Effectiveness Of Prostate Cancer Screening Research Articles

Early detection of clinically significant prostate cancer: protocol summary and statistical analysis plan for the ProScreen randomised trial

IntroductionEvidence on the effectiveness of prostate cancer screening based on prostate-specific antigen is inconclusive and suggests a questionable balance between benefits and harms due to overdiagnosis, and complications from biopsies...

EPH132 Effectiveness of Prostate Cancer Screening in Reducing Adult Mortality: A Quasi-Systematic Review

Prostate cancer (PCa) is the most frequently-diagnosed male cancer and the leading cause of cancer death in developed countries. Observed reduction in PCa-mortality rates have been linked to earlier diagnosis due to screening access and treatment improvements. This review aimed to investigate the effectiveness of PCa screening in reducing mortality rates among adults.

Interpreting cost-effectiveness ratios in a cost-effectiveness analysis of risk-tailored prostate screening: A critique of Callender et al.

Callender et al. recently published a model-based cost-effectiveness analysis of a risk-tailored approach to prostate cancer screening. It considers the costs and effects of prostate cancer screening offered to all men aged 55-69 without any risk selection and, alternatively, over a range of risk-tailored strategies in which screen eligibility is determined by a varying threshold of disease risk. The analysis finds that the strategy of screening men once they reach a 10-year absolute risk of disease of 5% or more is cost-effective in a UK context. I believe there are several problems with the study, mostly stemming from an incorrect interpretation of the cost-effectiveness estimates. I show that one reinterpretation of their results indicates that screening is much less cost-effective than the original analysis suggests, indicating that screening should be restricted to a much smaller group of higher risk men. More broadly, I explain the challenges of attempting to meaningfully reinterpret the originally published results due to the simulation of non-mutually exclusive intervention strategies. Finally, I consider the relevance of considering sufficient alternative screening intensities. This critique highlights the need for appropriate interpretation of cost-effectiveness results for policymakers, especially as risk stratification within screening becomes increasingly feasible.

Interpreting cost-effectiveness ratios in a cost-effectiveness analysis of risk-tailored prostate screening: A critique of Callender et al.

Callender et al. recently published a model-based cost-effectiveness analysis of a risk-tailored approach to prostate cancer screening. It considers the costs and effects of prostate cancer screening offered to all men aged 55-69 without any risk selection and, alternatively, over a range of risk-tailored strategies in which screen eligibility is determined by a varying threshold of disease risk. The analysis finds that the strategy of screening men once they reach a 10-year absolute risk of disease of 5% or more is cost-effective in a UK context. I believe there are several problems with the study, mostly stemming from an incorrect interpretation of the cost-effectiveness estimates. I show that one reinterpretation of their results indicates that screening is much less cost-effective than the original analysis suggests, indicating that screening should be restricted to a much smaller group of higher risk men. More broadly, I explain the challenges of attempting to meaningfully reinterpret the originally published results due to the simulation of non-mutually exclusive intervention strategies. Finally, I consider the relevance of considering sufficient alternative screening intensities. This critique highlights the need for appropriate interpretation of cost-effectiveness results for policymakers, especially as risk stratification within screening becomes increasingly feasible.

A Cost-Utility Analysis of Prostate Cancer Screening in Australia.

