Screen-detected Cases Research Articles

Behaviour and characteristics of low‐grade ductal carcinoma in situ of the breast: literature review and single‐centre retrospective series

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous disease that has risen to prominence and more recently controversy, with the advent of screening mammography. Debate concerning the true biological potential of low nuclear grade DCIS continues to challenge therapeutic considerations. In this study, we carried out a comprehensive literature review of the behaviour, outcomes and current management trials of low-grade DCIS, as well as a retrospective study of a large single institutional series of low-grade DCIS diagnosed at our hospital. The study cohort comprised 195 cases of low-grade DCIS diagnosed at the Singapore General Hospital from 1994 to 2010. Clinicopathological parameters and follow-up data were retrieved and compared between screen-detected and symptomatic low-grade DCIS. Immunohistochemistry was performed for ER, PR and HER2. Among 195 cases, 123 (63.1%) were screen-detected, while 72 (36.9%) were symptomatic. Screen-detected cases had frequent calcifications (P < 0.001) and were smaller (P = 0.018) than symptomatic cases. All cases were ER-positive and rate of PR expression was high. No HER2 overexpression was observed. Mean and median follow-up periods were 107.8 and 109.6 months, respectively. Six patients recurred ipsilaterally, and one patient developed direct distant metastasis. One breast cancer-related death was recorded. Positive surgical margins (P = 0.023) were significantly associated with a higher risk of ipsilateral recurrences, as well as poorer disease-free survivals (P = 0.010). Our data indicate that low-grade DCIS may be followed by invasive recurrences and even metastatic disease, requiring more study before being regarded as innocuous and indolent.

The mammography screening detection of ductal carcinoma in situ and invasive breast cancer according to women's characteristics: is it the same?

Detection of ductal carcinoma in situ (DCIS) has increased with the mammography dissemination. Given the potential role of DCIS as a precursor of invasive breast cancer (IBC), we aimed to assess whether women's characteristics have a different effect on the DCIS compared to IBC detection rate. This study included 3,609,569 screening mammograms performed from 2002 to 2015 in our organized breast cancer screening program, which actively invites women 50-69years of age. The association between women's characteristics and the DCIS detection rate, the IBC detection rate and the odds ratio of DCIS among screen-detected cancers was assessed by logistic regression and generalized estimating equations with independent correlation matrix and sandwich estimator. A total of 4173 DCIS and 15,136 IBC were screen-detected. Increasing women's age, current hormone replacement therapy use and higher body mass index were less associated with the DCIS than with IBC detection rates (p value for the odds of DCIS among screen-detected cancers of, respectively, < 0.0001, 0.0244 and < 0.0001). In contrast, having a previous breast aspiration or biopsy and increasing breast density were more strongly associated with DCIS than with IBC detection rates (p value of, respectively, 0.0050 and < 0.0001). The results suggest that some women's characteristics could be playing a role in the initiation and other in the progression from in situ to invasive breast cancer. These characteristics can also affect the screening sensitivity, and this effect may differ depending on whether screen-detected cases were DCIS or IBC.

Editorial: Doctor's Dilemma or Patient's Choice?

