Interval Cancer Rate Research Articles

Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial.

Two dimensional (2D) full-field digital mammography is the current standard of breast cancer screening. Digital breast tomosynthesis generates pseudo-three dimensional datasets of the breast from which synthesised 2D (s2D) mammograms can be reconstructed. This innovative approach reduces the likelihood of overlapping breast tissues that can conceal features of malignancy. We aimed to compare digital breast tomosynthesis plus s2D mammography with digital screening mammography for the detection of invasive breast cancer. TOSYMA was a randomised, open-label, superiority trial done at 17 screening units in two federal states of Germany. Eligible participants were women aged 50-69 years who had been invited to participate in a population-wide, quality-controlled mammography screening programme. Women were randomly assigned (1:1) to digital breast tomosynthesis plus s2D mammography or digital mammography alone using block randomisation (block size of 32), stratified by site. The primary endpoints were the detection rate of invasive breast cancer and invasive interval cancer rate at 24 months, analysed in the modified full analysis set, which included all randomly assigned participants who underwent either type of screening examination. Ten examinations, corresponding to a second study participation, were excluded. Analyses were done according to the intention-to-treat principle. Interval cancer rates will be reported in the follow-up study. Safety was assessed in the as-treated population, which included all participants who were randomly assigned. This trial is registered with ClinicalTrials.gov, NCT03377036, and is closed to accrual. Between July 5, 2018, and Dec 30, 2020, 99 689 women were randomly assigned to digital breast tomosynthesis plus s2D mammography (n=49 804) or digital mammography (n=49 830). Invasive breast cancers were detected in 354 of 49 715 women with evaluable primary endpoint data in the digital breast tomosynthesis plus s2D group (detection rate 7·1 cases per 1000 women screened) and in 240 of 49 762 women in the digital mammography group (4·8 cases per 1000 women screened; odds ratio 1·48 [95% CI 1·25-1·75]; p<0·0001). Adverse events and device deficiencies were rare (six adverse events in each group; 23 device deficiencies in the digital breast tomosynthesis plus s2D group vs five device deficiencies in the digital mammography group) and no serious adverse events were reported. The results from this study indicate that the detection rate for invasive breast cancer was significantly higher with digital breast tomosynthesis plus s2D mammography than digital mammography alone. Evaluation of interval cancer rates in the follow-up study will further help to investigate incremental long-term benefits of digital breast tomosynthesis screening. Deutsche Forschungsgemeinschaft (German Research Foundation).

High-Quality Colonoscopy: A Review of Quality Indicators and Best Practices

Colorectal cancer (CRC) continues to be the third leading cause of cancer-related deaths in the US. Colonoscopy remains the best preventative tool against the development of CRC. As a result, high-quality colonoscopy is becoming increasingly important. Specifically, recent guidelines have highlighted pre-procedural, peri-procedural, and post-procedural practices, which promise to improve patient outcomes and reduce the mortality and interval cancer rates in patients undergoing colonoscopies. Despite the guidelines and advances in modern endoscopy, the procedure remains provider-dependent, which results in differences in outcomes. As a result, incorporating high-quality colonoscopy approaches early in training is key to improving patient outcomes. Additionally, ensuring that high-quality colonoscopy is practiced widely by endoscopists can lead to the most cost-effective care.

Should tomosynthesis replace mammography for breast cancer screening?

