Evaluating the effectiveness of population-based breast cancer service screening: an analysis of parsimonious patient survival information with the time-varying Cox model.

BACKGROUND: This study is aimed at estimating the unbiased effectiveness of population-based breast cancer service screening based on case survival information alone rather than large-scale individual screening data pursuant to the intention-to-treat principle of a randomized-controlled trial. METHODS: A novel time-dependent switched design with two modalities of cancer detection (screen-detected vs clinically detected) was proposed to evaluate the effectiveness of breast cancer screening. We used data on 767 patients from Kopparberg in the Swedish Two-County trial and on 78 587 patients in the Taiwan population-based service screening. We estimated the relative rate of the screen-detected vs the clinically detected with adjustment for both truncation and lead-time biases. The absolute effectiveness in terms of the number needed to screen (NNS) for averting one death from breast cancer was estimated. RESULTS: The relative rate of effectiveness was estimated as 33%, which was consistent with the 37% reported from the original Swedish randomized-controlled trial. The corresponding estimate for the Taiwan screening programme was 42%, which was also very close to that estimated using individual screening history data (41%). Both relative estimates were further applied to yield 446 and 806 of NNS for averting one death from breast cancer for the corresponding two data sets. CONCLUSION: The proposed time-dependent switched design and analysis with two modalities of case survival information provides a very efficient means for estimating the unbiased estimates of relative and absolute effectiveness of population-based breast cancer service screening dispensing with a large amount of individual screening history data.

A new approach to breast cancer terminology based on the anatomic site of tumour origin: The importance of radiologic imaging biomarkers.

PURPOSE: To use mammographic tumour features (imaging biomarkers) to classify breast cancer according to its apparent anatomic site of origin in the new era where tumours are found at their nonpalpable, earliest detectable phase. METHOD: Large format, subgross, three-dimensional histopathologic images of breast cancer subtypes and their corresponding imaging biomarkers were correlated with large format thin section histopathology and long-term patient outcome. RESULTS: This systematic correlation indicates that breast cancers arise from three separate fibroglandular tissue components: the terminal ductal lobular units (TDLUs), the major lactiferous ducts, and in the stem cells of the mesenchyme. The resulting three cancer subgroups have distinctly different clinical, histopathological and mammographic presentations and different long-term outcomes. The relative frequency of these three breast cancer subgroups is approximately 75%, 20% and 5%, respectively. Classification of breast cancers according to their anatomic site of origin, as demonstrated with breast imaging and confirmed by subgross histopathology, correlates closely with the long-term patient outcome. CONCLUSIONS: Classification of breast cancers according to their site of origin helps overcome the inconsistencies in the current histopathologic terminology with its ductal-lobular dichotomy. The ability of the imaging biomarkers to determine the site of tumour origin and serve as a prognostic indicator emphasizes the increasingly crucial role of breast imaging in the management of breast cancer. Basing breast cancer management upon anatomically relevant terminology challenges the conventional mindset. Our proposals are based on research results from an unprecedented number of prospectively collected nonpalpable breast cancers diagnosed at their earliest detectable phases and followed up for several decades. This article is a general introduction to a series of forthcoming articles describing in detail the breast malignancies originating from the three sites of origin.

Modelling the impacts of COVID-19 pandemic on the quality of population-based colorectal cancer screening.

COVID-19 pandemic has severely affected regular public health interventions including population-based cancer screening. Impacts of such screening delays on the changes in structure and screening process and the resultant long-term outcomes are unknown. It is therefore necessary to develop a systematic framework to assess theses impacts related to these components of quality. Using population-based cancer screening with fecal immunochemical test (FIT) as an illustration, the main analysis was to assess how various scenarios of screening delays were associated with the capacity for primary screening and full time equivalent (FTE) for colonoscopy and impact long-term outcomes based on a Markov decision tree model on population level. The second analysis was to quantify how the extent of COVID-19 epidemic measured by social distancing index affected capacity and FTE that were translated to delays with an exponential relationship. COVID-19 epidemic led to 25%, 29%, 34%, and 39% statistically significantly incremental risks of late cancer for the delays of 0.5-year, 1-year,1.5-year, and 2-year, respectively compared with regular biennial FIT screening. The corresponding statistically findings of four delayed schedules for death from colorectal cancer (CRC) were 26%, 28%, 29%, and 30%, respectively. The higher social distancing index led to a lower capacity of uptake screening and a larger reduction of FTE, resulting in longer screening delay and longer waiting time, which further impacted long-term outcomes as above. In summary, a systematic modelling approach was developed for demonstrating the strong impact of screening delays caused by COVID-19 epidemic on long-term outcomes illustrated with a Taiwan population-based FIT screening of CRC.

Mitigating the impact of COVID-19 on colorectal cancer screening: Organized service screening perspectives from the Asia-Pacific region.

