Population-based Screening Trial Research Articles

Absolute risk prediction for esophageal squamous cell carcinoma adaptable to regional disease burden across diverse regions.

Esophageal squamous cell carcinoma (ESCC) exhibits a long latency period and has a significant geographical disparity in incidence, which underscores the need for models predicting the long-term absolute risk adaptable to regional disease burden. 31,883 participants in a large-scale population-based screening trial (Hua County, China) were enrolled to develop the model. Severe dysplasia and above (SDA) identified at screening or follow-up were defined as the outcome. We calculated the absolute risk in three steps: 1) constructing a relative risk model using logistic regression, 2) calculating the age-specific baseline hazard, and 3) adjusting for the competing risk of all-cause death excluding ESCC. Flexible incidence rate parameters were integrated into the model to ensure its relevance across diverse regions worldwide. A total of 295 SDAs were detected. The relative risk model consisted of old age, male gender, irregular meal pattern, preference for hot or hard food, BMI of less than 22 kg/m2, and ESCC family history. The area under the receiver operating characteristic curve was 0.753 (95% CI: 0.749-0.757). The averaged 5-year and 10-year absolute risk were 0.53% and 1.30% among participants. Based on our model, we developed an online calculator incorporated flexible incidence rate parameters, demonstrating ideal risk stratification tailored to regions with varying disease burdens (https://pkugenetics.shinyapps.io/escc_risk_prediction/). We developed an absolute risk model to predict individualized long-term risk of ESCC, accounting for local disease burden. This model has the potential to mitigate the global burden of ESCC by enabling targeted screening and personalized prevention strategies.

Our journey toward implementation of digital breast tomosynthesis in breast cancer screening: the Malmö Breast Tomosynthesis Screening Project.

The purpose is to describe the Malmö Breast Tomosynthesis Screening Project from the beginning to where we are now, and thoughts for the future. In two acts, we describe the efforts made by our research group to improve breast cancer screening by introducing digital breast tomosynthesis (DBT), all the way from initial studies to a large prospective population-based screening trial and beyond. Our studies have shown that DBT has significant advantages over digital mammography (DM), the current gold standard method for breast cancer screening in Europe, in many aspects except a major one-the increased radiologist workload introduced with DBT compared with DM. It is foreseen that AI could be a viable solution to overcome this problem. We have proved that one-view DBT is a highly efficient screening approach with respect to diagnostic performance.

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

Guidelines have suggested screening for atrial fibrillation to enable early treatment and avoid downstream negative clinical events. We aimed to determine whether atrial fibrillation screening potentially enhanced by NT-proBNP (N-terminal pro-B-type natriuretic peptide) would reduce stroke or systemic embolism incidence compared with a control group and to determine whether it was safe for those with low NT-proBNP concentrations to forfeit prolonged screening. In this randomized controlled trial, all 75- and 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 concentrations were measured, and a single-lead ECG was registered only once if NT-proBNP <125 ng/L, whereas if NT-proBNP ≥125 ng/L, participants underwent prolonged screening, recording single-lead ECGs 4 times daily for 2 weeks. If atrial fibrillation was detected, treatment was initiated. Baseline and outcome data were collected from Swedish National Registries. 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. The participation rate in the intervention group was 49.2% (6843 of 13 905). Participants in the high NT-proBNP group (NT-proBNP≥125 ng/L) without previous atrial fibrillation constituted 60% of the total and underwent prolonged screening. New atrial fibrillation was detected in 2.4% (165 of 6843) in the intervention group. There was no difference in atrial fibrillation prevalence or oral anticoagulant treatment between the intervention and the control group after 5 years of follow-up. After a median of 5.1 years (interquartile range, 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 (hazard ratio, 0.96 [95% CI, 0.86-1.06]). The low NT-proBNP group had significantly fewer strokes or systemic emboli than the control group (hazard ratio, 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 with the low NT-proBNP group (hazard ratio, 1.57 [95% CI, 1.22-2.02]; P=0.001). 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 with controls. Participation was moderate. The use of NT-proBNP for screening enhancement was safe in identifying low-risk participants. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02743416.