Introduction: It has been estimated that about 50% of screen-detected cases might be over-diagnosed and over-treated. In this paper we analysed the mortality of patients with screen detected cancers in the TARGIT-A trial in which patients >=45 years with an invasive duct carcinoma <=3.5 cm in size and suitable for breast conserving therapy were randomly allocated to receive either risk-adapted TARGIT IORT or conventional course of several weeks of fractionated external beam radiotherapy (EBRT). Method: This was a post-hoc subgroup analysis limited to patients whose cancers were detected by screening mammography, and we compared breast cancer mortality, non-breast cancer mortality and overall mortality between TARGIT and EBRT with Kaplan Meier plots and logrank test. The allocation of cause of death was performed by an independent clinician who was blinded to the randomisation arms of the trial. Results: A total of 3451 patients were recruited into the TARGIT-A trial. Of these, there were 2102 patients whose cancers were diagnosed by mammographic screening (61% of the total). There were 30 deaths recorded: TARGIT 10/1060vs EBRT 20/1042): 7 from breast cancer (TARGIT 4 vs. EBRT 3), 23 from other causes (TARGIT 6, EBRT 17). The overall survival with TARGIT was 2% higher than with EBRT (5-year rates: 98.03% 95%CI 95.97 – 99.04, vs 96.03% 95%CI 93.41 – 97.62, Logrank p = 0.0522), with a doubling of mortality from 2% to 4% in this population. The breast cancer-specific survival was identical between the groups (99%). The difference in overall survival was due to higher non-breast-cancer survival in the TARGIT arm (TARGIT 99.2% and EBRT 96.7%) attributable to deaths in the EBRT arm from cardiac causes and other cancers (TARGIT 3 vs. EBRT 14). Interpretation: Harm from overtreatment of patients with screen detected cancers eligible to receive TARGIT IORT (<3.5 cm ductal cancers), who form a large proportion of the eligible group, in the form of deaths due cardiac causes and other cancers could be potentially avoided if they were instead treated by receive TARGIT IORT instead of conventional external beam radiotherapy. After discussions and volunteers with personal case histories to relate and a break there was a final session to consider the ethical and legal responsibility of doctors in the new era of shared decision-making with a brief run-through of key cases by Suzanne White of Leigh Day solicitors and then a keen Q&A discussion. Should we try for a Judicial Review of the failure to provide IORT in the NHS? Should a case be brought under the Human Rights Act using crowd funding? Something must be done if the medical establishment does not put IORT into practice in the NHS round the country.

Overdiagnosis in the population-based organized breast cancer screening program estimated by a non-homogeneous multi-state model: a cohort study using individual data with long-term follow-up

BackgroundOverdiagnosis, defined as the detection of a cancer that would not become clinically apparent in a woman’s lifetime without screening, has become a growing concern. Similar underlying risk of breast cancer in the screened and control groups is a prerequisite for unbiased estimates of overdiagnosis, but a contemporary control group is usually not available in organized screening programs.MethodsWe estimated the frequency of overdiagnosis of breast cancer due to screening in women 50–69 years old by using individual screening data from the population-based organized screening program in Stockholm County 1989–2014. A hidden Markov model with four latent states and three observed states was constructed to estimate the natural progression of breast cancer and the test sensitivity. Piecewise transition rates were used to consider the time-varying transition rates. The expected number of detected non-progressive breast cancer cases was calculated.ResultsDuring the study period, 2,333,153 invitations were sent out; on average, the participation rate in the screening program was 72.7% and the average recall rate was 2.48%. In total, 14,648 invasive breast cancer cases were diagnosed; among the 8305 screen-detected cases, the expected number of non-progressive breast cancer cases was 35.9, which is equivalent to 0.43% (95% confidence interval (CI) 0.10%–2.2%) overdiagnosis. The corresponding estimates for the prevalent and subsequent rounds were 15.6 (0.87%, 95% CI 0.20%–4.3%) and 20.3 (0.31%, 95% CI 0.07%–1.6%), respectively. The likelihood ratio test showed that the non-homogeneous model fitted the data better than an age-homogeneous model (P <0.001).ConclusionsOur findings suggest that overdiagnosis in the organized biennial mammographic screening for women 50–69 in Stockholm County is a minor phenomenon. The frequency of overdiagnosis in the prevalent screening round was higher than that in subsequent rounds. The non-homogeneous model performed better than the simpler, traditional homogeneous model.

Diagnostic routes and time intervals for patients with colorectal cancer in 10 international jurisdictions; findings from a cross-sectional study from the International Cancer Benchmarking Partnership (ICBP)

ObjectiveInternational differences in colorectal cancer (CRC) survival and stage at diagnosis have been reported previously. They may be linked to differences in time intervals and routes to diagnosis. The International...