A decade has passed since the first prospective trials showed that the mammography technology, digital breast tomosynthesis, increased the rate of cancer detection compared with digital mammography. 1 Ciatto S Houssami N Bernardi D et al. Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study. Lancet Oncol. 2013; 14: 583-589 Summary Full Text Full Text PDF PubMed Scopus (608) Google Scholar , 2 Skaane P Bandos AI Gullien R et al. Prospective trial comparing full-field digital mammography (FFDM) versus combined FFDM and tomosynthesis in a population-based screening programme using independent double reading with arbitration. Eur Radiol. 2013; 23: 2061-2071 Crossref PubMed Scopus (170) Google Scholar A large body of evidence, comprising prospective non-randomised studies and retrospective studies, 3 Marinovich ML Hunter KE Macaskill P Houssami N Breast cancer screening using tomosynthesis or mammography: a meta-analysis of cancer detection and recall. J Natl Cancer Inst. 2018; 110: 942-949 Crossref PubMed Scopus (108) Google Scholar has since accumulated; however, evidence from randomised controlled trials is scarce. In The Lancet Oncology, Walter Heindel and colleagues report the results of the TOmosynthesis plus SYnthesised MAmmography Study (TOSYMA), 4 Heindel W Weigel W Gerß J et al. Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial. Lancet Oncol. 2022; (published online April 12.)https://doi.org/10.1016/S1470-2045(22)00194-2 Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar a multicentre trial embedded in the German population-wide mammography screening programme. TOSYMA is the largest of three randomised controlled trials providing evidence on breast tomosynthesis versus mammography screening. 4 Heindel W Weigel W Gerß J et al. Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial. Lancet Oncol. 2022; (published online April 12.)https://doi.org/10.1016/S1470-2045(22)00194-2 Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar , 5 Hofvind S Holen AS Aase HS et al. Two-view digital breast tomosynthesis versus digital mammography in a population-based breast cancer screening programme (To-Be): a randomised, controlled trial. Lancet Oncol. 2019; 20: 795-805 Summary Full Text Full Text PDF PubMed Scopus (38) Google Scholar , 6 Pattacini P Nitrosi A Giorgi RP et al. A randomized trial comparing breast cancer incidence and interval cancers after tomosynthesis plus mammography versus mammography alone. Radiology. 2022; (published online Feb 1.)https://doi.org/10.1148/radiol.211132 Crossref PubMed Scopus (3) Google Scholar Heindel and colleagues persevered with TOSYMA despite the COVID-19 pandemic stalling recruitment, resulting in a marginally lower sample size than planned in their adaptive design. 4 Heindel W Weigel W Gerß J et al. Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial. Lancet Oncol. 2022; (published online April 12.)https://doi.org/10.1016/S1470-2045(22)00194-2 Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trialThe results from this study indicate that the detection rate for invasive breast cancer was significantly higher with digital breast tomosynthesis plus s2D mammography than digital mammography alone. Evaluation of interval cancer rates in the follow-up study will further help to investigate incremental long-term benefits of digital breast tomosynthesis screening. Full-Text PDF

AI-based prevention of interval cancers in a national mammography screening program

PurposeTo demonstrate that artificial intelligence (AI) can detect and correctly localise retrospectively visible cancers that were missed and diagnosed as interval cancers (false negative (FN) and minimal signs (MS) interval cancers), and to characterise AI performance on non-visible occult and true interval cancers. MethodPrior screening mammograms from N = 2,396 women diagnosed with interval breast cancer between March 2006 and May 2018 in north-western Germany were analysed with an AI system, producing a model score for all studies. All included studies previously underwent independent radiological review at a mammography reference centre to confirm interval cancer classification. Model score distributions were visualised with histograms. We computed the proportion and accompanying 95% confidence intervals (CI) of retrospectively visible and true interval cancers detected and correctly localised by AI at different operating points representing recall rates < 3%. Clinicopathological characteristics of retrospectively visible cancers detected by AI and not were compared using the Chi-squared test and binary logistic regression. ResultsFollowing radiological review, 15.6% of the interval cancer cases were categorised as FN, 19.5% MS, 11.4% occult, and 53.4% true interval cancers. At an operating point of 99.0% specificity, AI could detect and correctly localise 27.5% (95% CI: 23.3–32.3%), and 12.2% (95% CI: 9.5–15.5%) of the FN and MS cases on the prior mammogram, respectively. 228 of these retrospectively visible cases were advanced/metastatic at diagnosis; 21.1% (95% CI: 16.3–26.8%) were found by AI on the screening mammogram. Increased likelihood of detection of retrospectively visible cancers with AI was observed for lower-grade carcinomas and those with involved lymph nodes at diagnosis. Among true interval cancers, AI could detect and correctly localise in the screening mammogram where subsequent malignancies would appear in 2.8% (95% CI: 2.0–3.9%) of cases. ConclusionsAI can support radiologists by detecting a greater number of carcinomas, subsequently decreasing the interval cancer rate and the number of advanced and metastatic cancers.

Early screening outcomes among non-immigrants and immigrants targeted by BreastScreen Norway, 2010-2019.

This study aimed to analyse results on early screening outcomes, including recall and cancer rates, and histopathological tumour characteristics among non-immigrants and immigrants invited to BreastScreen Norway. We included information about 2, 763,230 invitations and 2,087,222 screening examinations from 805,543 women aged 50-69 years who were invited to BreastScreen Norway between 2010 and 2019. Women were stratified into three groups based on their birth country: non-immigrants, immigrants born in Western countries and immigrants born in non-Western countries. Age-adjusted regression models were used to analyse early screening outcomes. A random intercept effect was included in models where women underwent several screening examinations. The overall attendance was 77.5% for non-immigrants, 68% for immigrants from Western countries and 51.5% for immigrants from non-Western countries. The rate of screen-detected cancers was 5.9/1000 screening examinations for non-immigrants, 6.3/1000 for immigrants from Western countries and 5.1/1000 for immigrants from non-Western countries. Adjusted for age, the rate did not differ statistically between the groups (p=0.091). The interval cancer rate was 1.7/1000 screening examinations for non-immigrants, 2.4/1000 for immigrants from Western countries and 1.6/1000 for non-Western countries (p<0.001). Histological grade was less favourable for screen-detected cancers, and subtype was less favourable for interval cancers among immigrants from non-Western countries versus non-immigrants. There were no differences in age-adjusted rate of screen-detected cancer among non-immigrants and immigrants from Western countries or non-Western countries among women attending BreastScreen Norway between 2010 and 2019. Small but clinically relevant differences in histopathological tumour characteristics were observed between the three groups.

