Screening Trial Research Articles

The American Cancer Society National Lung Cancer Roundtable strategic plan: Implementation of high-quality lung cancer screening.

More than a decade has passed since researchers in the Early Lung Cancer Action Project and the National Lung Screening Trial demonstrated the ability to save lives of high-risk individuals from lung cancer through regular screening by low dose computed tomography scan. The emergence of the most recent findings in the Dutch-Belgian lung-cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) further strengthens and expands on this evidence. These studies demonstrate the benefit of integrating lung cancer screening into clinical practice, yet lung cancer continues to lead cancer mortality rates in the United States. Fewer than 20% of screen eligible individuals are enrolled in lung cancer screening, leaving millions of qualified individuals without the standard of care and benefit they deserve. This article, part of the American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) strategic plan, examines the impediments to successful adoption, dissemination, and implementation of lung cancer screening. Proposed solutions identified by the ACS NLCRT Implementation Strategies Task Group and work currently underway to address these challenges to improve uptake of lung cancer screening are discussed. PLAIN LANGUAGE SUMMARY: The evidence supporting the benefit of lung cancer screening in adults who previously or currently smoke has led to widespread endorsement and coverage by health plans. Lung cancer screening programs should be designed to promote high uptake rates of screening among eligible adults, and to deliver high-quality screening and follow-up care.

Fertility and Miscarriage Incidence After Cervical Intraepithelial Neoplasia Treatment by Thermal Ablation: A Cohort Study.

To assess the impact of thermal ablation (TA) for the treatment of cervical dysplasia on fertility and pregnancy outcomes among women screened for cervical cancer in Cameroon. Retrospective cohort study. Dschang health district, Cameroon. Participants aged 30-45 years from two screening trials conducted between 2015 and 2020 in Dschang District Hospital. Participants were primarily screened for human papillomavirus infection, triaged by visual inspection and treated by TA if needed. Between October 2021 and March 2022, interviews on subsequent fertility were conducted with participants treated by TA and a control group of untreated women. Pregnancy and miscarriage after screening/treatment. A total of 760 participants (219 treated and 541 untreated) completed the survey, with a mean follow-up time of 1297 days. Sixty-two women (28.3%) treated by TA reported a pregnancy postscreening versus 165 (30.5%) in the control group (p = 0.550). Adjusted for potential confounders, the hazard ratio of pregnancy for treated compared with untreated women was 0.82 (0.54-1.24, p = 0.350). Among women reporting pregnancies with a known outcome and which were not voluntarily terminated, 18 (35.3%) treated participants had a miscarriage versus 31 (21.4%) in the control group (p = 0.048). In the adjusted model, no association remained between TA and miscarriage (1.04, 0.39-2.78, p = 0.935). In our study population, TA did not significantly impact fertility nor miscarriage risk. Our results support the widespread use of TA as a treatment of choice for precancerous cervical lesions in low-income settings.

The Azygos Esophageal Recess Is Not to Be Missed in Screening Lung Cancer With LDCT.

Lesion overlooking and late diagnostic workup can compromise the efficacy of low-dose CT (LDCT) screening of lung cancer (LC), implying more advanced and less curable disease stages. We hypothesized that the azygos esophageal recess (AER) of the right lower lobe (RLL) might be an area prone to lesion overlooking in LC screening. Two radiologists reviewed the LDCT examinations of all the screen-detected incident LCs observed in the active arm of 2 randomized clinical trials: ITALUNG and national lung screening trial. Those in the AER were compared with those in the remainder of the RLL for possible differences in diagnostic lag according to the Lung-RADS 1.1 recommendations, size, stage, and mortality. Six (11.7%) of 51 screen-detected incident LCs of the RLL were located in the AER. The diagnostic lag time was significantly longer (P=0.046) in the AER LC (mean 14±9mo) than in the LC in the remaining RLL (mean 7.3±1mo). Size and stage at diagnosis were not significantly different. All 6 subjects with LC in the AER and 16 (35.5%) of 45 subjects with LC in the remaining RLL (P=0.004) died of LC after a median follow-up of 12 years. Our retrospective study indicates that AER might represent a lung region of the RLL prone to have early LC overlooked due to detection or interpretation errors with possible detrimental consequences for the subject undergoing LC screening.