Persistence of Lugol-unstaining is Associated With an Increased Risk of Progression to Malignancy in the Esophagus

Background and aimsTo investigate the persistence of Lugol-unstained lesions (LULs) in the esophagus detected by chromoendoscopy and explore its association with progression to malignancy. MethodsWe enrolled 647 participants from a population-based screening trial who had biopsied LULs at the baseline chromoendoscopy and underwent a chromoendoscopy reexamination after a median of 4.39 years. Cases of persistent LUL were defined as those in whom a visible LUL was observed during reexamination at the documented location (±2cm) where a LUL was detected at baseline chromoendoscopy. Logistic regression was applied to explore risk factors for the persistence of LULs. The primary outcome was clinical-stage esophageal squamous cell carcinoma (ESCC) identified over 6.78 years of follow-up and the secondary outcome was reexamination-detected severe dysplasia and above lesions (SDA). The cumulative incidence was calculated to assess the progression risk associated with the persistence of LULs. ResultsThe proportion of participants with persistent LULs was 81.92%. Dysplasia (adjusted OR=6.16, 95%CI: 2.70 to 17.80), large LULs (adjusted OR=1.90, 95%CI: 1.18 to 3.15), and irregularly shaped LULs (adjusted OR=1.63, 95%CI: 1.03 to 2.56) at baseline were associated with an increased risk of LUL persistence. Eleven clinical-stage ESCC cases and 31 SDAs detected during reexamination were identified, all of which originated from patients with persistent LULs (Pclinical-stageESCC =0.136, Preexamination-detected SDA =0.015). ConclusionThe persistence of LULs is associated with progression to malignancy in the esophagus, even in individuals without dysplastic lesions. Based on this, a more efficient post-screening surveillance strategy could be established.

Developing an optimal stratification model for colorectal cancer screening and reducing racial disparities in multi-center population-based studies

BackgroundEarly detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population.MethodsTo develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS148); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS183); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRSGenomewide). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants.ResultsThree trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS183 demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose–response effect of PRS183 on incident colorectal neoplasms. Incorporating PRS183 with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32).ConclusionsOur comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity.Graphical

Colposcopy Referral and CIN3+ Risk of Human Papillomavirus Genotyping Strategies in Cervical Cancer Screening.

High-risk human papillomavirus (hrHPV)-based cervical cancer screening in the Netherlands led to a substantial increase in number of colposcopy referrals and low-grade lesions detected. Genotyping strategies may be employed to lower the screening-related burden. We evaluated 14 triage strategies with genotyping (HPV16/18 or HPV16/18/31/33/45/52/58) for hrHPV-positive borderlineormilddyskaryosis (BMD)ornormal cytology,usingdata from a population-based hrHPV-based screening trial with 5-year interval (POBASCAM). We considered colposcopy referral at baseline, after 6-month repeat cytology and after 5-year hrHPV testing. Performance was evaluated by one-round positive and negative predictive value (PPVandNPV) for CIN3+ and by two-roundcolposcopy referral rate. To identify efficient strategies, they were ordered by the one-round colposcopy referral rate. Adjacent strategies were compared by the marginal PPV for detecting one additional CIN3+ (mPPV). The most conservative strategy (repeat cytology after BMD and HPV16/18/31/33/45/52/58-positive normal cytology, next round otherwise) yielded an mPPV of 28%, NPV of 98.2%, and two-round colposcopy referral rate of 47.2%. Adding direct referral after BMD or genotype-positive BMD yielded an mPPV ≤ 8.2%, NPV ≥ 98.5% and an increase in colposcopy referral rate of 1.9% to 6.5%. Adding direct referral after HPV16/18-positive normal cytology yielded an mPPV ≤ 3.5%, NPV ≥ 99.5% and an increase in colposcopy referral rate of 13.9%. Direct colposcopy referral of women with BMD or normal cytology is unlikely to be efficient, but genotype-guided direct referral after BMD may be considered because the increase in colposcopies is limited. hrHPV screening programs can become very efficient when immediate colposcopy referral is limited to women at highest CIN3+ risk. See related In the Spotlight, p. 979.