Diagnostic Performance of a Fecal Immunochemical Test-Based Colorectal Cancer Screening Program According to Ambient Temperature and Humidity.

Simple SummaryHemoglobin degradation can be affected by ambient temperature and humidity. How this modifies the advanced neoplasia detection rate and interval cancer rate remains understudied. We conducted a retrospective study and analyzed the impact of ambient temperature and humidity on the fecal immunochemical test (FIT) positivity rate, detection rate for advanced neoplasia, and interval colorectal cancer (CRC). The results of our study indicated that at >24 °C, the positivity rate was lower, whereas the detection rate of the FIT for advanced neoplasia and the interval cancer detection rate were not affected, probably because we have adopted measures to minimize the impact of ambient temperature on FIT sensitivity. Humidity did not affect FIT sensitivity. The results emphasize the importance of organizational efforts on the procedures along the screening process (such as the cold chain) to minimize the effect of seasonal variations in temperature on the positivity rate.Exposure of the fecal immunochemical test (FIT) to different ambient temperatures and humidity is unavoidable in population-based screening programs in Southern European countries, and it could lead to a decrease in target colorectal lesions. The objective was to evaluate the effect of ambient temperature and humidity on the FIT sensitivity in a population-based screening program for colorectal cancer (CRC) using an ecological design. The retrospective cohort included individuals aged 50–69 years who participated in CRC screening (Barcelona) from 2010–2015, and were followed until 2017 to identify interval CRCs. The positivity rate, and detection rates for advanced polyps and CRC were compared according to ambient temperature, humidity, and quarters of the year. A positive FIT was defined as the detection of ≥20 μg Hb/g in feces. The monthly ambient temperature and humidity were recorded on the day that the FIT was performed. In total, 92,273 FIT results from 53,860 participants were analyzed. The FIT positivity rate was lower at >24 °C than at ≤24 °C (p = 0.005) but was not affected by humidity. The temperature’s impact on positivity did not lead to a decrease in the FIT detection rate for advanced neoplasia or the interval cancer detection rate in a program where the samples were refrigerated until the analysis and screening invitations were discontinued in July and August.

Abstract P2-10-05: The estimated impact of COVID-19 on population breast cancer screening outcomes, and options for risk-based recovery

Abstract OBJECTIVES AND RATIONALE Estimating the impact of COVID-19 on cancer screening programs and related outcomes can help health services prepare for potential delays in diagnoses and different demands on treatment services and plan for best approaches to recovery. Simulation modelling enables estimation of outcomes for a range of scenarios. In this study, we estimate the impact of various disruptions and recovery strategies for the Australian biennial mammographic breast screening program (BreastScreen). METHOD Policy1-Breast is a continuous-time, multiple-cohort micro-simulation model that simulates the whole Australian female population, incorporating breast cancer risk and natural history, breast density, menopause, hormone therapy use and breast cancer screening. Firstly, in the early stages of the COVID pandemic we used Policy1-Breast to evaluate how 3, 6, 9 and 12-month pauses to BreastScreen would impact on population-level breast cancer diagnoses, tumour staging, and breast cancer survival, compared to business-as-usual (BAU) outcomes. Secondly, to explore options for recovery after an actual one-month screening pause in April 2020, we evaluated a range of assumed throughput levels following screening resumption (50% or 80% up to December, then 100% to 120% from Jan 2021), comparing various protocols where specific sub-groups of clients were prioritised for screening during the recovery period. Outcomes are reported for the target age range for the BreastScreen program (50-74 years). RESULTS For 3- to 12-month pauses, we estimated a slight reduction in 5-year survival following diagnosis for women directly affected by a pause, but no discernible changes to population-level breast cancer mortality rates up to 2023. We estimated marked fluctuations in population rates of invasive breast cancer diagnoses with a 10% increase in cancer diagnoses between 2020-2021 and 2022-2023. For a 12-month pause to screening we estimate that population-level breast cancers would increase in size (with an additional 4% &amp;gt;15mm at diagnosis) and be more likely to involve the nodes (increasing from 26% to 30% of all cancers). We estimate that median screening intervals during 2020-2021 would increase from 104 weeks under BAU up to 130 weeks with a 12-month pause, and BreastScreen recall rates and false positive recall rates would fluctuate markedly over time. For the second evaluation of a one-month pause followed by various throughput and prioritisation scenarios, we estimated that screen-detected cancer rates would vary markedly with throughput but interval cancer rates would not, leading to fluctuations in program sensitivity of up to 6%. Reflecting the periodic nature of screening participation, we estimated the extent to which longer-term future screening participation rates are expected echo the peaks and troughs in participation due to the impacts of the COVID pandemic in 2020. We estimate that for a given throughput assumption, client prioritisation could lead to different rescreening rates, screening intervals, and time required for prioritisation protocols, with little change to cancer outcomes. CONCLUSION These modelled evaluations estimate short and longer-term effects of COVID-19 on the impact of population breast cancer screening in Australia. The estimated changes in breast cancer rates and characteristics would be expected to have a flow-on effect on the demand for treatment services in terms of throughput and case-mix. Preparing for such outcomes is critical given that treatment services are also directly impacted by the pandemic. The modelled outcomes are likely to be relevant to other high-income settings with established population breast cancer screening programs. Citation Format: Pietro Procopio, Sabine Deij, Louiza S Velentzis, Amanda Tattam, Lara Petelin, Carolyn Nickson. The estimated impact of COVID-19 on population breast cancer screening outcomes, and options for risk-based recovery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-05.