Long-Term Breast Cancer Survival Affected by Overdiagnosis

Background: Overdetected breast cancers (BCs) via mammography screening that are biologically nonprogressive and unnecessary to receive treatment is of great concern for population-based screening. Most previous studies estimated overdiagnosis by excess incidence due to the introduction of screening compared with background incidence derived from randomized control trial, which require population incident-based BC data and the strong assumption of lead-time distribution, few studies have been adopted by using merely follow-up data on BCs. Aim: To assess respective independent contributions of overdiagnosis and curation to long-term breast cancer survival by the application of the novel zero-inflated statistical model to a longitudinal follow up empirical data with sufficient information based on patient-based data. Methods: We designed a retrospective cohort composed of 1346 patients diagnosed with invasive breast cancer in Falun Central Hospital of Dalarna County, Sweden, through international collaboration. A novel zero-inflated cured or overdiagnosis regression model was conducted. The zero part represents both types of nonprogressive cancer without potential of dying from BC, the cured due to treatment and the overdiagnosed due to mammography screening. These 2 types would be distinguished by detection modes (screen-detected cases and interval cancer plus cancers from nonparticipants). The count part represents the progressive breast cancer with potential of dying from BC associated with prognostic factors during follow-up. Results: The probability for nonprogressive BC (the zero part) was 56.14%. The probability of zero due to curation resulting from early detection and effective treatment was 44.34%. Overdiagnosis resulting from mammography screening program was 8.94% and high awareness was 2.86%. Among 43.86% progressive BC (the count part), 32.11% patients undergoing subsequent adjuvant therapies still remained alive after 15-year follow-up when adjusting for significant prognostic factors. The 15-year prognosis-adjusted cumulative survival of BC was dropped from 88.25% to 74.80% after correcting for the zero-inflated part of overdiagnosis. Conclusion: The proposed zero-inflated model with 15 years of follow-up data revealed 12% due to overdiagnosis after taking out the probability of zero due to curation as a result of early detection and effective treatment from the total zero part.

Effectiveness of Population-Based Cancer Screening Only Based on Survival Data Considering Latent Lead-Time and Truncation Biases

Background: When evaluating the effectiveness of population-based screening program (comparison of survival between screen-detected and clinically detected cases), latent lead time and truncation are both inherent biases from screen-detected cases. Following the disease natural history, the time spent in preclinical screen-detectable cases (PCDP) called sojourn time is an important factor to determine these 2 biases, lead-time bias and length bias. The first is the time from diagnosis at screen to hypothetical diagnosis (entering clinical phase) depending on the sojourn time should be subtracted from the overall survival time to achieve a fair comparison. The second is pertaining to oversampling cases with long sojourn time at prevalent screen. The survival benefit is often overestimated without considering these 2 biases. Aim: To unbiasedly estimate the effectiveness of population-based screening in terms of hazard ratio between screen-detected and clinically detected cases. Methods: Walter and Stitt (1985) has already proposed a parametric approach to adjust lead-time bias. However, lead-time bias and truncation biases are correlated as both have shared information on sojourn time in common, and therefore we aim to consider these 2 biases at the same time. Both parametric and semiparametric approaches are proposed to address the hazard ratio of risk of cancer death adjusting for lead-time and truncation biases based on data from the Swedish W-county trial. The estimation of parameters computer algorithms was also adopted with non-Bayesian and Bayesian approaches using SAS and R. Results: By using parametric approach, the hazard ratio was inflated from 0.26 (0.18-0.36) without adjustment to 0.38 (0.25-0.55) with lead-time adjustment and 0.43 (0.27-0.60) with both lead-time and truncation adjustments. The use of semiparametric model led to 0.59 (0.49-0.70) of adjusted hazard ratio. After considering tumor attributes, the hazard ratio was inflated to 0.76 (0.45-1.11) and 0.87 (0.71-1.04) separately under parametric and semiparametric approaches. Conclusion: Unbiased evaluation of effectiveness of population-based screen with adjustment for lead-time and truncation biases based on survival data are efficient and feasible.

