Prostate-Specific Antigen Screening in the United States vs in the European Randomized Study of Screening for Prostate Cancer–Rotterdam

Dissemination of prostate-specific antigen (PSA) testing in the United States coincided with an increasing incidence of prostate cancer, a shift to earlier stage disease at diagnosis, and decreasing prostate cancer mortality. We compared PSA screening performance with respect to prostate cancer detection in the US population vs in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC–Rotterdam). We developed a simulation model for prostate cancer and PSA screening for ERSPC–Rotterdam. This model was then adapted to the US population by replacing demography parameters with US-specific ones and the screening protocol with the frequency of PSA tests in the US population. We assumed that the natural progression of prostate cancer and the sensitivity of a PSA test followed by a biopsy were the same in the United States as in ERSPC–Rotterdam. The predicted prostate cancer incidence peak in the United States was then substantially higher than the observed prostate cancer incidence peak (13.3 vs 8.1 cases per 1000 man-years). However, the actual observed incidence was reproduced by assuming a substantially lower PSA test sensitivity in the United States than in ERSPC–Rotterdam. For example, for nonpalpable local- or regional-stage cancers (ie, stage T1M0), the estimates of PSA test sensitivity were 0.26 in the United States vs 0.94 in ERSPC–Rotterdam. We conclude that the efficacy of PSA screening in detecting prostate cancer was lower in the United States than in ERSPC–Rotterdam

All-cause mortality versus cancer-specific mortality as outcome in cancer screening trials: A review and modeling study

Background: All-cause mortality has been suggested as an end-point in cancer screening trials in order to avoid biases in attributing the cause of death. The aim of this study was to investigate which sample size and follow-up is needed to find a significant reduction in all-cause mortality. Methods: A literature review was conducted to identify previous studies that modeled the effect of screening on all-cause mortality. Microsimulation modeling was used to simulate breast cancer, lung cancer, and colorectal cancer screening trials. Model outputs were: cancer-specific deaths, all-cause deaths, and life-years gained per year of follow-up. Results: There were large differences between the evaluated cancers. For lung cancer, when 40 000 high-risk people are randomized to each arm, a significant reduction in all-cause mortality could be expected between 11 and 13 years of follow-up. For breast cancer, a significant reduction could be found between 16 and 26 years of follow-up for a sample size of over 300 000 women in each arm. For colorectal cancer, 600 000 persons in each arm were required to be followed for 15-20 years. Our systematic literature review identified seven papers, which showed highly similar results to our estimates. Conclusion: Cancer screening trials are able to demonstrate a significant reduction in all-cause mortality due to screening, but require very large sample sizes. Depending on the cancer, 40 000-600 000 participants per arm are needed to demonstrate a significant reduction. The reduction in all-cause mortality can only be detected between specific years of follow-up, more limited than the timeframe to detect a reduction in cancer-specific mortality

Availability of data for cost-effectiveness comparison of child vision and hearing screening programmes

Objective For cost-effectiveness comparison of child vision and hearing screening programmes, methods and data should be available. We assessed the current state of data collection and its availability in Europe. Methods The EUSCREEN Questionnaire, conducted in 2017–2018, assessed paediatric vision and hearing screening programmes in 45 countries in Europe. For the current study, its items on data collection, monitoring and evaluation, and six of eleven items essential for cost-effectiveness analysis: prevalence, sensitivity, specificity, coverage, attendance and loss to follow-up, were reappraised with an additional questionnaire. Results The practice of data collection in vision screening was reported in 36% (N = 42) of countries and in hearing screening in 81% (N = 43); collected data were published in 12% and 35%, respectively. Procedures for quality assurance in vision screening were reported in 19% and in hearing screening in 26%, research of screening effectiveness in 43% and 47%, whereas cost-effectiveness analysis was performed in 12% for both. Data on prevalence of amblyopia were reported in 40% and of hearing loss in 77%, on sensitivity of screening tests in 17% and 14%, on their specificity in 19% and 21%, on coverage of screening in 40% and 84%, on attendance in 21% and 37%, and on loss to follow-up in 12% and 40%, respectively. Conclusions Data collection is insufficient in hearing screening and even more so in vision screening: data essential for cost-effectiveness comparison could not be reported from most countries. When collection takes place, this is mostly at a local level for quality assurance or accountability, and data are often not accessible. The resulting inability to compare cost-effectiveness among screening programmes perpetuates their diversity and inefficiency

Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen

Background: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA.Methods: Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162).Results: If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality.Conclusions: Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening

Key indicators of organized cancer screening programs: Results from a Delphi study

Objective To maximize benefits and reduce potential harms of organized cancer screening programs in Europe, monitoring, quality assurance, and evaluation of long-term impact are required. We aimed to identify the most important indicators to be collected and reported. The study was designed to establish a consensus within a European-level working group and suggest a manageable list of key indicators. Methods We conducted a Delphi study among policymakers, researchers, and program coordinators who were experts in breast, cervical, or colorectal cancer screening. Study participants evaluated the importance of screening indicators on a 5-point Likert scale. Results The top 10 indicators by study participants were interval cancer rate, detection rate, screening attendance, screening coverage, cancer incidence

Modeled impact of intensified PSA screening in Black men

This dataset contains total prostate cancer diagnoses, screen diagnoses, and overdiagnoses per 1000 men under no screening and historical early detection strategies for all races and under no screening, historical, and intensified early detection strategies (by varying screening intervals, starting and stopping ages, and biopsy utilization following an abnormal PSA) for Black men in the United States projected by two models: the Fred Hutchinson Cancer Research Center ("FHCRC") and Erasmus Medical Center MIcrosimulation SCreening ANalysis ("MISCAN") models. The dataset also contains the estimated mean lead time ("MLT") for each early detection strategy and the estimated prostate cancer mortality reduction with 95% confidence intervals based on a combined analysis of the European Randomized Study of Screening for Prostate Cancer and the US-based Prostate, Lung, Colorectal, and Ovarian cancer screening trial

Modeled impact of intensified PSA screening in Black men

This dataset contains total prostate cancer diagnoses, screen diagnoses, and overdiagnoses per 1000 men under no screening and historical early detection strategies for all races and under no screening, historical, and intensified early detection strategies (by varying screening intervals, starting and stopping ages, and biopsy utilization following an abnormal PSA) for Black men in the United States projected by two models: the Fred Hutchinson Cancer Research Center ("FHCRC") and Erasmus Medical Center MIcrosimulation SCreening ANalysis ("MISCAN") models. The dataset also contains the estimated mean lead time ("MLT") for each early detection strategy and the estimated prostate cancer mortality reduction with 95% confidence intervals based on a combined analysis of the European Randomized Study of Screening for Prostate Cancer and the US-based Prostate, Lung, Colorectal, and Ovarian cancer screening trial

Personalized Biopsy Schedules Using an Interval-censored Cause-specific Joint Model

Active surveillance (AS), where biopsies are conducted to detect cancer progression, has been acknowledged as an efficient way to reduce the overtreatment of prostate cancer. Most AS cohorts use fixed biopsy schedules for all patients. However, the ideal test frequency remains unknown, and the routine use of such invasive tests burdens the patients. An emerging idea is to generate personalized biopsy schedules based on each patient's progression-specific risk. To achieve that, we propose the interval-censored cause-specific joint model (ICJM), which models the impact of longitudinal biomarkers on cancer progression while considering the competing event of early treatment initiation. The underlying likelihood function incorporates the interval-censoring of cancer progression, the competing risk of treatment, and the uncertainty about whether cancer progression occurred since the last biopsy in patients that are right-censored or experience the competing event. The model can produce patient-specific risk profiles until a horizon time. If the risk exceeds a certain threshold, a biopsy is conducted. The optimal threshold can be chosen by balancing two indicators of the biopsy schedules: the expected number of biopsies and expected delay in detection of cancer progression. A simulation study showed that our personalized schedules could considerably reduce the number of biopsies per patient by 34%-54% compared to the fixed schedules, though at the cost of a slightly longer detection delay