Populatıon-based breast cancer screenıng program ın Turkey: Priliminary results

Introduction: In Turkey, a population-based breast cancer screening program for women aged 40 to 69 years old was recently introduced. The goal of this study was to document early outcomes and assess the program's success.Method: This study looked at the 348,638 women who were screened in 2016. For end results, all data was gathered from the national centralized reporting system and the Cancer Registry database. For benign discoveries, Breast Imaging-Reporting and Data System (BI-RADS) 1-2 were applied, and for recalls, BI-RADS 0, 4, or 5 were utilized, depending on the level of suspicion. The study looked at the age distribution, recall rate, cancer detection, and interval cancer rates. The stages of identified malignancies were examined and compared to those of the nonscreened group throughout the same time frame.Results: In the screening population, 43.2 percent of women were between the ages of 40 and 49, and 56.8% were between the ages of 50 and 69. The age range of 50–69 was responsible for 70% of screen-detected malignancies. The total recall rate (n = 19,607) was 5.6 percent. The malignancy rate for BI-RADS 5 recalls was 70.2 percent, 19.2 percent for BI-RADS 4, and 1.7 percent for BI-RADS 0 recalls. Screen-discovered malignancies were detected at a rate of 3.2 per 1000 screening exams (n = 1,120). When compared to the Non screened group, the screened group had a larger percentage of early-stage illness (54.3%). (46.7 percent). Interval cancers were discovered in 231 women (0.66 per 1000 screened women).Conclusion: Turkey's recently launched population-based breast cancer screening program appears to be viable and successful, according to preliminary results. According to this study, the breast cancer screening program should be sustained, with coverage of the target group rising.

Missed Breast Cancers on MRI in High-Risk Patients: A Retrospective Case-Control Study.

Purpose: To determine if MRI features and molecular subtype influence the detectability of breast cancers on MRI in high-risk patients. Methods and Materials: Breast cancers in a high-risk population of 104 patients were diagnosed following MRI describing a BI-RADS 4–5 lesion. MRI characteristics at the time of diagnosis were compared with previous MRI, where a BI-RADS 1–2–3 lesion was described. Results: There were 77 false-negative MRIs. A total of 51 cancers were overlooked and 26 were misinterpreted. There was no association found between MRI characteristics, the receptor type and the frequency of missed cancers. The main factors for misinterpreted lesions were multiple breast lesions, prior biopsy/surgery and long-term stability. Lesions were mostly overlooked because of their small size and high background parenchymal enhancement. Among missed lesions, 50% of those with plateau kinetics on initial MRI changed for washout kinetics, and 65% of initially progressively enhancing lesions then showed plateau or washout kinetics. There were more basal-like tumours in BRCA1 carriers (50%) than in non-carriers (13%), p = 0.0001, OR = 6.714, 95% CI = [2.058–21.910]. The proportion of missed cancers was lower in BRCA carriers (59%) versus non-carriers (79%), p < 0.05, OR = 2.621, 95% CI = [1.02–6.74]. Conclusions: MRI characteristics or molecular subtype do not influence breast cancer detectability. Lesions in a post-surgical breast should be assessed with caution. Long-term stability does not rule out malignancy and multimodality evaluation is of added value. Lowering the biopsy threshold for lesions with an interval change in kinetics for a type 2 or 3 curve should be considered. There was a higher rate of interval cancers in BRCA 1 patients attributed to lesions more aggressive in nature.

Evidence from a BreastScreen cohort does not support a longer inter-screen interval in women who have no conventional risk factors for breast cancer.