Rural-Urban Variation in Time to Diagnosis and Treatment of Colorectal or Breast Cancer in Victoria, Australia

Background: Rural-urban disparities in cancer outcomes are found in many countries, though these vary by cancer type. In Victoria, Australia, survival is poorer for rural patients with colorectal cancer, but not breast cancer. Delayed diagnosis and treatment may contribute to disparities, but previous studies have not compared the timeliness of rural and urban pathways to treatment of these common cancers. Aim: We investigated whether time to diagnosis and treatment differed for rural and urban patients with colorectal or breast cancer in Victoria, Australia. Methods: Population-based, cross-sectional surveys examining events and dates on the pathway to treatment completed by patients aged ≥ 40 and approached within six months of diagnosis, their general practitioner (GP) and specialist. Data were collected from 2013 to 2014 as part of the International Cancer Benchmarking Partnership, Module 4. Six intervals were explored: patient (symptom to presentation), primary care (presentation to referral), diagnostic (presentation/screening to diagnosis), treatment (diagnosis to treatment), health system (presentation to treatment) and total intervals (symptom/screening to treatment). Rural-urban differences were examined for each cancer using quantile regression (50th, 75th and 90th percentiles) models including age, gender, health insurance and socioeconomic status. Results: 433 colorectal (48% rural) and 489 breast (42% rural) patients, 621 GPs and 370 specialists completed surveys. Compared with urban patients, symptomatic colorectal cancer patients from rural areas had a significantly longer total interval at all percentiles: 50th (18 days longer, 95% confidence interval (CI): 9-27), 75th (53, 95% CI: 47-59) 90th (44, 95% CI: 40-48). These patients also had longer health system intervals, ranging 7-85 days longer. This appeared mostly due to longer diagnostic intervals (range: 6-54 days longer). Results were similar when including screen-detected cases. In contrast, breast cancer intervals were similar for rural and urban patients, except the patient interval, which was shorter for rural patients. Conclusion: Consistent with variation in survival, we found longer total and diagnostic intervals for rural compared with urban patients with colorectal cancer, but not breast cancer. The lack of rural-urban differences observed for breast cancer suggest that inequities in the timeliness of colorectal cancer pathways can be ameliorated, and may improve clinical outcomes. Indeed, based on previous research, delays observed in this study could result in stage progression and hence reduced survival. From our results, interventions targeting the time from presentation to colorectal cancer diagnosis in rural populations should be pursued. Countries seeking to understand cancer disparities in their local context may also consider using a pathways approach to identify possible targets for policy intervention.

Factors associated with screen-detected breast cancer across five Canadian provinces: a CanIMPACT study

IntroductionBreast cancer screening is intended to identify cancer in early stages when prognosis is better and treatments less invasive.&#x0D; Objectives and ApproachWe describe Canadian inter- and intra-provincial variation in the percentage of screen-detected cases and identify factors related to having a screen-detected versus a non-screen detected breast cancer.&#x0D; Breast cancers diagnosed from 2004/7 to 2010/11/12 in 5 Canadian provinces were included. Standard provincial datasets were created using screening program and claims data. A common algorithm (Alberta, Ontario) or variable from the screening dataset (British Columbia, Manitoba, Nova Scotia) was used to identify the mode of diagnosis (screening versus not). Relationship between screen-detected cancer and several demographic, clinical and healthcare utilization factors were explored.&#x0D; ResultsThe percentage of screen-detected breast cancers varied from 25 to 40 percent across provinces; it ranged 43 to 51 percent for those aged 50-69. Within provinces, the percentage of screen-detected cancers varied across regional health authorities by a low of 1\% to a high of 33\%. Urban residence was positively associated with screen-detection in some provinces and negatively in others. Women in the lowest neighborhood income quintile had the smallest proportion of screen-detected cancers; the absolute difference from those in the highest quintiles ranged from 3.3-11.5\% across provinces. High continuity of care with a usual primary care provider was positively associated with having a screen-detected cancer compared to those with no usual care provider.&#x0D; Conclusion/ImplicationsThe proportion of screen-detected breast cancers varied significantly across and within provinces suggesting geographic variability in access to screening services. Variation across provinces in terms of factors associated with screen-detected breast cancer also likely reflect access issues. The positive association of high continuity of care with screen-detection in all provinces suggests that regular care with a primary care physician is an important factor in improving screening rates and detection.