The Göteborg randomised population-based prostate cancer screening trial demonstrated that prostate-specific antigen (PSA)-based screening reduces prostate cancer deaths compared with an age-matched control group. Utilising the prostate cancer detection rates from this study, we investigated the clinical and cost effectiveness of a similar PSA-based screening strategy for an Australian population of men aged 50-69 years. A decision model that incorporated Markov processes was developed from a health system perspective. The base-case scenario compared a population-based screening programme with current opportunistic screening practices. Costs, utility values, treatment patterns and background mortality rates were derived from Australian data. All costs were adjusted to reflect July 2015 Australian dollars (A$). An alternative scenario compared systematic with opportunistic screening but with optimisation of active surveillance (AS) uptake in both groups. A discount rate of 5% for costs and benefits was utilised. Univariate and probabilistic sensitivity analyses were performed to assess the effect of variable uncertainty on model outcomes. Our model very closely replicated the number of deaths from both prostate cancer and background mortality in the Göteborg study. The incremental cost per quality-adjusted life-year (QALY) for PSA screening was A$147,528. However, for years of life gained (LYGs), PSA-based screening (A$45,890/LYG) appeared more favourable. Our alternative scenario with optimised AS improved cost utility to A$45,881/QALY, with screening becoming cost effective at a 92% AS uptake rate. Both modelled scenarios were most sensitive to the utility of patients before and after intervention, and the discount rate used. PSA-based screening is not cost effective compared with Australia's assumed willingness-to-pay threshold of A$50,000/QALY. It appears more cost effective if LYGs are used as the relevant outcome, and is more cost effective than the established Australian breast cancer screening programme on this basis. Optimised utilisation of AS increases the cost effectiveness of prostate cancer screening dramatically.

Correction: Absolute Effect of Prostate Cancer Screening: Balance of Benefits and Harms by Center within the European Randomized Study of Prostate Cancer Screening.

Correction: Absolute Effect of Prostate Cancer Screening: Balance of Benefits and Harms by Center within the European Randomized Study of Prostate Cancer Screening.

Absolute Effect of Prostate Cancer Screening: Balance of Benefits and Harms by Center within the European Randomized Study of Prostate Cancer Screening.

The balance of benefits and harms in prostate cancer screening has not been sufficiently characterized. We related indicators of mortality reduction and overdetection by center within the European Randomized Study of Prostate Cancer Screening (ERSPC). We analyzed the absolute mortality reduction expressed as number needed to invite (NNI = 1/absolute risk reduction; indicating how many men had to be randomized to screening arm to avert a prostate cancer death) for screening and the absolute excess of prostate cancer detection as number needed for overdetection (NNO = 1/absolute excess incidence; indicating the number of men invited per additional prostate cancer case), and compared their relationship across the seven ERSPC centers. Both absolute mortality reduction (NNI) and absolute overdetection (NNO) varied widely between the centers: NNI, 200-7,000 and NNO, 16-69. Extent of overdiagnosis and mortality reduction was closely associated [correlation coefficient, r = 0.76; weighted linear regression coefficient, β = 33; 95% confidence interval (CI), 5-62; R(2) = 0.72]. For an averted prostate cancer death at 13 years of follow-up, 12 to 36 excess cases had to be detected in various centers. The differences between the ERSPC centers likely reflect variations in prostate cancer incidence and mortality, as well as in screening protocol and performance. The strong interrelation between the benefits and harms suggests that efforts to maximize the mortality effect are bound to increase overdiagnosis and might be improved by focusing on high-risk populations. The optimal balance between screening intensity and risk of overdiagnosis remains unclear.

Rastreio do cancro prostático: o actual paradigma da medicina centrada na pessoa

For several years, there has been debate regarding the cost effectiveness of prostate cancer screening. In 2012 the U.S. Preventive Services Task Force (USPSTF) recommended against screening for prostate cancer, concluding that there is considerable evidence that this is not beneficial. The impact of the recommendations of USPSTF may be noted in the guidelines produced by other scientific societies. Clinicians need to know the evidence. The results of two randomized controlled trials, the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) and the European Randomized Study of Screening for Prostate Cancer (ERSPC), form the largest body of current evidence, although both have limitations. An analysis of the results of these trials shows a small reduction in prostate cancer deaths among men who were screened. The first trial showed no reduction in mortality [RR = 1.09 (0.87 to 1.36)], while the latter trial showed that the number of deaths from prostate cancer was 5 per 1000 men in the group without screening and 4 per 1000 men undergoing screening [RR = 0.79 (0.68 to 0.91)] after 11 years of follow up. There is evidence that 100 to 200 men per 1000 men screened will have a false-positive test. Most of these men will undergo prostate biopsy. A large proportion of patients with prostatic carcinomas detected by screening may be subjected to surgery, radiotherapy or androgen deprivation therapy. This article highlights the evidence against systematic screening. It proposes a holistic approach involving the individual in the discussion of the advantages and disadvantages of prostate cancer screening.

