Degree Of Overdiagnosis Research Articles

Overdiagnosis Due to Screening Mammography for Breast Cancer among Women Aged 40 Years and Over: A Systematic Review and Meta-Analysis

The current systematic review and meta-analysis was conducted to estimate the incidence of overdiagnosis due to screening mammography for breast cancer among women aged 40 years and older. A PRISMA systematic search appraisal and meta-analysis were conducted. A systematic literature search of English publications in PubMed, Web of Science, EMBASE, Scopus, and Google Scholar was conducted without regard to the region or time period. Generic, methodological, and statistical data were extracted from the eligible studies. A meta-analysis was completed by utilizing comprehensive meta-analysis software. The effect size estimates were calculated using the fail-safe N test. The funnel plot and the Begg and Mazumdar rank correlation tests were employed to find any potential bias among the included articles. The strength of the association between two variables was assessed using Kendall's tau. Heterogeneity was measured using the I-squared (I2) test. The literature search in the five databases yielded a total of 4214 studies. Of those, 30 articles were included in the final analysis, with sample sizes ranging from 451 to 1,429,890 women. The vast majority of the articles were retrospective cohort designs (24 articles). The age of the recruited women ranged between 40 and 89 years old. The incidence of overdiagnosis due to screening mammography for breast cancer among women aged 40 years and older was 12.6%. There was high heterogeneity among the study articles (I2 = 99.993), and the pooled event rate was 0.126 (95% CI: 15 0.101-0.156). Despite the random-effects meta-analysis showing a high degree of heterogeneity among the articles, the screening tests have to allow for a certain degree of overdiagnosis (12.6%) due to screening mammography for breast cancer among women aged 40 years and older. Furthermore, efforts should be directed toward controlling and minimizing the harmful consequences associated with breast cancer screening.

Stage-specific incidence trends of melanoma in an English region, 1996-2015: longitudinal analyses of population-based data.

The aim of this study was to examine temporal trends in overall and stage-specific incidence of melanoma. Using population-based data on patients diagnosed with melanoma in East Anglia, England, 1996-2015, we estimated age-standardized time trends in annual incidence rates for each stage at diagnosis. Negative binomial regression was used to model trends over time adjusted for sex, age group and deprivation, and to subsequently examine variation in stage-specific trends by sex and age group. The age-standardized incidence increased from 14 to 29 cases/100 000 persons (i.e. 4% annually). Increasing incidence was apparent across all stages but was steepest for stage I [adjusted annual increase: 5%, 95% confidence interval (CI): 5-6%, and more gradual for stage II-IV disease (stage II: 3%, 95% CI: 2-4%; stage III/IV: 2%, 95% CI: 1-3%)]. Stage II-IV increase was apparent in men across age groups and in women aged 50 years or older. Increases in incidence were steeper in those aged 70 years or older, and in men. The findings suggest that both a genuine increase in the incidence of consequential illness and a degree of overdiagnosis may be responsible for the observed increasing incidence trends in melanoma in our population during the study period. They also suggest the potentially lower effectiveness of public health awareness campaigns in men and older people.

Overdiagnosis of lung cancer with low-dose computed tomography screening: meta-analysis of the randomised clinical trials.

In low-dose computed tomography (LDCT) screening for lung cancer, all three main conditions for overdiagnosis in cancer screening are present: 1) a reservoir of slowly or nongrowing lung cancer exists; 2) LDCT is a high-resolution imaging technology with the potential to identify this reservoir; and 3) eligible screening participants have a high risk of dying from causes other than lung cancer. The degree of overdiagnosis in cancer screening is most validly estimated in high-quality randomised controlled trials (RCTs), with enough follow-up time after the end of screening to avoid lead-time bias and without contamination of the control group.Nine RCTs investigating LDCT screening were identified. Two RCTs were excluded because lung cancer incidence after the end of screening was not published. Two other RCTs using active comparators were also excluded. Therefore, five RCTs were included: two trials were at low risk of bias, two of some concern and one at high risk of bias. In a meta-analysis of the two low risk of bias RCTs including 8156 healthy current or former smokers, 49% of the screen-detected cancers were overdiagnosed. There is uncertainty about this substantial degree of overdiagnosis due to unexplained heterogeneity and low precision of the summed estimate across the two trials.Key pointsNine randomised controlled trials (RCTs) on low-dose computed tomography screening were identified; five were included for meta-analysis but only two of those were at low risk of bias.In a meta-analysis of recent low risk of bias RCTs including 8156 healthy current or former smokers from developed countries, we found that 49% of the screen-detected cancers may be overdiagnosed.There is uncertainty about the degree of overdiagnosis in lung cancer screening due to unexplained heterogeneity and low precision of the point estimate.If only high-quality RCTs are included in the meta-analysis, the degree of overdiagnosis is substantial.Educational aimsTo appreciate that low-dose computed tomography screening for lung cancer meets all three main conditions for overdiagnosis in cancer screening: a reservoir of indolent cancers exists in the population; the screening test is able to “tap” this reservoir by detecting biologically indolent cancers as well as biologically important cancers; and the population being screened is characterised by a relatively high competing risk of death from other causesTo learn about biases that might affect the estimates of overdiagnosis in randomised controlled trials in cancer screening