Lesions of \u201cuncertain malignant potential\u201d in the breast (B3) identified with mammography screening

BackgroundCore needle biopsy (CNB) is a standard diagnostic procedure in the setting of breast cancer screening. However, CNB may result in the borderline diagnoses of lesion of uncertain malignant potential (B3). The aim of this study was to access the outcome of lesions diagnosed as B3 category in a large series of screen-detected cases to evaluate the rates of malignancy for the different histological subtypes.MethodsWe identified all CNBs over a six-year period (2009-2015) in a breast cancer screening unit in Germany. A total of 8.388 CNB’s were performed for screen detected breast lesions. B3 diagnosis comprised 4.5% (376/8.388). Of the 376 patients who were diagnosed as B3, 299 underwent subsequent excision biopsy with final excision histology.ResultsOut of 376 patients diagnosed with B3 lesions, the prevalence of different histopathology showed 161 (42.8%) patients with atypical ductal hyperplasia (ADH), 98 (26.1%) with flat epithelial atypia (FEA), 50 women (13.3%) showed lobular neoplasia (LN), in 40 (10.6%) patients papillary findings and in 27 patients (7.2%) a radial scar complex. Final excision histology was benign in 74% (221/299) and malignant in 26% (78/299) of the patients. Lesion specific positive predictive values (PPV) for a subsequent diagnosis of in situ or invasive carcinoma were as follows: ADH 40%, FEA 20.5%, papillary lesion 13.5%, radial scar 16.6%, LN 0%.ConclusionOur results show that approximately one-third of core needle biopsies of screen detected breast lesions classified as B3 are premalignant or malignant on excision.Lesions of uncertain malignant potential of the breast (B3) are heterogeneous in respect to risk of malignancy.

Reducing harms from treatment. Sixteen years of surgery of the axilla for screen-detected breast cancers in Italy

ObjectivesAvailable evidence on axillary surgery has accumulated dramatically in the last two decades in favor of less invasive care. The aim of this paper is to study 16-years trends in the surgical management of the axilla in a large population-based data set of screen-detected breast cancers in Italy and to document at what extent recommendations have been adopted in actual clinical care. Material and methodsThis is a retrospective cohort study documenting the surgical management of the axilla in primary breast cancer patients over time. We retrieved from the Italian database of screen-detected cancers 41213 cases diagnosed in women aged 50–69 between years 2000 and 2015 in twelve Italian Regions. ResultsIn pN0 cases, an increasing trend (p < 0.001) in the number of patients who received sentinel lymph node biopsy (SLNB) as the only axillary staging procedure was observed. In pN + cases SLNB was the only staging procedure in an increasing number of patients (p < 0.001) especially since the publication of the ACOSOG-Z0011 paper. In ductal carcinoma in situ (DCIS) SLNB was more frequent in mastectomies and in high grade and large lesions. However, 45% of low grade, small DCIS over the whole time period had some form of axillary surgery. ConclusionThis large series of screen-detected cases documents a strong time trend in the direction of reducing axillary surgery and hence potential harms from treatment. The continuing practice of SLNB in low risk DCIS is of concern in an era of increasing awareness towards overdiagnosis and overtreatment.

Impact of Overdiagnosis on Long-Term Survival of Breast Cancer

Background: While overdiagnosis becomes the main concern in breast cancer screening with mammography its influence on long-term survival of breast cancer is poorly understood and intractably quantified because of indistinguishability between overdiagnosis and curation. We aimed to assess respective independent contributions of overdiagnosis and curation to long-term survival of breast cancer. Methods: We elucidated this thorny issue by using a Swedish Dalarna cohort with long-term follow-up of 1346 invasive breast cancers from 1996 onwards together with a zero (cured or overdiagnosis)-inflated model design and analysis. The zero part represents both types of non-progressive cancer without potential of dying from BC, the cured due to effective treatment and the over-diagnosed due to mammography screening. These two types can be distinguished by the provision of information on detection modes (screen-detected cases and interval cancer plus cancers from non-participants). The count part represents the progressive breast cancer with potential of dying from BC depending on prognostic factors during follow-up. Findings: The probability for non-progressive BC (the zero part) was 56·14% including 44·34% due to the curation after early detection and initial treatment and 11·80% due to overdiagnosis resulting from mammography screening program (8·94%) and high awareness (2·86%). Among 43·86% progressive BC (the count part), 32·11% undergoing subsequent adjuvant therapies still remained alive after 15-years of follow-up when adjusting for significant prognostic factors. The 15-year prognosis-adjusted cumulative survival of BC was dropped from 88·25% to 74·80% after correcting for the zero-inflated part of overdiagnosis. Interpretation. The proposed zero-inflated model design and analysis together with information on detection mode with 15 years of follow-up revealed 76% survivors of BC due to the curation resulting from mammography screening and accompanying effective treatment and therapy and 12% due to overdiagnosis. Funding: HHC, AMFY, SLSC, and CYH are supported by the Ministry of Science and Technology grant (grant number MOST 106-2118-M-002-006-MY2; MOST 106-2118-M-038-002-MY2; MOST 106-2811-M-002-075; MOST 107-3017-F-002-003). HHC is supported by The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan (NTU-107L9003). Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: This study was approved by the Joint Institutional Review Board of Taipei Medical University (TMU-JIRB, approval numbers N201607008).