How should extra-large Lugol-unstained lesions of the esophagus be treated? Results from a population-based cohort study.

Current guidelines recommend only severe dysplasia and above (SDA) lesions of the esophageal squamous epithelium for clinical intervention. However, the histopathologic diagnosis derived from tissue biopsies may be subject to underestimation of severity. 1073 participants from whom biopsies were taken at baseline chromoendoscopic examination in a population-based screening trial were enrolled in this study. The size of the Lugol-unstained lesions (LULs) was mainly analyzed. The outcome was defined as SDA lesions either identified at baseline screening, or during follow-up, collectively referred to as the cumulative risk of SDA. Multivariable logistic regression models were used to evaluate the cumulative risk of SDA. One hundred and forty-six SDA cases were identified in the study period. Participants with large LULs had a high cumulative incidence of SDA (cumulative incidence16-20mm : 55.88%; cumulative incidence>20mm : 76.92%) in the median of 7-year duration. LULs of large size were significantly associated with a higher cumulative risk of SDA, regardless of the pathologic diagnosis (adjusted OR16-20mmvs.≤5mm = 21.02, 95% CI: 7.56-58.47; adjusted OR>20mmvs.≤5mm = 33.62, 95% CI: 11.79-95.87). Results from this study suggest physician-patient shared decision-making regarding clinical treatment or intensive surveillance should be carried out for LULs >20 mm in the esophagus, regardless of the histologic diagnosis. For those with LULs of 16-20 mm, intensive surveillance would also best be considered.

Relationship Between Baseline Prostate-specific Antigen on Cancer Detection and Prostate Cancer Death: Long-term Follow-up from the European Randomized Study of Screening for Prostate Cancer

BackgroundThe European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age. ObjectiveTo analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2–4 yr). Design, setting, and participantsWe evaluated 25589 men aged 55–59 yr, 16898 men aged 60–64 yr, and 12936 men aged 65–69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2–4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU). Outcome measurements and statistical analysisWe assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason ≥7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA and PCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60–61 yr. Results and limitationsThe overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial probability of csPCa at 16 yr ranged from 1.2–1.5% for men with PSA <1.0 ng/ml to 13.3–13.8% for men with PSA ≥3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60–61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ml). In addition, for men initially screened at age 60–61 yr with baseline PSA <2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68–70 yr if PSA is still <2 ng/ml. No case of PCSM emerged in the subsequent 8 yr (up to age 76–78 yr). A limitation is that these results may not be generalizable to an opportunistic screening setting or to contemporary clinical practice. ConclusionsIn all age groups, baseline PSA can guide decisions on the repeat screening interval. Baseline PSA of <1.0 ng/ml for men aged 55–69 yr is a strong indicator to delay or stop further screening. Patient summaryIn prostate cancer screening, the patient’s baseline PSA (prostate-specific antigen) level can be used to guide decisions on when to repeat screening. The PSA test when used according to current knowledge is valuable in helping to reduce the burden of prostate cancer.

PD38-11 THE STOCKHOLM3 PROSTATE CANCER SCREENING TRIAL (STHLM3): AN INTERIM ANALYSIS OF MORTALITY RESULTS AFTER 6.5 YEARS OF FOLLOW-UP

