment results in an excellent long-term prognosis. Population screening projects have been completed that included iron tests and genetic testing. In this review, the controversial issues surrounding population screening for hemochromatosis are explored in the context of available information from large screening studies.

Genetic Counseling↗

Cost-effectiveness of population screening for Helicobacter pylori in preventing gastric cancer and peptic ulcer disease, using simulation.

OBJECTIVES: To evaluate the cost-effectiveness of population screening for Helicobacter pylori in preventing gastric cancer and peptic ulcer disease in England and Wales. METHODS: A discrete event simulation model used parameter estimates, derived from peer-reviewed literature, routine data and statistical modelling. Population screening was compared with no screening but with opportunistic eradication in patients presenting with dyspepsia. Costs included screening, eradication and costs averted to provide costs per life years saved (cost/LYS) for preventing gastric cancer and peptic ulcer disease. Sensitivity analyses were undertaken. RESULTS: The cost/LYS from screening at age 40 years was Uk pounds 5860 at discount rates of 6%. The outcomes were sensitive to H. pylori prevalence, the degree of opportunistic eradication, the discount rate, the efficacy of eradication on gastric cancer risk, the risk of complicated peptic ulcer disease and gastric cancer associated with H. pylori infection, and the duration of follow-up. In sensitivity analyses, the cost/LYS rarely exceeded UK pounds 20000 over an 80-year follow-up, but did for shorter periods. CONCLUSIONS: H. pylori screening may be cost-effective in the long term. However, before screening can be recommended further evidence is needed to resolve some of the uncertainties, particularly over the efficacy of eradication on risk of gastric cancer, the risk associated with complicated peptic ulcers, and the effect of more widespread opportunistic testing of patients with dyspepsia.

Adult↗

The effect of percentage free prostate-specific antigen (PSA) level on the prostate cancer detection rate in a screening population with low PSA levels.

OBJECTIVE: To evaluate the prostate cancer detection rate at low total prostate-specific antigen (tPSA) ranges of 2.6-4 and 4.1-10 ng/mL, according to different percentage free (f/t) PSA levels in a screening population. SUBJECTS AND METHODS: In all, 1809 consecutive screening volunteers with a tPSA level of 2.6-10.0 ng/mL were assessed. Ten systematic ultrasonography-guided prostate biopsies and, since 2000, an additional five Doppler-enhanced targeted biopsies were taken on the basis of age-specific tPSA reference ranges. We analysed the detection rate of prostate cancer according to f/tPSA ranges of 0-9%, 10-14%, 15-18% and >18%. RESULTS: The detection rates for the subgroups with tPSA levels of 2.6-4.0 and 4.1-10.0 ng/mL were 20.2% and 27.0%, respectively. The cancer detection rate in the first group (2.6-4.0 ng/mL) at 0-10% fPSA was 22.9%, and that in the second group (4.1-10.0 ng/mL) at 0-10% was 36.9%. There were significant differences between these groups. If the f/tPSA was 10-15%, the cancer detection rate for the two groups were 22.6% and 32.5%, respectively (P < 0.05). There was no statistically significant difference in the cancer detecting rates at an f/tPSA of 15-18% or >18%. CONCLUSION: There is a statistically significantly higher cancer detection rate when the f/tPSA is <15% than in groups of men with a f/tPSA of >15% in screening population assessed primarily using tPSA level.

Adult↗

Surgical implications of population screening for mammary carcinoma.

With the introduction of population screening for mammary carcinoma, in the initial phase an increase of malignancies has to be expected. Later on in the program the type of lesions will change. In the case of nonpalpable lesions close cooperation between surgeon, radiologist and pathologist is mandatory. The treatment of patients with ductal carcinoma in situ needs special attention because of the complexity of the problem, and requires careful preparation of the disciplines involved.

Aged↗