Impact of screening and treatment on racial and ethnic differences in health service use, cost, and mortality among advanced (T3 or greater) prostate cancer patients.

131 Background: Limited information is available regarding the association between race/ethnicity, health service use, cost, and mortality in older patients with advanced (T3 or greater) stage prostate cancer. The objective is to analyze the race/ethnic differences in mortality, cost, and assess the mediating effect of prostate cancer screening and treatment on these differences in fee-for-service Medicare patients with advanced prostate cancer Methods: Retrospective, observational, case-control study using SEER-Medicare linked data. Cohort consisted of 15,054 elderly men diagnosed with advanced stage prostate cancer between 2001and 2004 and followed retrospectively for up to 2009. Cancer-free controls from Medicare data were used to determine the incremental cost of advanced stage prostate cancer. Racial/ethnic variation in health service use, cost, and mortality were analyzed using Poisson, GLM log-link, and Cox regression models. Results: For the age 66 to 75 and 76 to 85, age groups, racial/ethnic differences in health service use, cost, and all cause mortality were observed. Blacks were less likely to have received prostate cancer screening in the year prior to diagnosis of advanced prostate cancer, less likely to have received any treatment after diagnosis and had higher disease specific mortality. After adjusting for prostate cancer screening and treatment across age groups however, odds of prostate cancer-specific mortality were comparable between racial/ethnic groups suggesting that screening may have some mitigating effect on outcomes in the AA population HR 1.23 (1.07-1.41) versus HR 1.12(0.98-1.29). Conclusions: The pattern of racial/ethnic disparity varies by age group with higher mortality among black men. This may be attributable to disparity in prostate cancer screening or treatment. This suggests that the lack of consideration for racial considerations in the U.S. Preventive Services Task Force PSA recommendations could have disparate racial impact.

Effects of prostate cancer screening on health-related quality of life: Results of the Finnish arm of the European randomized screening trial (ERSPC)

Background. As prostate cancer (PC) mortality reduction results are not unequivocal, a special emphasis has to be put on other aspects of the prostate-specific antigen (PSA) screening, including effects on quality of life. In the present study we describe the short-term effects of various phases of PC screening on health-related quality of life (HRQL). Material and methods. The study participants were randomized into the screening arm within the Finnish component of the European Randomized Study on Screening for Prostate Cancer (ERSPC). The RAND 36-Item Health Survey on HRQL and questionnaires on sociodemographic and behavioral factors were delivered to participants at various phases of the first screening round: 1) 500 participants at invitation; 2) 500 after screening; 3) 500 after obtaining the PSA result; 4) to 300 participants after undergoing digital rectal examination (DRE) (but prior to being informed of its result); and 5) approximately 300 after prostate biopsy. At each stage, a new sample of participants was recruited. Results. Response rates were 59% at invitation, 77% after PSA blood test, 54% after PSA result and 69% after DRE. The men recruited at each stage were comparable in respect to socioeconomic variables. The HRQL scores in RAND-36 subscales showed little variation in the different phases of the screening process. Compared with the previous phase, the social function score was slightly lower after obtaining the PSA result than after blood test, the emotional role score lower after DRE than after PSA result and the pain-related score lower after DRE than after TRUS and biopsy. The screening participants were comparable to the general population as their HRQL scores were similar to an age-stratified general Finnish male population. Conclusion. Short-term HRQL effects of prostate cancer screening appear minor and transient.