You have accessJournal of UrologyCME1 Apr 2023PD38-11 THE STOCKHOLM3 PROSTATE CANCER SCREENING TRIAL (STHLM3): AN INTERIM ANALYSIS OF MORTALITY RESULTS AFTER 6.5 YEARS OF FOLLOW-UP Chiara Micoli, Alessio Crippa, Andrea Discacciati, Thorgerdur Palsdottir, Hari Vigneswaran, Markus Aly, Jan Adolfsson, Johan Lindberg, Peter Wiklund, James Thompson, Yvonne Brandberg, Mark Clements, Lars Egevad, Henrik Grönberg, Tobias Nordström, and Martin Eklund Chiara MicoliChiara Micoli More articles by this author , Alessio CrippaAlessio Crippa More articles by this author , Andrea DiscacciatiAndrea Discacciati More articles by this author , Thorgerdur PalsdottirThorgerdur Palsdottir More articles by this author , Hari VigneswaranHari Vigneswaran More articles by this author , Markus AlyMarkus Aly More articles by this author , Jan AdolfssonJan Adolfsson More articles by this author , Johan LindbergJohan Lindberg More articles by this author , Peter WiklundPeter Wiklund More articles by this author , James ThompsonJames Thompson More articles by this author , Yvonne BrandbergYvonne Brandberg More articles by this author , Mark ClementsMark Clements More articles by this author , Lars EgevadLars Egevad More articles by this author , Henrik GrönbergHenrik Grönberg More articles by this author , Tobias NordströmTobias Nordström More articles by this author , and Martin EklundMartin Eklund More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003336.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer screening is controversial due to high rates of overdiagnosis. The population-based screening trial STHLM3 utilized a single prostate-specific antigen (PSA) and Stockholm3 test (a prediction model based on clinical variables, blood biomarkers, and a polygenic risk score) to identify Gleason score ≥7 prostate cancer. In an interim analysis after 6.5 years of follow-up, we compared prostate cancer specific and all-cause mortality in men invited to STHLM3 to men not invited. METHODS: STHLM3 was conducted 2012-2015. Men 50-70 years of age residing in Stockholm, Sweden, were randomly invited from the general population to undergo prostate cancer testing. Men with PSA ≥3 ng/ml or Stockholm3 ≥10% were recommended prostate biopsy. We calculated cumulative incidences and risk ratios (RR) of prostate cancer diagnosis, prostate cancer mortality, and any-cause mortality after 6.5 years of follow-up in men invited to STHLM3 vs. not invited (intention-to-screen analysis). Alpha spending adjusted two-sided 98% confidence intervals were computed. RESULTS: In total, 245,905 men were eligible for STHLM3; 168,707 (69.6%) were randomly invited and 70,297 (29.4%) were not invited. Of invited men, 58,909 (35%) participated and 109,798 (65%) did not.After 6.5 years of follow-up, 91 men died of prostate cancer among men invited to STHLM3 vs. 51 among men not invited (RR 0.76; 98% CI 0.50 to 1.14). The number of prostate cancer diagnoses was higher among men invited to STHLM3 (n=5310) vs. not invited (n=1742) (RR 1.21; 98% CI 1.15 to 1.29). For all-cause mortality, there were 7784 deaths among men invited to STHLM3 vs. 3189 deaths among men not invited (RR 1.03; 98% CI 0.98 to 1.08). CONCLUSIONS: These results may cautiously suggest a potential effect on reducing prostate cancer mortality after 6.5 years of follow-up by a single intensive screening intervention using PSA and Stockholm3 in combination, to the cost of increased prostate cancer incidence. Longer-term follow-up is needed and is underway. Source of Funding: Swedish Research Council, Swedish Cancer Society © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e997 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chiara Micoli More articles by this author Alessio Crippa More articles by this author Andrea Discacciati More articles by this author Thorgerdur Palsdottir More articles by this author Hari Vigneswaran More articles by this author Markus Aly More articles by this author Jan Adolfsson More articles by this author Johan Lindberg More articles by this author Peter Wiklund More articles by this author James Thompson More articles by this author Yvonne Brandberg More articles by this author Mark Clements More articles by this author Lars Egevad More articles by this author Henrik Grönberg More articles by this author Tobias Nordström More articles by this author Martin Eklund More articles by this author Expand All Advertisement PDF downloadLoading ...

Multiple Lugol-unstained lesions predict higher cumulative risk of malignance in the esophagus.

