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Background: Among randomized trials evaluating flexible sigmoidoscopy (FSG) for its effect on colorectal cancer mortality, only the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial screened its participants more than one time. We report outcomes from the PLCO screening FSG program and evaluate the increased yield produced by a second FSG.Methods: Participants were screened by 60-cm FSG in 10 regional screening centers at study entry and 3 or 5 years later, depending on the time of random assignment. Results from subsequent diagnostic intervention were tracked and recorded in a standardized fashion, and outcomes were compared according to sex and age. The protocol discouraged repeat FSG in persons with colorectal cancer or adenoma diagnosed after the initial FSG.Results: Of 77 447 enrollees, 67 073 (86.6%) had at least one FSG and 39 443 (50.9%) had two FSGs. Diagnostic intervention occurred in 74.9% after a positive first FSG and in 78.7% after a positive repeat FSG. The second FSG increased the screening yield by 32%: Colorectal cancer or advanced adenoma was detected in 37.8 per 1000 persons after first screening and in 49.8 per 1000 persons after all screenings. The second FSG increased the yield of cancer or advanced adenoma by 26% in women and by 34% in men. Of 223 subjects who received a diagnosis of colorectal carcinoma within 1 year of a positive FSG, 64.6% had stage I and 17.5% had stage II disease.Conclusions: Repeat FSG increased the detection of colorectal cancer or advanced adenoma in women by one-fourth and in men by one-third. Screen-detected carcinomas were early stage (stage I or II) in greater than 80% of screened persons. Colorectal cancer mortality data from the PLCO, as the definitive endpoint, will follow in later publications. [ABSTRACT FROM AUTHOR]

Background and Study Aim: Inadequate colorectal cancer screening wastes limited endoscopic resources. We examined patients factors associated with inadequate flexible sigmoidoscopy (FSG) screening at baseline screening and repeat screening 3-5 years later in 10 geographically-dispersed screening centers participating in the ongoing Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.Methods: A total of 64,554 participants (aged 55-74) completed baseline questionnaires and underwent FSG at baseline. Of these, 39,385 participants returned for repeat screening. We used logistic regression models to assess factors that are associated with inadequate FSG (defined as a study in which the depth of insertion of FSG was <50 cm or visual inspection was limited to <90% of the mucosal surface but without detection of a polyp or mass).Results: Of 7084 (11%) participants with inadequate FSG at baseline, 6496 (91.7%) had <50 cm depth of insertion (75.3% due to patient discomfort) and 500 (7.1%) participants had adequate depth of insertion but suboptimal bowel preparation. Compared to 55-59 year age group, advancing age in 5-year increments (odds ratios (OR) from 1.08 to 1.51) and female sex (OR = 2.40; 95% confidence interval (CI): 2.27-2.54) were associated with inadequate FSG. Obesity (BMI > 30 kg/m(2)) was associated with reduced odds (OR = 0.67; 95% CI: 0.62-0.72). Inadequate FSG screening at baseline was associated with inadequate FSG at repeat screening (OR = 6.24; 95% CI: 5.78-6.75).Conclusions: Sedation should be considered for patients with inadequate FSG or an alternative colorectal cancer screening method should be recommended. [ABSTRACT FROM AUTHOR]

Background: Cancer has substantial health, quality-of-life, and economic impacts. Screening may decrease cancer mortality and treatment costs, but the cost of screening in the United States is unknown., Objective: To estimate the annual cost of initial cancer screening (that is, screening without follow-up costs) in the United States in 2021., Design: Model using national health care survey and cost resources data., Setting: U.S. health care systems and institutions., Participants: People eligible for breast, cervical, colorectal, lung, and prostate cancer screening with available data., Measurements: The number of people screened and associated health care system costs by insurance status in 2021 dollars., Results: Total health care system costs for initial cancer screenings in the United States in 2021 were estimated at $43 billion. Approximately 88.3% of costs were attributable to private insurance; 8.5% to Medicare; and 3.2% to Medicaid, other government programs, and uninsured persons. Screening for colorectal cancer represented approximately 64% of the total cost; screening colonoscopy represented about 55% of the total. Facility costs (amounts paid to facilities where testing occurred) were major drivers of the total estimated costs of screening., Limitations: All data on receipt of cancer screening are based on self-report from national health care surveys. Estimates do not include costs of follow-up for positive or abnormal screening results. Variations in costs based on geography and provider or health care organization are not fully captured., Conclusion: The $43 billion estimated annual cost for initial cancer screening in the United States in 2021 is less than the reported annual cost of cancer treatment in the United States in the first 12 months after diagnosis. Identification of cancer screening costs and their drivers is critical to help inform policy and develop programmatic priorities, particularly for enhancing access to recommended cancer screening services., Primary Funding Source: None., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0375.