Screening for prostate cancer

Any form of screening aims to reduce mortality and increase a person's quality of life. Screening for prostate cancer has generated considerable debate within the medical community, as demonstrated by the varying recommendations made by medical organizations and governed by national policies. Much of this debate is due to the limited availability of high quality research and the influence of false-positive or false-negative results generated by use of the diagnostic techniques such as the digital rectal examination (DRE) and prostate specific antigen (PSA) blood test.To determine whether screening for prostate cancer reduces prostate cancer mortality and has an impact on quality of life.Electronic databases (PROSTATE register, CENTRAL the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CANCERLIT and the NHS EED) were searched electronically in addition to hand searching of specific journals and bibliographies in an effort to identify both published and unpublished trials.All randomised controlled trials of screening versus no screening or routine care for prostate cancer were eligible for inclusion in this review.The search identified 99 potentially relevant articles that were selected for full text review. From these 99 citations, two randomised controlled trials were identified as meeting the review's inclusion criteria. Data from the trials were independently extracted by two authors.Two randomised controlled trials with a total of 55,512 participants were included; however, both trials had methodological weaknesses. Re-analysis using intention-to-screen and meta-analysis of results from the two randomised controlled trials indicated no statistically significant difference in prostate cancer mortality between men randomised for prostate cancer screening and controls (RR 1.01, 95% CI: 0.80-1.29). Neither study assessed the effect of prostate cancer screening on quality of life, all-cause mortality or cost effectiveness.Given that only two randomised controlled trials were included, and the high risk of bias of both trials, there is insufficient evidence to either support or refute the routine use of mass, selective or opportunistic screening compared to no screening for reducing prostate cancer mortality. Currently, no robust evidence from randomised controlled trials is available regarding the impact of screening on quality of life, harms of screening, or its economic value. Results from two ongoing large scale multicentre randomised controlled trials that will be available in the next several years are required to make evidence-based decisions regarding prostate cancer screening.

Prostate Cancer Treatment on the Basis of an Individual Risk Profile; Can we Reduce Overtreatment?

Prostate cancer (PCa) is the most prevalent cancer in male population with an incidence rate of 93 per 100.000 men in Europe and is the sixth leading cause of cancer related deaths in men. In the last two decades the incidence of PCa has increased, which is related to widespread prostate-specific antigen (PSA) based screening and increased life expectancy. Mortality rates of prostate cancer have been reduced due to improvement in treatment and/or the widespread screening activities. Major down sides of screening are the potential risks of overdiagnosis and subsequent overtreatment. Approximately 50% of PCa cases detected through screening are potentially overdiagnosed and hence do not require active treatment. However, in clinical practice men with a potentially non-life-threatening cancer (indolent cancer) are often treated actively resulting in unnecessary suffering from serious side effects coinciding with active treatment. The way out of this dilemma is two-fold. First, the actual diagnosis could be delayed or even avoided and second, radical treatment could be delayed or avoided for patients with low-risk PCa. To better predict the presence of a (potentially indolent) prostate cancer nomograms have been developed. These multivariate prediction tools can be of aid in avoiding unnecessary biopsies reducing overdiagnosis, or identifying potentially indolent prostate cancer after diagnosis and hence adapt the treatment strategy. In this expert opinion we discuss the available tools and their performance in reducing the unwanted side effects of prostate cancer screening. In addition, we provide an overview of strategies concerning optimisation and individualisation of treatment, to reduce overtreatment of prostate cancer.

How Effective is Population-Based Cancer Screening? Regression Discontinuity Estimates from the U.S. Guideline Screening Initiation Ages