The impact of the presence of multiple Lugol-unstained lesions (LULs) in the esophagus on the risk of having severe dysplasia and above (SDA) lesions among asymptomatic individuals is unknown. We collected demographic factors, behavioral variables, and features of LULs from 1073 participants who were biopsied at baseline endoscopic screening in a population-based screening trial, and these individuals were followed over a median time of 7years. Outcome events were defined as SDA identified at screening, at reexamination, or during follow-up. "Multiple LULs" were defined as ≥2 LULs found in the entirety of the esophagus. Multivariable logistic regression models were fitted to assess the effect of "multiple LULs" on the cumulative risk of SDA. There were 147 SDA cases in the current study. After adjustment for potential risk factors and endoscopic features of LULs, the presence of "multiple LULs" slightly increased the cumulative risk of having SDA with no statistical significance (adjusted odds ratio [OR]=1.26; 95% confidence interval [CI] [0.85, 1.88]). Further stratified analysis showed that this association was strong among subjects with small LULs (≤5mm) (adjusted OR=3.29; 95% CI [1.39, 7.79]). However, no such association was observed in subjects with larger LULs (adjusted OR=0.99; 95% CI [0.63, 1.55], P interaction =0.022). The presence of "multiple small LULs (≤5mm)" in chromoendoscopy indicates a higher cumulative risk of having SDA in the esophagus. We recommend biopsies be taken and surveillance be maintained at a more active level in individuals with relatively small but multiple LULs.

Head-to-head comparison of a risk-adapted screening strategy using various risk prediction models in detecting colorectal neoplasm.

The risk-adapted screening strategy showed satisfying colorectal cancer (CRC) screening yield and efficiency. We therefore further explored the diagnostic performance variation of this strategy using different risk prediction models. A literature search was conducted to identify studies evaluating risk models for advanced colorectal neoplasm (ACN). The included models were retrospectively validated in a subset sample (N=3219) from a population-based CRC screening trial in China. Diagnosis-related indictors were compared between the risk-adapted screening strategy using different models and the fecal immunochemical test (FIT)-only strategy. For simulated populations with ACN prevalence of 3% to 12%, the trade-off of additional false positives for each additional true positive were calculated. We included 14 eligible risk models with the area under the curves ranging 0.570 to 0.652 in the validation set. The overall sensitivities of the risk-adapted screening strategy using different risk models for ACN varied from 46.0% to 69.8%, higher than FIT (21.9%), but at the expense of specificities (51.6% to 78.3% vs 97.1%). For population having ACN prevalence of 3%, risk-adapted screening strategies needed 20.5 to 31.1 additional false positives for each additional true positive compared with FIT, and respective number would substantially reduce (4.7 to 7.1) as the ACN prevalence increased to 12%. Risk-adapted screening strategy using the current risk models showed improved sensitivity for ACN compared with FIT, at the cost of increased colonoscopy workload. The optimal strategy for screening practice should be tailored considering the disease burden and availability of healthcare resources.

The Association Between Age, Prostate Cancer Risk, and Higher Gleason Score in a Long-term Screening Program: Results from the Göteborg-1 Prostate Cancer Screening Trial

BackgroundStudies have suggested associations between greater age, increased risk of prostate cancer (PC), and higher Gleason score. ObjectiveThe present study aimed at investigating these associations within the Göteborg-1 randomized, population-based PC screening trial. Design, setting, and participantsThe screening arm of the Göteborg-1 screening trial comprises 10000 randomly selected men (aged 50–64 yr at randomization) from the Göteborg region of Sweden. Between 1995 and 2014, they were biennially invited to prostate-specific antigen (PSA) testing to an upper age limit of 70 yr (range 67–71 yr). PSA ≥3 ng/ml triggered a prostate biopsy (sextant biopsy 1995–2009, thereafter a ten-core biopsy). Outcome measurements and statistical analysisThe impact of age on Gleason score, given a screen-detected PC, was investigated with multinomial logistic regression analyses adjusted for year of testing and screening round. Results and limitationsOverall, 7625 men had at least one PSA test and 1022 men were diagnosed with PC. For men with screen-detected PC, age was associated with the risk of clinically significant PC above and beyond screening round and year of testing (p < 0.001). For each 1-yr increase in age, the risk of being diagnosed with a Gleason score ≥3 + 4 cancer (vs <7) increased by 11% (95% confidence interval [CI] 4.7–17), whereas the risk of being diagnosed with a Gleason score ≥4 + 3 cancer (vs <7) increased by 8.5% (95% CI –1.6 to 20). ConclusionsThe increased risk of a higher Gleason score in older men should be considered when counseling men regarding early diagnosis and treatment for PC. Patient summaryWe found that older age increased both the risk of prostate cancer and the risk of more aggressive prostate cancer.