Cost-effectiveness analysis of a lung cancer screening program in the Netherlands: a simulation based on NELSON and NLST study outcomes

Background In the Netherlands, lung cancer is the leading cause of cancer-related death, accounting for more than 10,000 annual deaths. Lung cancer screening (LCS) studies using low-dose computed tomography (LDCT) have demonstrated that early detection reduces lung cancer mortality. However, no LCS program has been implemented yet in the Netherlands. A national LCS program has the potential to enhance the health outcomes for lung cancer patients in the Netherlands. Objective and Methods This study evaluates the cost-effectiveness of LCS compared to no-screening in the Netherlands, by simulating the screening outcomes based on data from NEderlands–Leuvens Longkanker Screenings ONderzoek (NELSON) and National Lung Screening Trial (NLST). We simulated annual screening up to 74 years of age, using inclusion criteria from the respective studies. A decision tree and Markov model was used to predict the incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICERs) for the screening population. The analysis used a lifetime horizon and a societal perspective. Results Compared to no-screening, LCS resulted in an ICER of €5,169 per QALY for the NELSON simulation, and an ICER of €17,119 per QALY for the NLST simulation. The screening costs were highly impactful for the cost-effectiveness. The most influential parameter was the CT scan cost. Cost reduction for CT from €201 to €101 per scan would reduce the ICER to €2,335 using NELSON criteria. Additionally, LCS could prevent 15,115 and 12,611 premature lung cancer deaths, accompanied by 1.66 and 1.31 QALYs gained per lung cancer case for the NELSON and NLST simulations, respectively. Conclusion LCS was estimated to be cost-effective in the Netherlands for both simulations at a willingness-to-pay threshold of €20,000 per QALY. Using the NELSON criteria, less than €5,500 per QALY had to be spent. Lowering the cost per CT exam would lead to a further reduction of this amount.

Increasing power in screening trials by testing control-arm specimens: application to multicancer detection screening.

Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the "intended effect" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests. We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial-colorectal component [PLCO-CRC]). Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 6-fold (NLST), 33-fold (MINN-FOBT-A), or 260 000-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 25% (NLST), 47% (MINN-FOBT-A), or 63% (PLCO-CRC). For potential MCD trial designs requiring 100 000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37 500-50 000 per arm, depending on assumptions concerning control-arm test-positives. Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests.

Retraction and Replacement of: Increasing power in screening trials by testing control-arm specimens: application to multicancer detection screening.

Retraction and Replacement of: Increasing power in screening trials by testing control-arm specimens: application to multicancer detection screening.

Pooling controls from nested case-control studies with the proportional risks model.

The standard approach to regression modeling for cause-specific hazards with prospective competing risks data specifies separate models for each failure type. An alternative proposed by Lunn and McNeil (1995) assumes the cause-specific hazards are proportional across causes. This may be more efficient than the standard approach, and allows the comparison of covariate effects across causes. In this paper, we extend Lunn and McNeil (1995) to nested case-control studies, accommodating scenarios with additional matching and non-proportionality. We also consider the case where data for different causes are obtained from different studies conducted in the same cohort. It is demonstrated that while only modest gains in efficiency are possible in full cohort analyses, substantial gains may be attained in nested case-control analyses for failure types that are relatively rare. Extensive simulation studies are conducted and real data analyses are provided using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) study.

“Mammograms are kind of my pacifier”: The cultural context of women's preference for annual mammograms in a risk-based screening cohort

Population genetic testing and risk-based screening have the potential to shift how we determine risk and screen for breast cancer. While much attention has been paid to the experiences of individuals who may be at elevated risk for breast cancer, less is known about how those at average risk make decisions about their health. Through qualitative interviews with 30 participants, we explore how those enrolled in a risk-based screening trial who are determined to be at average risk for breast cancer make screening decisions. We consider how the social context of breast health, known as ‘pink ribbon culture,’ and the pervasiveness of annual mammography as the standard of care make risk-based screening less acceptable for many participants. Risk-based screening paradigms assume that individuals will assess their risk quantitatively based on the risk models that are used. Yet, our findings demonstrate that social and cultural factors influence decision-making surrounding breast cancer screening, an important consideration when implementing risk-based screening programs. We will begin to address a gap in knowledge about how women who are told they are average risk after risk-based screening (most of the population) and recommended to screen less than annually make screening decisions.