Screening status, tumour subtype, and breast cancer survival: a national population-based analysis.

We examined whether demographic and tumour characteristics (including subtype) were different for women with breast cancer diagnosed via mammography screening compared with women with interval breast cancers, lapsed attenders of the screening programme and non-participants of the screening programme. In addition, we explored whether there were survival differences between the groups, taking into account lead time bias. We used linked data from National Cancer Registry Ireland and the national breast screening programme BreastCheck. Multinomial logistic regression was used to test the association of covariates with screening status. For survival analysis, we corrected the survival time for screen-detected cases for lead time bias, examined Kaplan-Meier curves and then used Cox regression to investigate differences in survival by screening status. Subtype (HER2 over-expressing, triple negative), stage (III/IV), grade (poor), having co-morbidities, area of deprivation, smoking status and age were associated with having interval cancer or being a non-participant of the screening programme in the multivariable model. After correcting for lead time bias, and adjusting for variables associated with screening status, there was no evidence that risk of breast-cancer death for women with screen-detected cancer was different from women with interval cancer (HR = 0.76, 95% CI 0.56-1.03), non-participants (HR = 1.07, 95% CI 0.84-1.37) and lapsed attenders (HR = 0.97, 95% CI 0.65-1.45). Screening status was strongly associated with subtype and this association persisted after adjustment for covariates including tumour stage and grade. After correcting for lead-time bias and adjusting for stage, subtype, grade and socio-demographic variables, no significant survival difference was demonstrated for women with screen-detected cancer in the 5-year period post-diagnosis. Since we are adjusting for stage, subtype and other variables, the lack of difference between these groups would be expected but has not been demonstrated in studies which do not correct for lead time bias.

Population Screening for T1D and Celiac Disease—Autoimmunity Screening for Kids (ASK)

Early detection can prevent morbidity associated with type 1 diabetes (T1D) and celiac disease (CD). ASK is a 4-year program with the goal to screen Denver metro-area children for pre-symptomatic T1D and CD, increase public awareness of these diseases, and provide evidence for universal screening. We are reporting first-ever prevalence data for pre-symptomatic T1D and CD in the U.S. general population children aged 2-17 y. In 2017, ASK approached ∼15,000 children for consent, screened 5090 with results available for 4915. Study participant age, sex, and race/ethnicity closely reflected Denver’s general population; 4% had a T1D first-degree relative (FDR). Standard radiobinding assays (RBA) and more specific electrochemiluminescence (ECL) assays for autoantibodies to insulin, GAD, IA-2, ZnT8 and transglutaminase (TGA) were used for screening and confirmation. Children with confirmed persistent islet autoantibodies received follow-up with education to prevent DKA, psychological support, and referrals to prevention trials or clinical services. Multiple islet autoantibodies, predicting a 44% 5-y risk of T1D, were found in 32 (0.7%) children; of the 30 children retested to date, all remained persistently positive, six developed dysglycemia and one progressed to T1D. A single islet autoantibody, confirmed as high-affinity by ECL (29% 5-y risk of T1D), was found in 27 (0.5%); 18/19 children retested remained positive, 5 developed dysglycemia and one T1D. Over 86% (50/59) of the screening-detected children at risk for T1D did not have an FDR with T1D. The prevalence of TGA by both RBA and ECL was 2.2% and persistent in 74/76 (97%) children retested so far. This novel population-based screening program for the two most common autoimmune diseases of childhood reports high prevalence of pre-symptomatic T1D and CD in Denver children. Prospective follow-up of screening-detected cases for clinical outcomes and cost-effectiveness analysis will inform potential future universal screening. Disclosure C.R. Geno Rasmussen: None. M. Rewers: None. J. Baxter: None. K. Waugh: None. A. Steck: None. B.I. Frohnert: None. L. Yu: None. E. Liu: None.