Association of Left Atrial Size Measured by Non-Contrast Computed Tomography with Cardiovascular Risk Factors-The Danish Cardiovascular Screening Trial (DANCAVAS).

Left atrium (LA) size is associated with adverse cardiovascular events. The purpose of this study was to investigate the association of LA enlargement measured by non-contrast CT (NCCT) with traditional cardiovascular risk factors. Individuals aged 60–75 years from the population-based multicentre Danish Cardiovascular Screening (DANCAVAS) trial were included in this cross-sectional study. The LA was manually traced on the NCCT scans, and the largest cross-section area was indexed to body surface area. All traditional risk factors were recorded, and a subgroup received an echocardiographic examination. We enrolled 14,987 individuals. Participants with known cardiovascular disease or lacking measurements of LA size or body surface area were excluded, resulting in 10,902 men for the main analysis and 616 women for a sensitivity analysis. Adjusted multivariable analysis showed a significantly increased indexed LA size by increasing age and pulse pressure, while smoking, HbA1c, and total cholesterol were associated with decreased indexed LA size. The findings were confirmed in a supplementary analysis including left ventricle ejection fraction and mass. In this population-based cohort of elderly men, an association was found between age and pulse pressure and increasing LA size. Surprisingly, smoking, HbA1c, and total cholesterol were associated with a decrease in LA size. This indicates that the pathophysiology behind atrial cardiomyopathy is not only reflected by enlargement, but also shrinking.

Population-based randomized trial of screening for clinically significant prostate cancer ProScreen: a pilot study.

ObjectivesTo evaluate the feasibility of a population‐based screening trial using prostate‐specific antigen (PSA), a kallikrein panel and multiparametric magnetic resonance imaging (MRI) aimed at minimizing overdiagnosis, while retaining mortality benefit.Patients and MethodsFeasibility of the screening algorithm was evaluated in terms of participation, screening test results and cancer detection. A random sample of 400 men aged 65 years was identified from the population registry and invited for screening with three stepwise tests (PSA, kallikrein panel and MRI). Men with PSA levels ≥3 ng/mL were further tested with the kallikrein panel, and those with positive findings (risk >7.5%) were referred for prostate MRI. Men with positive MRI (Prostate Imaging Reporting and Data System [PI‐RADS] score 3–5) had targeted biopsies only. Men with negative MRI, but PSA density ≥0.15 underwent systematic biopsies.ResultsOf the 399 men invited, 158 (40%) participated and 27 had PSA levels ≥3 ng/mL (7% of the invited and 17% of the participants). Of these, 22 had a positive kallikrein panel (6% of the invited and 81% of the PSA‐positive men). Finally, 10 men (3% of the invited and 45% of 4Kscore [kallikrein panel]‐positive) had a suspicious MRI finding (PI‐RADS score ≥3) and five were diagnosed with a clinically significant prostate cancer (Gleason Grade Group [GG] ≥2) at fusion biopsy (3% of the participants), with two GG 1 cases (1%). Additional testing (kallikrein panel and MRI) after PSA reduced biopsies by 56%.ConclusionThe findings constitute proof of principle for our screening protocol, as we achieved a substantial detection rate for clinically significant cancer with few clinically insignificant cases. Participation, however, was suboptimal.