Associations of minerals intake with colorectal cancer risk in the prostate, lung, colorectal, ovarian cancer screening trial.

Exploring the association between common mineral intake and the risk of colorectal cancer (CRC). We utilized the multivariate Cox proportional hazards model to assess the association between intake of minerals and the risk of CRC, estimating hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 101,686 eligible participants were included in the analysis of this study, including 1,100 CRC cases. After adjusting for potential confounders, we found that total zinc intake (HRQ4vs.Q1: 0.79, 95%CI 0.67-0.93; P for trend <0.05), iron intake (HRQ4vs.Q1: 0.81, 95%CI 0.68-0.96; P for trend <0.05), copper intake (HRQ4vs.Q1: 0.80, 95%CI 0.68-0.95; P for trend <0.05), selenium intake (HRQ4vs.Q1: 0.83, 95%CI 0.69-0.98; P for trend <0.05) were significantly negatively associated with the incidence of CRC, but magnesium intake in the appropriate range is associated with a reduced risk of CRC (HRQ3vs.Q1: 0.77, 95%CI 0.65-0.91; P for trend >0.05). Our findings suggested that an appropriate intake of total zinc, iron, copper, selenium and magnesium were associated with lower CRC risk.

Developing a Conceptual Framework for a Person-Centered Approach to Improving Adherence and Outcomes in Lung Cancer Screening: The Engaged Approach to Lung Cancer Screening: A Brief Report

IntroductionTranslating outcomes from randomized trials of lung cancer screening into community practice settings has been challenging. We developed a framework—the Engaged Approach to Lung Cancer Screening (EA-LCS)—for improving adherence and individual and population health outcomes in LCS. MethodsEmploying community-engaged research, we conducted semistructured interviews with LCS program staff (N = 15) and participants (N = 7) and administered brief surveys to understand LCS adherence. We combined our knowledge of LCS implementation with data to formulate the EA-LCS framework, including principles and strategies instrumental for LCS adherence. ResultsProgram staff identified four factors that facilitated adherence: (1) the use of specialized tracking software, (2) the importance of personal connection and a reliable touchpoint, (3) centralized program operations, and (4) standardization/streamlining of reports to participants and clinicians. Participant data identified four factors supporting adherence: (1) a single contact point and information availability, (2) tailored communications, (3) personalized results delivery, and (4) increased scan accessibility. Combined analyses identified three overarching themes in the EA-LCS framework: (1) respect, (2) trust, and (3) engagement. ConclusionsThe EA-LCS conceptual model integrates three foundational principles (person-centeredness, trustworthy relationships, and sustained communications) to enhance LCS adherence. Efforts are underway to translate the EA-LCS framework into materials to support adherence.

Randomized Invitation to Systematic NT-proBNP and ECG Screening in 75-Year Olds to Detect Atrial Fibrillation -STROKESTOP II.