U.S. cancer screening guidelines recommend that cancer screening begin for breast cancer at age 40 and for colorectal cancer and prostate cancers at age 50. What are the marginal returns to physician and individual compliance with these cancer screening guidelines? We estimate the marginal benefits by comparing cancer test and cancer detection rates on either side of recommended initiation ages (age 40 for breast cancer, age 50 for colorectal and prostate cancers). Using a regression discontinuity design and self-reported test data from national health surveys, we find test rates for breast, colorectal, and prostate cancer increase at the guideline age thresholds by 78%, 65% and 4%, respectively. Data from cancer registries in twelve U.S. states indicate that cancer detection rates increase at the same thresholds by 25%, 27% and 17%, respectively. We estimate statistically significant effects of screening on breast cancer detection (1.3 cases/1000 screened) at age 40 and colorectal cancer detection (1.8 cases/1000 individuals screened) at age 50. We do not find a statistically significant effect of prostate cancer screening on prostate cancer detection. Fifty and 65 percent of the increases in breast and colorectal case detection, respectively, occur among middle-stage cancers (localized and regional) with the remainder among early-stage (in-situ). Our analysis suggests that the cost of detecting an asymptomatic case of breast cancer at age 40 is approximately $100,000-125,000 and that the cost of detecting an asymptomatic case of colorectal cancer at age 50 is approximately $306,000-313,000. We also find suggestive evidence of mortality benefits due to the increase in U.S. breast cancer screening at age 40 and colorectal cancer screening at age 50.

Primary care perspectives on Prostate cancer screening

Although the effectiveness of prostate cancer screening is controversial, screening rates have risen dramatically among primary care providers in the United States. The authors' findings suggest more collaboration among primary care and specialty organizations, especially with respect to decision aid endorsement, is needed to achieve more discriminatory and patient-centered prostate cancer screening.

Disease-specific mortality may underestimate the total effect of prostate cancer screening

To study the difference between the disease-specific and excess mortality rate in the European Randomized Study of Screening for Prostate Cancer section Rotterdam. A total of 42,376 men were randomized to systematic screening or usual care. The excess number of deaths was defined as the difference between the observed number of deaths in the prostate cancer (PC) patients and the expected number of deaths up to 31 December 2006. The expected number was derived from mortality of all study participants before a possible diagnosis with PC. The disease-specific mortality rate was based on the number of men who died from PC. The excess mortality rate based on the arm-specific excess number of deaths and the disease-specific mortality rate were compared between the two study arms. The overall mortality rate was not significantly different between the intervention and the control arms of the study: RR 1.02 (95% CI 0.98-1.07). The disease-specific mortality rate was 0.42 men per 1000 person-years in the intervention and 0.48 men per 1000 person-years in the control arm: RR 0.86 (95% CI 0.64-1.17). The excess mortality rate was 0.40 per 1000 person-years in the intervention arm and 0.61 men per 1000 person-years in the control arm, and the RR for excess mortality was 0.66 (95% CI 0.39-1.13). In contrast to the disease-specific mortality rates an increased difference in the excess mortality rates was observed between the two arms. This observation may be due to a systematic underestimation of the disease-specific deaths, and/or an additional disease-related mortality that is measured by an excess mortality analysis but not by a disease-specific mortality.

The effect of prostate cancer screening on stage IV disease in America

Some studies have found that prostate cancer (PCa) screening provides little or no change in PCa-related mortality during the 7-10 years following diagnoses. However, most men are diagnosed with PCa at low-stage disease and die of unrelated causes during this period. Men diagnosed at stage IV are at much higher risk of dying of the disease. Therefore, stage IV rates at first diagnoses may be a surrogate marker of PCa-related mortality over a time span less than 10 years. The study objective is to examine the association between PCa screening and stage IV disease rates in new cases to explore potential benefits for PCa screening. The percent of stages I, II, III, IV and unclassified PCa diagnosed in white males in 2005 was compared to PCa screening rates on a state-by-state basis. To consider access to medical care and socioeconomic status, median family income, degree of urbanization, urologist population density and health insurance status were included in the analysis. PCa stage IV disease correlated inversely with PCa screening rates (r = -0.42, P = 0.006) where r is the correlation coefficient and P is the probability. Stage I PCa correlated with lack of health insurance (r = 0.37, P = 0.02). The results of this study suggest that with PCa screening may be associated with reduced rates of stage IV disease.