ObjectivesTo determine screening outcomes in women who have no recorded risk factors for breast cancer.MethodsA retrospective population-based cohort study included all 1,026,137 mammography screening episodes in 323,082 women attending the BreastScreen Western Australia (part of national biennial screening) program between July 2007 and June 2017. Cancer detection rates (CDR) and interval cancer rates (ICR) were calculated in screening episodes with no recorded risk factors for breast cancer versus at least one risk factor stratified by age. CDR was further stratified by timeliness of screening (<27 versus ≥27 months); ICR was stratified by breast density.ResultsAmongst 566,948 screens (55.3%) that had no recorded risk factors, 2347 (40.9%) screen-detected cancers were observed. In screens with no risk factors, CDR was 50 (95%CI 48–52) per 10,000 screens and ICR was 7.9 (95%CI 7.4–8.4) per 10,000 women-years, estimates that were lower than screens with at least one risk factor (CDR 83 (95%CI 80–86) per 10,000 screens, ICR 12.2 (95%CI 11.5–13.0) per 10,000 women-years). Compared to timely screens with risk factors, delayed screens with no risk factors had similar CDR across all age groups and a higher proportion of node positive cancers (26.1% vs 20.7%). ICR was lowest in screens that had no risk factors nor dense breasts in all age groups.ConclusionsMajority of screens had no recorded breast cancer risk factors, hence a substantial proportion of screen-detected cancers occur in these screening episodes. Our findings may not justify less frequent screening in women with no risk factors.

Association of Regular Endoscopic Screening with Interval Gastric Cancer Incidence in the National Cancer Screening Program.

Although regular endoscopic screening may help in early detection of gastric cancer, interval cancer remains a problem in the screening program. This study evaluated the association between regular endoscopic screening and interval cancer detection in the Korean National Cancer Screening Program (KNCSP). We defined three groups (regularly, irregularly, and not screened) according to the screening interval, and the trends in the interval cancer rate (ICR) between the groups were tested using the Cochran–Armitage test. The influence of regular endoscopic screening on the risk of interval cancer was evaluated using multivariable logistic regression. Among the 11,642,410 participants who underwent endoscopy, the overall ICR was 0.36 per 1000 negative screenings. The ICR of the not screened group (0.41) was the highest among the three groups and the risk of interval cancer in this group was 1.68 times higher (p < 0.001) than that in the regularly screened group. Women in their 40s who had regular screening with no history of intestinal metaplasia and gastric polyps would have the lowest probability of having interval cancer (0.005%). Regular participation in endoscopic screening programs for reducing the risk of interval cancer may help to improve the quality of screening programs.

Lapses in breast cancer screening for highly penetrant mutation carriers during pregnancy and lactation.

Screening for breast cancer in highly penetrant mutation carriers during pregnancy and lactation is challenging and consensus guidelines are lacking. This study evaluates the lapse in screening and the interval pregnancy-associated breast cancer rate. A single-institution retrospective cohort study of pregnant and lactating patients with known pathogenic germline mutations was performed. Lapse in screening was defined as the interval between the last screening imaging exam obtained before last menstrual period and the subsequent screening imaging. Out of 685 patients, 42 had 1-3 evaluable pregnancies (54 total - 28 managed in High Risk Breast Clinic and 26 by OB/GYN). Mutations were observed in patients in BRCA1 (49%), BRCA2 (36%), CDH1 (5%), CHEK2 (2%), ATM (2%), NF1 (3%), and MSH2 (3%). The average screening lapse was 25 [19, 30] months for patients followed in the High Risk Clinic versus 32.5 [21, 65.75] months for patients followed with Routine Care (p = 0.035). We identified three cases of pregnancy-associated breast cancer (interval cancer rate 6%). Patients with highly penetrant mutations are at risk for the development of interval pregnancy-associated breast cancer. Development of consistent screening guidelines and adherence to those guidelines is needed for this patient population.

EP.TU.660The rate of interval colorectal cancer within 5 years of a negative colonoscopy at a district general hospital

Abstract Aims Interval colorectal cancer is defined as cancer that has developed within a short interval of a diagnostic test that did not detect a cancer. Many authors define this interval as five years, though more complex definitions of interval cancer have been proposed. Our aim was to determine what percentage of colorectal cancers diagnosed at our hospital had a negative colonoscopy within the 5 years prior to their diagnosis. Methods We obtained details of all colorectal cancers diagnosed between 2017-2019 at our department. We then surveyed the endoscopy system to detect the patients who had a negative colonoscopy within the 5 years prior to their diagnosis, to calculate what percentage of cancers diagnosed within that period were interval cancers. Results Between 2017-2019, 539 patients were diagnosed with colorectal cancer. Age at diagnosis varied widely from 21 to 107, and 310 (57.5%) of patients were male. Seventeen patients had a negative colonoscopy within 5 years (though two of these were planned repeat procedures within a few months of the index ‘negative’ colonoscopy). We can therefore calculate the rate of interval cancer at 3.1% between 2017-2019. Conclusions The aetiology of interval colorectal cancer has been attributed to patient/tumour factors (right colon and female sex) and technical factors (adenoma detection and caecal intubation rate). Though the rate of interval cancer at our department seems pleasingly low compared to the literature, we plan to investigate the risk factors that might be at play: are biological factors to blame or can our endoscopy service be improved?