Background: Guidelines have suggested screening for atrial fibrillation to enable early treatment and avoid downstream negative clinical events. We aimed to determine if atrial fibrillation screening potentially enhanced by NT-proBNP would reduce stroke or systemic embolism incidence as compared to in a control group and to determine if it was safe for those with low NT-proBNP concentrations to forfeit prolonged screening. Methods: In this randomized controlled trial all 75/76-year-old individuals in Stockholm Region, Sweden were randomized 1:1 to be invited to screening or serve as a control group. NT-proBNP concentration were measured and a single-lead-ECG registered only once if NT-proBNP<125ng/L, whereas if NT-proBNP≥125 ng/L participants underwent prolonged screening, recording single-lead ECGs four times daily for two weeks. If atrial fibrillation was detected, treatment was initiated. Baseline and outcome data were collected from Swedish National Registries. Results: In total 28,712 individuals were randomized, after exclusion of death and emigration 13,905 remained in the intervention group, 13,884 in the control group. Participation rate in the intervention group was 49.2% (6,843/13,905). Participants in the high NT-proBNP group (NT-proBNP≥125 ng/L) without prior atrial fibrillation constituted 60% of the total and underwent prolonged screening. New AF was detected in 2.4% (165/6,843) in the intervention group. There was no difference in AF prevalence or oral anticoagulant treatment between the intervention and the control group after five years follow-up. After a median of 5.1 years (IQR 5.0-5.8) there was no difference in the primary outcome of stroke or systemic embolism between the intervention group and the control group, HR: 0.96 (95% CI 0.86-1.06). The low NT-proBNP-group had significantly fewer strokes or systemic emboli than the control group, HR: 0.59 (95% CI 0.46-0.74), p<0.001. In the high NT-proBNP group the risk of stroke or systemic embolism was higher compared to the low NT-proBNP group, HR: 1.57 (95% CI 1.22-2.02), p=0.001. Conclusions: In this population-based screening trial for atrial fibrillation using NT-proBNP for screening enhancement, there was no difference in risk of stroke or systemic embolism for the intervention group compared to controls. Participation was moderate. The use of NT-proBNP for screening enhancement was safe in identifying low-risk participants. Clinical Trial Registration: www.clinicaltrials.gov; NCT02743416.

AI for Multistructure Incidental Findings and Mortality Prediction at Chest CT in Lung Cancer Screening.

Background Incidental extrapulmonary findings are commonly detected on chest CT scans and can be clinically important. Purpose To integrate artificial intelligence (AI)-based segmentation for multiple structures, coronary artery calcium (CAC), and epicardial adipose tissue with automated feature extraction methods and machine learning to detect extrapulmonary abnormalities and predict all-cause mortality (ACM) in a large multicenter cohort. Materials and Methods In this post hoc analysis, baseline chest CT scans in patients enrolled in the National Lung Screening Trial (NLST) from August 2002 to September 2007 were included from 33 participating sites. Per scan, 32 structures were segmented with a multistructure model. For each structure, 15 clinically interpretable radiomic features were quantified. Four general codes describing abnormalities reported by NLST radiologists were applied to identify extrapulmonary significant incidental findings on the CT scans. Death at 2-year and 10-year follow-up and the presence of extrapulmonary significant incidental findings were predicted with ensemble AI models, and individualized structure risk scores were evaluated. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the performance of the models for prediction of ACM and extrapulmonary significant incidental findings. The Pearson χ2 test and Kruskal-Wallis rank sum test were used for statistical analyses. Results A total of 24 401 participants (median age, 61 years [IQR, 57-65 years]; 14 468 male) were included. In 3880 of 24 401 participants (16%), 4283 extrapulmonary significant incidental findings were reported. During the 10-year follow-up, 3389 of 24 401 participants (14%) died. CAC had the highest feature importance for predicting the three study end points. The 10-year ACM model demonstrated the best AUC performance (0.72; per-year mortality of 2.6% above and 0.8% below the risk threshold), followed by 2-year ACM (0.71; per-year mortality of 1.13% above and 0.3% below the risk threshold) and prediction of extrapulmonary significant incidental findings (0.70; probability of occurrence of 25.4% above and 9.6% below the threshold). Conclusion A fully automated AI model indicated extrapulmonary structures at risk on chest CT scans and predicted ACM with explanations. ClinicalTrials.gov Identifier: NCT00047385 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Yanagawa and Hata in this issue.