PD13-04 PROSTATE CANCER SPECIFIC MORTALITY IN THE ERSPC TRIAL: WHAT IS THE ROLE OF SCREENING RESULT AND ADHERENCE

PD13-04 PROSTATE CANCER SPECIFIC MORTALITY IN THE ERSPC TRIAL: WHAT IS THE ROLE OF SCREENING RESULT AND ADHERENCE

Interobserver reproducibility of perineural invasion of prostatic adenocarcinoma in needle biopsies

Numerous studies have shown a correlation between perineural invasion (PNI) in prostate biopsies and outcome. The reporting of PNI varies widely in the literature. While the interobserver variability of prostate cancer grading has been studied extensively, less is known regarding the reproducibility of PNI. A total of 212 biopsy cores from a population-based screening trial were included in this study (106 with and 106 without PNI according to the original pathology reports). The glass slides were scanned and circulated among four pathologists with a special interest in urological pathology for assessment of PNI. Discordant cases were stained by immunohistochemistry for S-100 protein. PNI was diagnosed by all four observers in 34.0% of cases, while 41.5% were considered to be negative for PNI. In 24.5% of cases, there was a disagreement between the observers. The kappa for interobserver variability was 0.67–0.75 (mean 0.73). The observations from one participant were compared with data from the original reports, and a kappa for intraobserver variability of 0.87 was achieved. Based on immunohistochemical findings among discordant cases, 88.6% had PNI while 11.4% did not. The most common diagnostic pitfall was the presence of bundles of stroma or smooth muscle. It was noted in a few cases that collagenous micronodules could be mistaken for a nerve. The distance between cancer and nerve was another cause of disagreement. Although the results suggest that the reproducibility of PNI may be greater than that of prostate cancer grading, there is still a need for improvement and standardization.

Divergent detection rates of fecal immunochemical test and questionnaire-based risk assessment for detecting proximal and distal advanced colorectal adenomas

Divergent detection rates of fecal immunochemical test and questionnaire-based risk assessment for detecting proximal and distal advanced colorectal adenomas

Efficacy of screening using annual fecal immunochemical test alone versus combined with one-time colonoscopy in reducing colorectal cancer mortality: the Akita Japan population-based colonoscopy screening trial (Akita pop-colon trial)

PurposeScreening programs using fecal occult blood testing help reduce mortality from colorectal cancer (CRC). Colonoscopy and colonoscopy combined with fecal occult blood testing are considered alternatives with higher sensitivity than fecal tests; however, to our knowledge, randomized controlled trials (RCTs) providing such evidence have not been reported. Therefore, this study aimed to compare screening using the fecal immunochemical test (FIT) combined with colonoscopy and FIT alone to evaluate the efficacy of colonoscopy screening in reducing CRC mortality.MethodsThis multicenter, prospective, randomized, controlled study included average-risk individuals for CRC living in the study areas and aged 40–74 years. The exclusion criteria were history of CRC, hereditary non-polyposis CRC, familial adenomatous polyposis, inflammatory bowel diseases, history of cancer other than CRC within the past 5 years, and not expected to survive from comorbid illness. The intervention group underwent one-time colonoscopy and annual FIT, while the control group underwent annual FIT. The primary endpoint was mortality from CRC, while the secondary endpoints were cumulative incidence of invasive CRC, advanced CRC (invasion into the muscle layer or deeper), invasive cancer and screening sensitivities and specificities of invasive CRC, whole CRC, advanced neoplasia, and prevalence of adverse events. The intervention and control groups comprised 4876 and 4875 participants, respectively.ConclusionThis explanatory RCT evaluated the efficacy of colonoscopy screening by valid statistical inference based on randomization. Data on adverse events from this kind of screening are necessary when considering implementation of future screening programs.Trial registrationUMIN Clinical Trials Registry, number UMIN000001980.

Risk or Benefit in Screening for Cardiovascular Disease (ROBINSCA): The Rationale and Study Design of a Population-Based Randomized-Controlled Screening Trial for Cardiovascular Disease