Digital breast tomosynthesis (DBT) plus synthesised two-dimensional mammography (s2D) in breast cancer screening is associated with higher cancer detection and lower recalls compared to digital mammography (DM) alone: results of a systematic review and meta-analysis

ObjectivesDigital breast tomosynthesis (DBT) plus digital mammography (DM) in screening is problematic due to increased radiation by the double exposure. Synthesised two-dimensional mammography (s2D) calculated from DBT datasets at no additional dose appears a sensible alternative compared to adding DM. This systematic review and meta-analysis focuses on screening performance outcomes in women screened with DBT plus s2D compared to DM alone.MethodsPubMed was searched from January 1, 2010, to September 2, 2020. Studies comparing DBT plus s2D to DM alone in breast cancer screening were included. Pooled risk ratios (RR) were estimated for cancer detection rates (CDR), recall rates, interval cancer rates (ICR), biopsy rates, and positive predictive values for recalls (PPV-1), for biopsies recommended (PPV-2), and for biopsies performed (PPV-3). Sensitivity analyses were performed using the leave-one-out approach. Risk of bias (RoB) was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool.ResultsTwelve papers covering 414,281 women were included from 766 records identified. CDR is increased ([RR, 95% CI] 1.35, 1.20–1.52), recall rates are decreased (0.79, 0.64–0.98), and PPV-1 is increased (1.69, 1.45–1.96) when using DBT plus s2D compared to DM alone. ICR and biopsy rates did not differ, but PPV-2 respectively PPV-3 increased with DBT plus s2D (1.57, 1.08–2.28 respectively 1.36, 1.17–1.58). Overall RoB of studies was assessed to be low.ConclusionResults show improved diagnostic outcomes with DBT plus s2D compared to DM alone and underline the value of DBT in combination with s2D in breast cancer screening.Key Points• DBT plus s2D is associated with higher CDR, lower recall rates, and a higher PPV-1 compared to DM alone in breast cancer screening.• No differences in biopsy rates were found between screening modalities, but PPV-2 and PPV-3 were higher in women screened with DBT plus s2D compared to DM alone.• We identified inconsistent results of ICR in two studies comparing DBT plus s2D to DM alone—resulting in no differences when pooling ICR in meta-analysis.

1302 Ratio of Adenoma Detection Rate to Polyp Detection Rate

Abstract Introduction Colorectal cancer is the 3rd most common cancer in the UK. The higher Adenoma Detection Rate during colonoscopy is associated with reduction in the mortality incidence of colorectal cancer. Endoscopists with less than 20% ADR is directly proportional to higher risk of the development of an interval Colorectal cancer. The aim of this study was to calculate the Adenoma Detection Rate and Polyp Detection Rate for each endoscopist to assess the performance of the unit as well as individuals. Method A retrospective analysis was conducted for patients who had colonoscopy in a period of 3 consecutive months at a primary care hospital in England. This study included collecting the data through patient’s histology reports and medical records. The primary outcome was total Adenoma Detection Rate and Polyp Detection Rate and its ratio for each endoscopist. Results 913 colonoscopies were done by 16 different endoscopists out of which 279 patients with polyps were considered for the study. It was observed that half of the total endoscopists were found to have ADR more than 20%. 4 endoscopists had ADR between 15-20% whereas below minimal rate (less than 15%) ADR was recorded by the other 4 endoscopists. Conclusions Lower ADRs are associated with higher rates of interval cancers. An improvement of the ADR of 1% prevents 3% people from colon cancer which can be achieved by maintaining the aspirational adenoma detection rate more than 20%.