What has changed in the epidemiology of skin melanoma in central Italy during the past 20 years?

The aim was to evaluate changes in skin melanoma incidence and mortality at a population level in central Italy over the past two decades. Skin melanoma incidence rate from 1994 to 2014, were retrieved from the Umbrian Cancer Registry (about 900 000 inhabitants). Changes from 1994-1999 to 2010-2014 in tumour and patient characteristics - sex, age (0-44, 45-64, ≥ 65 years), site (head and neck, trunk, limbs), morphology (superficial spreading, nodular, other), thickness (≤ 1, 1-2, 2-4, > 4) and stage I-II, III-IV - were evaluated. Trends in age-standardized incidence and mortality rates were evaluated as annual percent change. During the past two decades, melanoma incidence significantly increased in both sexes (+6%/year among men and +4%/year among women) and in all ages (0-44 years: + 4.7 and + 4.3; 45-64 years: + 6.1 and + 4.4; ≥65 years: + 6.6 and + 1.7), morphologies, except nodular, and stages. Mortality was stable among men and women. In the area, incidence increased for thin and thick melanoma, showing a true increase, whereas mortality did not increase. Therefore, although improvements in treatment and downstaging effect of early diagnosis have to be considered, a certain degree of overdiagnosis cannot be ruled out.

Breast cancer biology varies by method of detection and may contribute to overdiagnosis

Recently, it has been suggested that screening mammography may result in some degree of overdiagnosis (ie, detection of breast cancers that would never become clinically important within the lifespan of the patient). The extent and biology of these overdiagnosed cancers, however, is not well understood, and the effect of newer screening modalities on overdiagnosis is unknown. We performed a retrospective review of a prospectively collected database of breast cancers diagnosed at the Yale Breast Center from 2004-2014. The mode of initial presentation was categorized into 5 groups: screening mammogram, screening magnetic resonance imaging, screening ultrasonography, self-detected masses, and physician-detected masses. Compared with cancers presenting with masses, cancers detected by image-based screening were more likely to present with ductal carcinoma-in-situ or T1 cancers (P<.001). In addition to a simple stage shift, however, cancers detected by image-based screening were also more likely to be luminal and low-grade cancers; symptomatic cancers were more likely high-grade and triple-negative (P<.001, respectively). On a multivariate analysis, adjusting for age, race, and tumor size, cancers detected by mammogram, US, and magnetic resonance imaging had greater odds of being luminal (odds ratio 1.8, 95% confidence interval, 1.5-2.3; odds ratio 2.2, 95% confidence interval, 1.1-4.7; and odds ratio4.7, 95% confidence interval, 2.1-10.6, respectively), and low-grade (odds ratio 2.2, 95% confidence interval, 1.6-2.9; odds ratio 4.9, 95% confidence interval, 2.7-8.9; and odds ratio 4.6, 95% confidence interval, 2.6-8.1, respectively) compared with cancers presenting with self-detected masses. Screening detects cancers with more indolent biology, potentially contributing to the observed rate of overdiagnosis. With magnetic resonance imaging and US being used more commonly for screening, the rate of overdiagnosis may increase further.

Treatment and outcomes from a large, prospective, national longitudinal cohort study of screen detected ductal carcinoma in situ (DCIS).