Glucose levels at hospital admission are associated with 5 year mortality

AimWe aimed to determine if hospital admission hyperglycaemia and hypoglycaemia are associated with increased long-term mortality. MethodsA post-hoc analysis of data from a trial of glucose screening in the emergency department was conducted. Data were linked with a death registry up to 5 years after admission. The relationship between admission glucose and mortality was examined by cox regression. Further analyses of people who survived the admission and subsequent 28 days was performed. ResultsThere were 131,322 patients, of whom 38,712 (29.5 %) died. Mean follow-up was 3·3 ± 1·5 years. Compared to the reference glucose band of 6·1-8·0 mmol/L, there was increased mortality in higher bands, reaching a hazard ratio (HR) of 1·44 (95 %CI 1·34-1·55, p < 0·001) for people with glucose > 20·0 mmol/L. The HR was 1·56 (95 %CI 1·46-1·68, p < 0·001) for people with glucose ≤ 4·0 mmol/L. Similar relationships were observed among 28-day survivors. The relationships were attenuated among people with known diabetes.Among 4867 subjects with glucose ≥ 14·0 mmol/L, those diagnosed with diabetes during the admission had lower mortality compared to subjects where the diagnosis was not made (HR 0·53, 95 %CI 0·40-0·72, p < 0·001). This was attenuated among 28-day survivors. ConclusionHyperglycaemia and hypoglycaemia on hospital admission are associated with increased long-term mortality.

Identifying a Heterogeneous Effect of Atrial Fibrillation Screening in Older Adults: A Secondary Analysis of the VITAL-AF Trial.

One-time atrial fibrillation (AF) screening trials have produced mixed results; however, it is unclear if there is a subset for whom screening is effective. Identifying such a subgroup would support targeted screening. We conducted a secondary analysis of VITAL-AF, a randomized trial of one-time, single-lead ECG screening during primary care visits. We tested two approaches to identify a subgroup where screening is effective. First, we developed an effect-based model using a T-learner. Specifically, we separately predicted the likelihood of AF diagnosis under screening and usual care conditions; the difference in probabilities was the predicted screening effect. Second, we used a validated AF risk model to test for a heterogeneous screening effect. We used interaction testing to determine if observed AF diagnosis rates in the screening and usual care groups differed when stratified by decile of the predicted screening effect and predicted AF risk. Baseline characteristics were similar between the screening (n=15187) and usual care (n=15078) groups (mean age 74 years, 59% female). In the effect-based analysis, in the highest decile of predicted screening effectiveness (n=3026), AF diagnosis rates were higher in the screening group (6.50 vs. 3.06 per 100 person-years, rate difference 3.45, 95%CI 1.62 to 5.28). In this group, the mean age was 84 years and 68% were female. The risk-based analysis did not identify a subgroup where screening was more effective. Predicted screening effectiveness and predicted baseline AF risk were poorly correlated (Spearman coefficient 0.13). In a secondary analysis of the VITAL-AF trial, we identified a small subgroup where one-time screening was associated with increased AF diagnoses using an effect-based approach. In this study, predicted AF risk was a poor proxy for predicted screening effectiveness. These data caution against the assumption that high AF risk is necessarily correlated with high screening effectiveness.

Risk-stratified screening and colorectal cancer incidence and mortality: A retrospective study from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

ObjectiveTo determine whether risk stratification can optimize the benefits of flexible sigmoidoscopy (FSG) screening. MethodsThe Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted from 1993 to 2001 in the United States. A colorectal cancer (CRC) risk stratification tool was developed in the control arm (n = 64,207) from the PLCO cohort and validated in the UK Biobank (n = 270,726). PLCO participants (n = 130,021) were classified into low-, medium-, and high-risk groups. Cumulative incidence and mortality were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between screening and CRC incidence and mortality. ResultsThe CRC risk stratification tool was based on age, gender, body mass index, smoking status, family history of CRC, diabetes, regular use of aspirin, and CRC screening history. Compared with the control arm, FSG screening was significantly associated with a reduction in mortality in both the medium-risk (HR = 0.76, 95% CI = 0.63–0.92) and high-risk groups (0.58, 0.46–0.73), but not in the low-risk group (0.85, 0.61–1.19). FSG screening also reduced distal CRC incidence and mortality in the medium-risk and high-risk groups. Furthermore, it was associated with a reduction in incidence (0.74, 0.59–0.92) and mortality (0.59, 0.40–0.87) of proximal colon cancer in the high-risk group. ConclusionsFSG screening yielded more benefits for the high-risk group than for the low-risk and medium-risk groups, supporting the development of a risk-stratified CRC screening strategy.