Varying fecal immunochemical test screening cutoffs by age and gender: a way to increase detection rates and reduce the number of colonoscopies

Most colorectal cancer (CRC) screening programs based on the fecal immunochemical test (FIT) use the same cutoff value for all participants. This study aimed at finding age- and gender-specific cutoff values that can improve population-based CRC screening. This observational study used data from the first 2 years of the Danish FIT-based CRC screening program to estimate sensitivity, specificity, number of positive tests, number of screen-detected cancers and adenomas, and number of interval cancers for various cutoff values for different male and female age groups. Data from 531,828 participants showed that lower cutoff values for older residents and higher cutoff values for younger residents increased the overall sensitivity and specificity, decreased the number of needed colonoscopies by 7%, increased the number of screen-detected cancer by 1.1%, increased the number of screen-detected adenomas by 5%, and decreased the number of interval cancers by approximately 1.5%. However, these cutoff values also increased an inequality in sensitivity and specificity. Choosing cutoff values that ensured equal sensitivity between the groups, however, did increase inequality in, for example, the interval cancer rate. In a FIT-based CRC program it is possible to decrease the number of needed colonoscopies while at the same time to increase overall sensitivity and specificity and detect more cancers and adenomas by using different cutoff values for different male and female age groups. However, this increases inequality in sensitivity and specificity, whereas other strategies like ensuring equal sensitivity could be considered.

Trends in the Performance of the Korean National Cancer Screening Program for Gastric Cancer from 2007 to 2016.

PurposeThe Korean National Cancer Screening Program (KNCSP) has implemented two screening methods for gastric cancer— upper gastrointestinal series (UGIS) and endoscopy—for Koreans aged ≥ 40 years. We aimed to assess performance trends for both screening methods.Materials and MethodsThe KNCSP database was used to evaluate individuals who underwent screening from 2007 to 2016. The final gastric cancer diagnosis was ascertained by linking with the Korean Central Cancer Registry. We conducted a prospective, cross-sectional analysis to estimate performance indicators of gastric cancer screening by UGIS and endoscopy, stratified by sociodemographic factors.ResultsWe found that screening rates for gastric cancer increased from 28% to 51.7% between 2007 and 2016, and that the rate of endoscopy use for gastric cancer screening increased sharply. Cancer detection rates (CDR) of UGIS and endoscopy were 0.41 and 2.25 per 1,000 screens in 2007–2008 and 0.26 and 1.99 in 2015–2016, respectively. Interval cancer rates (ICR) per 1,000 negative screenings were 1.33 (2007–2008) and 1.21 (2015–2016) for UGIS and 1.14 (2007–2008) and 0.88 (2015–2016) for endoscopy. The sensitivity of UGIS decreased from 23.6% (2007–2008) to 17.6% (2015–2016), whereas that of endoscopy increased from 66.4% (2007–2008) to 69.3% (2015–2016). Specificity was maintained at > 99% for both methods over the study period.ConclusionThe use of endoscopy for gastric cancer screening within the KNCSP has increased. Endoscopy has higher CDR, sensitivity, and specificity, and lower ICR estimates than does UGIS.

Significant decrease in interval colorectal cancer incidence after implementing immunochemical testing in a multiple-round guaiac-based screening programme.

We aimed to evaluate the effects of switching to faecal immunochemical testing (FIT) on the cumulative 2-year incidence rate of interval cancers, interval cancer rate and test sensitivity within a mature population-based colorectal cancer screening programme consisting of six rounds of biennial guaiac faecal occult blood testing (gFOBT). The FIT results were compared with those of gFOBT used in each of the previous two rounds. For the three rounds analysed, 279,041 tests were performed by 156,186 individuals. Logistic regression analysis was used to determine interval cancer risk factors (Poisson regression) and to compare the sensitivity of FIT to gFOBT. There were 612 cases of screen-detected cancers and 209 cases of interval cancers. The sex- and age-adjusted cumulative 2-year incidence rates of interval cancers were 55.7 (95% CI, 45.3-68.5), 42.4 (95% CI, 32.6-55.2) and 15.8 (95% CI, 10.9-22.8) per 100,000 person-years after the last two rounds of gFOBT and FIT, respectively. The FIT/gFOBT incidence rate ratio was 0.38 [95% CI, 0.27-0.54] (P < 0.001). Sex- and age-adjusted sensitivity was significantly higher with FIT than with gFOBT (OR = 6.70 [95% CI, 4.48-10.01], P < 0.0001). This population-based study revealed a dramatic decrease in the cumulative incidence rates of interval cancers after switching from gFOBT to FIT. These data provide an additional incentive for countries still using gFOBT to switch to FIT.