Objectives: This article aims to describe the rationale, study design, and the recruitment process of the Dutch Risk or Benefit in Screening for Cardiovascular Disease (ROBINSCA) trial, worldwide the first population-based randomized-controlled Computed-Tomography (CT) screening trial for cardiovascular disease, powered to detect a benefit of 15% reduced Coronary Heart Disease (CHD) morbidity and mortality. Methods: Addresses of men (aged 45-74 years) and women (aged 55-74 years) were obtained (n=394,058) from the national population registry. All received a mailing with an information brochure, a questionnaire and waist measurement tape and an informed consent form. Asymptomatic people with an expected high-risk for developing CHD were included in this study: 1) a waist circumference of ≥ 102 cm (men) or ≥ 88 cm (women), 2) Body Mass Index of ≥ 30 kg/m2, 3) current smoker and/or 4) a family history of CHD. Eligible respondents were Randomized (1:1:1) to one of the study arms: intervention arm A (screening traditional risk factors), intervention arm B (screening by Coronary Artery Calcium scoring only) or the control arm (usual care). Screened participants with a high risk for developing CHD were referred to the general practitioner for cardiovascular risk management. Linkages with national registries will be performed to measure (CHD-related) morbidity and mortality. Results: A total of 87,866 (22.3%) people responded to the questionnaire, of which 43,447 (49.4%) were Randomized to intervention arm A (n=14,478 (33.3%)), intervention arm B (n=14,450 (33.3%)), or the control arm (n=14,519 (33.4%)). Of those who were considered to be ineligible, one had prior diagnosis of CHD (n=14,156), a medication for hypercholesterolemia and hypertension (n=13,670), no completed informed consent (n=4,490), previous cardiovascular surgery (n=4,146), and/or a CAC score within the last 12 months (n=393). Conclusion: Evidence for net-effectiveness of population-based screening for cardiovascular risk in an asymptomatic population will possibly enable large-scale implementation with large health gains.

Familial Abdominal Aortic Aneurysms Don't Occur Earlier in Life, Neither do they Progress More Rapidly – Observations from Two Population Based Screening Trials

Introduction: Familial Abdominal Aortic Aneurysm (fAAA) is believed to develop earlier in life and progress faster than non-fAAAs. Consequently, current European guidelines recommend screening of first degree relatives to AAA patients from the age of 50. But this recommendation is based on only a few small sized studies. The objective of this study was to compare patient age and size of AAA at diagnosis, and progression of fAAA versus non-fAAAs in two large population-based screening trials. Methods: Study design: Combined population-based cross-sectional and cohort study. Materials: 1099 male participants screened positive for AAA in the VIVA- and DANCAVAS trials. Of these, follow-up data regarding growth rate, the need for aneurysmal repair and death were available in the 617 cases found through the VIVA-study. Using two nationwide registers, the national patient register registering diagnosis and performed procedures, the cause of death register registering causes of death. Ultrasound- and CT-scans were used to determine the maximum abdominal aortic diameter. Data regarding family history, traditional risk factors, prior CVD and medication were obtained by questionnaire at baseline. Difference between the two groups were tested using Wilcoxons ranksum test. Multiple linear regression and multiple cox-regression were used to adjust for potential confounding from age, comorbidities and medication. Finally, using the National Patient Register and Cause of Death register, we investigated the number of patients nationwide diagnosed with a ruptured AAA in different age groups between 1996 and 2016. Results: Of the 1099 AAAs, 77 (7.0%) were fAAAs. We observed no significant difference in age between the two groups, mean age being 70.2 and 69.9 years in the fAAA group and the non-fAAA group, respectively (p=0.99). We did not find any significant difference in median size of the aneurysms (fAAA=38.6 mm versus non-fAAA=36.4 mm. p=0.48). No significant difference was found in the growth rate of the aneurysms (adj. coef. -0.26 cm/y. 95% CI: -1.2 to 0.69), nor in the need for aneurysmal repair (adj. HR=1.10 95% CI: 0.67-1.78) or mortality (Adj. HR=0.43. 95 % CI: 0.16-1.19). Using data from the national patient register and cause of death register we found that 3.9 % percent of aneurysms ruptured before the age of 60 years old and 10.5 % before the age of 65 years. Conclusion: In two large population-based screening trials we found no evidence corroborating the hypothesis that fAAAs develop earlier in life or shows a more aggressive disease progression than non-fAAAs. This questions the current guidelines of screening relatives to AAA patients from a much earlier age than the rest of the population. Disclosure: Nothing to disclose