Colorectal cancer(CRC) is one of the most prevalent malignancies in the Asia-Pacific region, and many countries in this region have launched population CRC service screening. In this study, CRC screening key indicators, including the FIT(fecal immunochemical test) screening rate (or participation rate) and the rate of undergoing colonoscopy after positive FIT in 2019 and 2020, were surveyed in individual countries in the Asia-Pacific region. The impact of the pandemic on the effectiveness of CRC screening was simulated given different screening rates and colonoscopy rates and assuming the pandemic would persist or remain poorly controlled for a long period of time, using the empirical data from the Taiwanese program and the CRC natural history model. During the COVID-19 pandemic, most of the programs in this region were affected, but to different extents, which was largely influenced by the severity of the local pandemic. Most of the programs continued screening services in 2020, although a temporary pause occurred in some countries. The modeling study revealed that prolonged pauses of screening led to 6% lower effectiveness in reducing CRC mortality. Screening organizers should coordinate with health authorities to elaborate on addressing screening backlogs, setting priorities for screening, and applying modern technologies to overcome potential obstacles. Many novel approaches that were developed and applied during the COVID-19 pandemic, such as the risk-stratified approach that takes into account personal CRC risk and the local epidemic status, as well as new digital technologies, are expected to play important roles in CRC screening in the future.

Beneficial Effect of Consecutive Screening Mammography Examinations on Mortality from Breast Cancer: A Prospective Study.

Background Previously, the risk of death from breast cancer was analyzed for women participating versus those not participating in the last screening examination before breast cancer diagnosis. Consecutive attendance patterns may further refine estimates. Purpose To estimate the effect of participation in successive mammographic screening examinations on breast cancer mortality. Materials and Methods Participation data for Swedish women eligible for screening mammography in nine counties from 1992 to 2016 were linked with data from registries and regional cancer centers for breast cancer diagnosis, cause, and date of death (Uppsala University ethics committee registration number: 2017/147). Incidence-based breast cancer mortality was calculated by whether the women had participated in the most recent screening examination prior to diagnosis only (intermittent participants), the penultimate screening examination only (lapsed participants), both examinations (serial participants), or neither examination (serial nonparticipants). Rates were analyzed with Poisson regression. We also analyzed incidence of breast cancers proving fatal within 10 years. Results Data were available for a total average population of 549 091 women (average age, 58.9 years ± 6.7 [standard deviation]). The numbers of participants in the four groups were as follows: serial participants, 392 135; intermittent participants, 41 746; lapsed participants, 30 945; and serial nonparticipants, 84 265. Serial participants had a 49% lower risk of breast cancer mortality (relative risk [RR], 0.51; 95% CI: 0.48, 0.55; P < .001) and a 50% lower risk of death from breast cancer within 10 years of diagnosis (RR, 0.50; 95% CI: 0.46, 0.55; P < .001) than serial nonparticipants. Lapsed and intermittent participants had a smaller reduction. Serial participants had significantly lower risk of both outcomes than lapsed or intermittent participants. Analyses correcting for potential biases made little difference to the results. Conclusion Women participating in the last two breast cancer screening examinations prior to breast cancer diagnosis had the largest reduction in breast cancer death. Missing either one of the last two examinations conferred a significantly higher risk. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Stephen A. Feig in this issue.

Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers.

OBJECTIVE: To measure the effects of faecal immunochemical test (FIT) for colorectal cancer (CRC) screening on overall and site-specific long-term effectiveness of population-based organised service screening. DESIGN: A prospective cohort study of Taiwanese nationwide biennial FIT screening was performed. A total of 5 417 699 eligible subjects were invited to attend screening from 2004 through 2009 and were followed up until 2014. We estimated the adjusted relative rates (aRRs) on the effectiveness of reducing advanced-stage CRC (stage II+) and CRC death by Bayesian Poisson regression models with the full adjustment for a cascade of self-selection factors (including the screening rate and the colonoscopy rate) and the completeness of colonoscopy together with demographic features. RESULTS: FIT screening (exposed vs unexposed) reduced the incidence of advanced-stage CRC (48.4 vs 75.7 per 100 000) and mortality (20.3 vs 41.3 per 100 000). Statistically significant reductions of both incidence of advanced-stage CRCs (aRR=0.66, 95% CI 0.63 to 0.70) and deaths from CRC (aRR=0.60, 95% CI 0.57 to 0.64) were noted. FIT screening was more effective in reducing distal advanced-stage CRCs (aRR=0.61, 95% CI 0.58 to 0.64) and CRC mortality (aRR=0.56, 95% CI 0.53 to 0.69) than proximal advanced CRCs (aRR=0.84, 95% CI 0.77 to 0.92) and CRC mortality (aRR=0.72, 95% CI 0.66 to 0.80). CONCLUSION: A large-scale population-based biennial FIT screening demonstrates 34% significant reduction of advanced-stage CRCs and 40% reduction of death from CRC with larger long-term effectiveness in the distal colon than the proximal colon. Our findings provide a strong and consistent evidence-based policy for supporting a sustainable population-based FIT organised service screening worldwide. The disparity of site-specific long-term effectiveness also provides an insight into the remedy for lower effectiveness of FIT screening in the proximal colon.