Estimation of Lead Time via Low-Dose CT in the National Lung Screening Trial.

Based on recent reports from the National Lung Screening Trial (NLST), smokers who were screened by low-dose computer tomography (LDCT) had a 20% lower chance of dying from lung cancer than those screened by chest X-rays. However, due to the complexities of lead time bias and over diagnosis, no formal test has been shown to reduce lung cancer mortality. To correctly evaluate survival benefit due to early detection, it is critical to estimate lead time, the length of time that detection of a disease is advanced by screening. We applied a recently developed probability method to estimate lead time, using the LDCT data from NLST, where human lifetime was treated as random and derived from the actuarial life table of the US Social Security Administration. Using Bayesian posterior samples of key parameters extracted from the NLST-LDCT data, simulations on lead time were carried out on 16 hypothetical cohorts with four initial ages (55, 60, 65, and 70) and four future screening intervals (12, 18, 24, and 30months). For each scenario, the estimated lead time for both screen-detected and interval cases is reported. Results show that the probability of no-early-detection (interval cases) increases monotonically when the screening interval increases for both genders. A male heavy smoker with an initial screening age at 60 has 11.65% (female 6.76%) chance of no-early-detection with annual screenings. This probability increases to 36.35% (female 28.26%) if the screenings were biennial. The mean lead time appears longer for women than for men. The mean lead time decreases when the screening interval increases, but it appears stable across different initial age groups. These results lay a foundation to evaluate survival benefit accurately with LDCT and to schedule future screening exams.

Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis

BackgroundMammography is less effective in detecting cancer in dense than in fatty breasts.MethodsWe undertook a systematic search in PubMed to identify studies on women with dense breasts who underwent screening with mammography supplemented with ultrasound. A meta-analysis was undertaken on the proportion of cancers detected only by ultrasound, out of all screen-detected cancers, and the proportion of women with negative mammography who were referred for assessment following ultrasound screening.ResultsTwenty-nine studies satisfied our inclusion criteria. The proportion of total cancers detected only by ultrasound was 0.29 (95% CI: 0.27–0.31), consistent with an approximately 40% increase in the detection of cancers compared to mammography. In the studied populations, this translated into an additional 3.8 (95% CI: 3.4–4.2) screen-detected cases per 1000 mammography-negative women. About 13% (32/248) of cancers were in situ from 17 studies with information on this subgroup. Ultrasound approximately doubled the referral for assessment in three studies with these data.ConclusionsStudies have consistently shown an increased detection of breast cancer by supplementary ultrasound screening. An inclusion of supplementary ultrasound into routine screening will need to consider the availability of ultrasound and diagnostic assessment capacities.

Comparison of pathological characteristics between self-detected and screen-detected invasive breast cancers in Chinese women: a retrospective study

BackgroundIn China, there is insufficient evidence to support that screening programs can detect breast cancer earlier and improve outcomes compared with patient self-reporting. Therefore, we compared the pathological characteristics at diagnosis between self-detected and screen-detected cases of invasive breast cancer at our institution and determined whether these characteristics were different after the program’s introduction (vs. prior to).MethodsThree databases were selected (breast cancer diagnosed in 1995–2000, 2010, and 2015), which provided a total of 3,014 female patients with invasive breast cancer. The cases were divided into self-detected and screen-detected groups. The pathological characteristics were compared between the two groups and multiple imputation and complete randomized imputation were used to deal with missing data.ResultsCompared with patient self-reporting, screening was associated with the following factors: a higher percentage of stage T1 tumors (75.0% vs 17.1%, P = 0.109 in 1995–2000; 66.7% vs 40.4%, P < 0.001 in 2010; 67.8% vs 35.7%, P < 0.001 in 2015); a higher percentage of tumors with stage N0 lymph node status (67.3% vs. 48.4%, P = 0.007 in 2010); and a higher percentage of histologic grade I tumors (22.9% vs 13.9%, P = 0.017 in 2010).ConclusionScreen-detected breast cancer was associated with a greater number of favorable pathological characteristics. However, although screening had a beneficial role in early detection in China, we found fewer patients were detected by screening in this study compared with those in Western and Asian developed countries.