1570Background: The degree of over-diagnosis and over-treatment for ductal carcinoma in situ (DCIS) remains contentious. Hypotheses from retrospective data were tested in a prospective, population-based study. Methods: A prospective longitudinal cohort of 12,838 women diagnosed through a population-based national breast screening program accrued 2003-2012 with proforma for imaging, surgery, pathology and adjuvant therapy. Follow-up was linked to national databases and case note review to analyse patterns of care, recurrence and mortality. Results: Data was complete for 9,972/12,838 (78%) women (mean age 60 years; range 46-87) with median follow up 62 months (range 6-116). Breast conservation (BCS) was definitive surgery for 7,028 (70.5%) women; use increased with older age (CHI2 380, 6 df p < 0.001). Mastectomy (Mx; n = 2,944) was associated with higher grade DCIS (CHI2 19.31, 2 df P < 0.001), larger size (CHI2 203.9, 5 df P < 0.001) and comedo necrosis (CHI2 9.1, 1 df P = 0.003). For patients undergoing ...

CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT

BackgroundThe effects of low-dose CT screening on disease stage shift, mortality and overdiagnosis are unclear. Lung cancer findings and mortality rates are reported at the end of screening in the...

Interval Cancers in Breast Cancer Screening: Comparison of Stage and Biological Characteristics with Screen-Detected Cancers or Incident Cancers in the Absence of Screening

To analyze stage distribution and biological features of interval cancers observed in Verona mammography screening compared to screen-detected cancers and "clinical" cancers occurring in the absence of screening, as provided by the Veneto Cancer Registry. Screen-detected cancers were identified in the screening archives. Interval cancers and clinical cancers (occurring in women never screened or not yet invited) were identified through the local cancer registry. Studied variables were age, stage, pathological pT and pN category, histological grading, estrogen and progesterone receptor status, and proliferation index (Ki67). We compared 95 interval cancers, 761 screen-detected cancers, and 1873 clinical cancer cases. Interval cancers had more aggressive features than screen-detected cancers, the difference being statistically significant for pT (P=106), pN (P = 0.0003), grading (P = 0.007), estrogen receptors (P = 0.0006), and progesterone receptors (P = 0.00005), but not for Ki67 (P = 0.18). The features of interval cancers were not more aggressive than those of clinical cancers for pT (P = 0.84), pN (P = 0.33), grading (P = 0.61), estrogen receptors (P = 0.48), and progesterone receptors (P = 0.69), and were better for Ki67 (P = 0.02). In contrast, screen-detected cancers showed significantly better features than clinical cancers, for all studied variables: pT (P = 10(-6)), pN (P = 10(-6)), grading (P = 10(-6)), estrogen receptors (P = 10(-5)), progesterone receptors (P = 10(-6)), and Ki67 (P = 10(-6)). Our findings are consistent with the length biased sampling hypothesis of interval cancers having a faster growth rate and a less favorable presentation than screen-detected cancers. Compared to clinical cancers, interval cancers had similar features, whereas screen-detected cancers had definitely more favorable features. This finding suggests, rather than a faster growth rate for interval cancers, a slower growth rate for screen-detected cancers, which, together with diagnostic anticipation, may explain a certain degree of overdiagnosis.

Is breast cancer overdiagnosed?

Jørgensen and Gøtzsche quantified the degree of overdiagnosis of breast cancer in five publicly organized mammography screening programs in different parts of the world. overall, they estimated a total degree of breast cancer (including carcinoma in situ) overdiagnosis of 52%, while overdiagnosis for invasive breast cancer was 35%, a finding with potential implications for both clinical practice and public health.

Prostate Cancer Mortality Reduction by Prostate-Specific Antigen–Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC)

Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162,243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening.

Recurrence of gestational diabetes

The recurrence rate of gestational diabetes in 58 patients who had had the foregoing pregnancy complicated by diabetes was estimated to be 30% if our former criteria for abnormal glucose tolerance were strictly applied and 25% if our new, more stringent criteria were used. The recurrence rate is not influenced by prophylactic administration of pyridoxine. The perinatal morbidity complicating the ‘second’ pregnancy of former gestational diabetics was not increased in those patients who were not treated again, as compared with those who were. Recurrent gestational diabetes is associated with a degree of overdiagnosis in an attempt to detect all gestational diabetics. It is suggested that recurrent gestational diabetes occurs mainly in prediabetic patients.