OS IMPACTOS DAS TÉCNICAS DE RASTREIO DE CA DE PULMÃO E SEU IMPACTO NA MORTALIDADE NA POPULAÇÃO TABAGISTA

To present the theme of the impacts of lung cancer screening and its impact on mortality in the smoking population. Lung cancer is the neoplasm with the highest incidence and mortality in the world. Its natural history is characterized by rapid progression and late diagnosis, which limits therapeutic options and causes low patient survival. The objective of this work is to reflect on the possibilities of increasing the number of early diagnoses in order to decrease mortality and improve survival for lung cancer. The follow-up of lung cancer with low-dose computed tomography (LDCT), for example, has been shown in the National Lung Screening Trial (NLST) and NELSON studies to increase the number of early stage diagnoses and reduce lung cancer mortality by over 20%. Screening measures have shown to be favorable for asymptomatic patients at high risk of neoplasia, contributing to a favorable prognosis. LDCT is the main screening tool, with higher sensitivity in the early detection of lung neoplasia and stage I cancer compared to chest X-ray screening. In this article, we compare the results established in each study in order to reflect on the need for investment in lung cancer screening.

How a population-based cohort of men estimate lifetime risk of prostate cancer in a survey before entering a prostate cancer screening trial in Sweden?

ObjectivesInvestigating men’s perceived lifetime risk of prostate cancer.DesignSurvey-based study to men invited for prostate-specific antigen (PSA) screening in the GÖTEBORG-2 trial between September 2015 and June 2020.Setting38 775 men in...

Re: Prostate Cancers in the Prostate-specific Antigen Interval of 1.8-3 ng/ml: Results from the Göteborg-2 Prostate Cancer Screening Trial

Re: Prostate Cancers in the Prostate-specific Antigen Interval of 1.8-3 ng/ml: Results from the Göteborg-2 Prostate Cancer Screening Trial

Nationwide registry-based trial of risk-stratified cervical screening.

In well-screened populations, most cervical cancers arise from small groups of women with inadequate screening. The present study aims to assess whether registry-based cancer risk assessment could be used to increase screening intensity among high-risk women. The National Cervical Screening Registry identified the 28,689 women residents in Sweden who had either no previous cervical screening or a screening history indicating high risk. We invited these women by SMS and/or physical letter to order a free human papillomavirus (HPV) self-sampling kit. The Swedish national HPV reference laboratory performed extended HPV genotyping and referred high-risk HPV-positive women to their regional gynecologist. A total of 3691/28,689 (12.9%) women ordered a self-sampling kit and 10.0% (2853/28,689) returned a sample for testing. Participation among women who had never attended screening was low, albeit improved. Up to 22.5% of women in other high-risk groups attended. High-risk HPV types were detected in 8.3% of samples. High-risk HPV-positive women (238/2853) were referred without further triaging and severe cervical precancer or cancer (HSIL+) in histopathology were detected in 36/158 (23%) of biopsied women. Repeat invitations gave modest additional participation. Nationwide contacting of women with high risk for cervical cancer with personal invitations to order HPV self-sampling kits resulted in high yield of detected CIN2+. Further efforts to improve risk-stratified screening strategies should be directed to improving (i) the precision of the risk-stratification algorithm, (ii) the convenience for the women to participate and, (iii) ensuring that screen-positive women are followed-up.

Will DANCAVAS be the most important screening trial in the last 50 years?

Screening trials for cardiovascular disease have not demonstrated a reduction in all-cause mortality. The Danish Cardiovascular Screening trial (DANCAVAS) involved men aged 65–74 years old who were randomized to an invitation to undergo screening or not. While the 5-year interim analysis did not show a statistically significant benefit in the primary outcome of all-cause mortality, HR 0.95 (CI 0.90–1.00), a sub-group analysis of men age 65–69 did show a lower hazard ratio of 0.89 (CI 0.83–0.96). Given the widening difference between screened and un-screened participants, as well as the benefit in younger subjects, it is likely that the next analysis will demonstrate a statistically-significant benefit of screening. In this commentary we argue why this trial will almost certainly become one of the most influential screening trials and why heeding its most important lesson, the use of coronary artery calcium scoring, has the potential to save countless lives.