Extraintestinal manifestations were common in children with coeliac disease and were more prevalent in patients with more severe clinical and histological presentation.

This study investigated the prevalence of extraintestinal manifestations (EIM) in paediatric coeliac disease and their associations with other disease features. Researchers at the University of Tampere, Finland, compared EIM in 511 children diagnosed with coeliac disease from 2003 to 2014 and 180 diagnosed with functional gastrointestinal disorders from 2007 to 2013. Disease severity and dietary responses were also compared between coeliac children diagnosed by screening (n = 146) or because of EIM (n = 116) or gastrointestinal symptoms (n = 249). Coeliac patients had more EIM (62%) than those with functional disorders (33%). The most common EIM in coeliac children were poor growth (27%) and anaemia (18%). Children with coeliac disease often showed fatigue (8%) and symptoms affecting the skin (15%), nervous system (9%) and joints (6%). Coeliac patients with EIM as their main clinical presentation had more severe symptoms and histological damage at diagnosis than those with gastrointestinal presentation and screen-detected cases. The subgroups did not differ with regard to other clinical and laboratory parameters and dietary adherence. Concomitant EIM were also common in children diagnosed because of gastrointestinal presentation (60%) and by screening (37%). EIM were common in coeliac disease and associated with more severe clinical and histological presentation.

Mental Health Screening, Treatment, and Institutional Incidents: A Propensity Score Matched Analysis of Long-Term Outcomes of Screening

ABSTRACTThere is little study of the impacts of screening on distal outcomes such as recovery or adverse incidents during incarceration. Furthermore, screening practices vary greatly between jurisdictions; many focus on history taking as opposed to current symptoms.Method. We conducted an observational cohort study of all admissions (N = 13,281) to Canadian prisons over a 33-month period. We used full matching on propensity scores to explore the association between treatment and health, violent and victimization incidents.Results. Treatment was associated with lower rates of victimization and violence for all inmates, and health incidents among screen-detected cases. Among inmates with pre-existing risk–who accounted for 90% of health incidents—treatment was associated with increased risk of a first incident but decreased risk of recurrent incidents.Implications. In-depth symptom-based screening identified a group of inmates who benefited from treatment, but accounted for relatively few incidents. Tensions of prioritizing resources for pre-existing vs, incident mental illness were highlighted by weaker treatment effects for those with pre-existing needs. Increased use of diversion options to keep inmates with mental illness out of prisons, and determining the appropriate intensity of intervention to meet the needs of screen-detected cases could alleviate some of these tensions.

Inference of Long-Term Screening Outcomes for Individuals with Screening Histories

ABSTRACTWe develop a probability model for evaluating long-term outcomes due to regular screening that incorporates the effects of prior screening examinations. Previous models assume that individuals have no prior screening examinations at their current ages. Due to current widespread medical emphasis on screening, the consideration of screening histories is essential, particularly in assessing the benefit of future screening examinations given a certain number of previous negative screens. Screening participants are categorized into four mutually exclusive groups: symptom-free-life, no-early-detection, true-early-detection, and overdiagnosis. For each case, we develop models that incorporate a person’s current age, screening history, expected future screening frequency, screening test sensitivity, and other factors, and derive the probabilities of occurrence for the four groups. The probability of overdiagnosis among screen-detected cases is derived and estimated. The model applies to screening for any disease or condition; for concreteness, we focus on female breast cancer and use data from the study conducted by the Health Insurance Plan of Greater New York (HIP) to estimate these probabilities and corresponding credible intervals. The model can provide policy makers with important information regarding ranges of expected lives saved and percentages of true-early-detection and overdiagnosis among the screen-detected cases.