965The estimated impact of improved breast screening tests targeted at women with dense breasts

Abstract Background There is increasing interest in risk-based breast cancer screening, including interventions to improve outcomes for women with mammographically dense breasts. Methods Policy1-Breast is a continuous-time, multiple-cohort micro-simulation whole-population model which incorporates breast cancer risk, life-course breast density, menopause, hormone therapy use and screening participation. Outcomes include cancer diagnoses and characteristics (invasive/DCIS, tumour size, grade), mode of detection (screen-detected/interval/other) and mortality (breast cancer and other cause). Policy1-Breast validates well against key observed clinical outcomes in Australia. We estimate changes in outcomes within and outside the BreastScreen program upon the introduction of a hypothetical screening test with improved sensitivity for women with dense breasts. Results We estimate that introducing in year 2020 a screening test for women in the highest quintile of breast density at age 50 that halves the masking effect of their breast density would, by 2026-2030, increase diagnosis rates of population-level invasive cancers ( 10%) and screen-detected cancers (20%) and decrease rates of interval cancers (17%) and community-detected cancers (6%). Conclusions Targeted screening tests with improved sensitivity for women with dense breasts are expected to markedly reduce interval cancers and other cancers diagnosed outside the BreastScreen program, while increasing all cancer diagnoses due to increased rates of screen-detected cancers. Key messages Specialised breast cancer screening tests directed at women with very high breast density are expected to reduce interval cancers and increase overall cancer diagnoses. Population simulation models such as Policy1-Breast can complement trial evidence by evaluating a range of scenarios and estimating short and long-term implications.

Evaluation of Adjunctive Ultrasonography for Breast Cancer Detection Among Women Aged 40-49 Years With Varying Breast Density Undergoing Screening Mammography

Mammography has limited accuracy in breast cancer screening. Ultrasonography, when used in conjunction with mammography screening, is helpful to detect early-stage and invasive cancers for asymptomatic women with dense and nondense breasts. To evaluate the performance of adjunctive ultrasonography with mammography for breast cancer screening, according to differences in breast density. This study is a secondary analysis of the Japan Strategic Anti-cancer Randomized Trial. Between July 2007 and March 2011, asymptomatic women aged 40 to 49 years were enrolled in Japan. The present study used data from cases enrolled from the screening center in Miyagi prefecture during 2007 to 2020. Participants were randomly assigned in a 1:1 ratio to undergo either mammography with ultrasonography (intervention group) or mammography alone (control group). Data analysis was performed from February to March 2020. Ultrasonography adjunctive to mammography for breast cancer screening regardless of breast density. Sensitivity, specificity, recall rates, biopsy rates, and characteristics of screen-detected cancers and interval breast cancers were evaluated between study groups and for each modality according to breast density. A total of 76 119 women were enrolled, and data for 19 213 women (mean [SD] age, 44.5 [2.8] years) from the Miyagi prefecture were analyzed; 9705 were randomized to the intervention group and 9508 were randomized to the control group. A total of 11 390 women (59.3%) had heterogeneously or extremely dense breasts. Among the overall group, 130 cancers were found. Sensitivity was significantly higher in the intervention group than the control group (93.2% [95% CI, 87.4%-99.0%] vs 66.7% [95% CI, 54.4%-78.9%]; P < .001). Similar trends were observed in women with dense breasts (sensitivity in intervention vs control groups, 93.2% [95% CI, 85.7%-100.0%] vs 70.6% [95% CI, 55.3%-85.9%]; P < .001) and nondense breasts (sensitivity in intervention vs control groups, 93.1% [95% CI, 83.9%-102.3%] vs 60.9% [95% CI, 40.9%-80.8%]; P < .001). The rate of interval cancers per 1000 screenings was lower in the intervention group compared with the control group (0.5 cancers [95% CI, 0.1-1.0 cancers] vs 2.0 cancers [95% CI, 1.1-2.9 cancers]; P = .004). Within the intervention group, the rate of invasive cancers detected by ultrasonography alone was significantly higher than that for mammography alone in both dense (82.4% [95% CI, 56.6%-96.2%] vs 41.7% [95% CI, 15.2%-72.3%]; P = .02) and nondense (85.7% [95% CI, 42.1%-99.6%] vs 25.0% [95% CI, 5.5%-57.2%]; P = .02) breasts. However, sensitivity of mammography or ultrasonography alone did not exceed 80% across all breast densities in the 2 groups. Compared with the control group, specificity was significantly lower in the intervention group (91.8% [95% CI, 91.2%-92.3%] vs 86.8% [95% CI, 86.2%-87.5%]; P < .001). Recall rates (13.8% [95% CI, 13.1%-14.5%] vs 8.6% [95% CI, 8.0%-9.1%]; P < .001) and biopsy rates (5.5% [95% CI, 5.1%-6.0%] vs 2.1% [95% CI, 1.8%-2.4%]; P < .001) were significantly higher in the intervention group than the control group. In this secondary analysis of a randomized clinical trial, screening mammography alone demonstrated low sensitivity, whereas adjunctive ultrasonography was associated with increased sensitivity. These findings suggest that adjunctive ultrasonography has the potential to improve detection of early-stage and invasive cancers across both dense and nondense breasts. Supplemental ultrasonography should be considered as an appropriate imaging modality for breast cancer screening in asymptomatic women aged 40 to 49 years regardless of breast density. NIPH Clinical Trial Identifier: UMIN000000757.