Effect of the correction for noncompliance and contamination on the estimated reduction of metastatic prostate cancer within a randomized screening trial (ERSPC section Rotterdam)

The European Randomized study of Screening for Prostate Cancer (ERSPC) has recently reported a 20% reduction in death from prostate cancer in a population-based prostate cancer screening (core age group: 55-69 years of age). The effect of screening may be diluted by noncompliance in the screening arm and contamination by PSA testing in the control arm. The purpose is to analyze the effect of prostate cancer screening on the incidence of metastatic prostate cancer, both with and without adjustment for noncompliance and contamination. We analyzed the occurrence of metastases in 42,376 men aged 55-75 years who were randomized in the Rotterdam section of the ERSPC between 1993 and 1999. Contamination adjustment was based on follow-up findings and questionnaire data from all men in the control group who developed prostate cancer and from a random sample of 291 men without cancer who had a PSA test. Prostate cancer screening significantly reduced the occurrence of metastatic prostate cancer in the intention-to-screen analysis [RR 0.75, 95% CI 0.59-0.95, p = 0.02] and more so in adjusted analyses; contamination adjusted RR 0.73, 95% CI 0.56-0.96; noncompliance adjusted RR 0.72, 95% CI 0.55-0.95 and fully adjusted analysis RR 0.68, 95% CI 0.49-0.94, p = 0.02. In the population of ERSPC Rotterdam (N = 42,376 men), screening reduces the risk to be diagnosed with metastatic prostate cancer considerably on population level, an effect which is even more pronounced in men who are in fact screened.

Risk of dying from prostate cancer in men randomized to screening

Although the true benefits and disadvantages of prostate cancer screening are still not known, the analysis of fatal cases is important for increasing knowledge of the effects of prostate cancer screening on mortality. Who dies from prostate cancer despite participation in a population-based prostate-specific antigen (PSA) screening program? From the Goteborg branch of the European Randomized study of Screening for Prostate Cancer, 10,000 men randomly assigned to active PSA-screening every second year formed the basis of the present study. Prostate cancer mortality was attributed to whether the men were attendees in the screening program (attending at least once) or nonattendees. Thirty-nine men died from prostate cancer during the first 13 years. Both overall (34% vs 13 %; P<.0001) and cancer-specific mortality (0.8% vs 0.3 %; P<.005) were found to be significantly higher among nonattendees compared with attendees. Furthermore, the majority of deaths (12 of 18) among screening attendees were in men diagnosed at first screening (prevalent cases). Only 6 deaths (including 3 interval cases) were noted among men complying with the biennial screening program. Nonattendees in prostate cancer screening constitute a high-risk group for both death from prostate cancer and death from other causes comparable to that described in other cancer screening programs.

PSA screening — a review of recent studies

In spite of the absence of level one evidence for its effectiveness, the use of screening has been prevalent worldwide with rates of around 70% in the US and 20– 40% in European countries. Prostate specific antigen (PSA) and digital rectal examination (DRE) are the most commonly applied screening tests. PSA was introduced into clinical medicine in 1987 and evidence for potential effectiveness in the early detection of prostate cancer emerged in the early 1990s after PSA driven biopsy indications revealed a significant down staging of prostate cancer at the time of diagnosis [ 1 Catalona WJ Smith DS Ratliff TL et al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med. 1991; 324: 1156-1161 Crossref PubMed Scopus (1840) Google Scholar ]. In the meantime, level one evidence for an effectiveness of prostate cancer screening in terms of lowering prostate cancer specific mortality has emerged [ 2 Schröder FH Hugosson J Roobol MJ et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009; 360: 1320-1328 Crossref PubMed Scopus (3135) Google Scholar ]. The findings of this study will be presented and discussed and put into perspective with other emerging evidence of the effects of prostate cancer screening on a population based and individual basis.

Screening for prostate cancer remains controversial

The effectiveness of prostate-cancer screening with prostate-specific antigen (PSA) for mortality reduction and quality-of-life improvement remains uncertain after the recent publication of two large trials—the European randomised study of screening for prostate cancer (ERSPC)1 and the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial.2,3