Background: Lung cancer screening (LCS) using low-dose computed tomography (LDCT) reduces lung cancer mortality but can lead to downstream procedures, complications, and other potential harms. Estimates of these events outside NLST (National Lung Screening Trial) have been variable and lacked evaluation by screening result, which allows more direct comparison with trials., Objective: To identify rates of downstream procedures and complications associated with LCS., Design: Retrospective cohort study., Setting: 5 U.S. health care systems., Patients: Individuals who completed a baseline LDCT scan for LCS between 2014 and 2018., Measurements: Outcomes included downstream imaging, invasive diagnostic procedures, and procedural complications. For each, absolute rates were calculated overall and stratified by screening result and by lung cancer detection, and positive and negative predictive values were calculated., Results: Among the 9266 screened patients, 1472 (15.9%) had a baseline LDCT scan showing abnormalities, of whom 140 (9.5%) were diagnosed with lung cancer within 12 months (positive predictive value, 9.5% [95% CI, 8.0% to 11.0%]; negative predictive value, 99.8% [CI, 99.7% to 99.9%]; sensitivity, 92.7% [CI, 88.6% to 96.9%]; specificity, 84.4% [CI, 83.7% to 85.2%]). Absolute rates of downstream imaging and invasive procedures in screened patients were 31.9% and 2.8%, respectively. In patients undergoing invasive procedures after abnormal findings, complication rates were substantially higher than those in NLST (30.6% vs. 17.7% for any complication; 20.6% vs. 9.4% for major complications)., Limitation: Assessment of outcomes was retrospective and was based on procedural coding., Conclusion: The results indicate substantially higher rates of downstream procedures and complications associated with LCS in practice than observed in NLST. Diagnostic management likely needs to be assessed and improved to ensure that screening benefits outweigh potential harms., Primary Funding Source: National Cancer Institute and Gordon and Betty Moore Foundation., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-0653.

Background: Colorectal cancer screening is universally recommended for adults ages 45 to 75 years. Noninvasive fecal occult blood tests are effective screening tests recommended by guidelines. However, empirical evidence to inform older adults' decisions about whether to continue screening is sparse, especially for individuals with prior screening., Methods: This study used a retrospective cohort of older adults at three Kaiser Permanente integrated healthcare systems (Northern California, Southern California, Washington) and Parkland Health. Beginning 1 year following a negative stool-based screening test, cumulative risks of colorectal cancer incidence, colorectal cancer mortality (accounting for deaths from other causes), and non-colorectal cancer mortality were estimated., Results: Cumulative incidence of colorectal cancer in screen-eligible adults ages 76 to 85 with a negative fecal occult blood test 1 year ago (N = 118,269) was 0.23% [95% confidence interval (CI), 0.20%-0.26%] after 2 years and 1.21% (95% CI, 1.13%-1.30%) after 8 years. Cumulative colorectal cancer mortality was 0.03% (95% CI, 0.02%-0.04%) after 2 years and 0.33% (95% CI, 0.28%-0.39%) after 8 years. Cumulative risk of death from non-colorectal cancer causes was 4.81% (95% CI, 4.68%-4.96%) after 2 years and 28.40% (95% CI, 27.95%-28.85%) after 8 years., Conclusions: Among 76- to 85-year-olds with a recent negative stool-based test, cumulative colorectal cancer incidence and mortality estimates were low, especially within 2 years; death from other causes was over 100 times more likely than death from colorectal cancer., Impact: These findings of low absolute colorectal cancer risk, and comparatively higher risk of death from other causes, can inform decision-making regarding whether and when to continue colorectal cancer screening beyond age 75 among screen-eligible adults., (©2023 American Association for Cancer Research.)

Background: Lung cancer screening (LCS) with low-dose CT (LDCT) imaging was recommended in 2013, making approximately 8 million Americans eligible for LCS. The demographic characteristics and outcomes of individuals screened in the United States have not been reported at the population level., Research Question: What are the outcomes among people screened and entered in the American College of Radiology's Lung Cancer Screening Registry compared with those of trial participants?, Study Design and Methods: This was a cohort study of individuals undergoing baseline LDCT imaging for LCS between 2015 and 2019. Predictors of adherence to annual screening were computed. LDCT scan interpretations by Lung Imaging Reporting and Data System (Lung-RADS) score, cancer detection rates (CDRs), and stage at diagnosis were compared with National Lung Cancer Screening Trial data., Results: Adherence was 22.3%, and predictors of poor adherence included current smoking status and Hispanic or Black race. On baseline screening, 83% of patients showed negative results and 17% showed positive screening results. The overall CDR was 0.56%. The percentage of people with cancer detected at baseline was higher in the positive Lung-RADS categories at 0.4% for Lung-RADS category 3, 2.6% for Lung-RADS category 4A, 11.1% for Lung-RADS category 4B, and 19.9% for Lung-RADS category 4X. The cancer stage distribution was similar to that observed in the National Lung Cancer Screening Trial, with 53.5% of patients receiving a diagnosis of stage I cancer and 14.3% with stage IV cancer. Underreporting into the registry may have occurred., Interpretation: This study revealed both the positive aspects of CT scan screening for lung cancer and the challenges that remain. Findings on CT imaging were correlated accurately with lung cancer detection using the Lung-RADS system. A significant stage shift toward early-stage lung cancer was present. Adherence to LCS was poor and likely contributes to the lower than expected cancer detection rate, all of which will impact the outcomes of patients undergoing screening for lung cancer., (Copyright © 2023 American College of Chest Physicians. All rights reserved.)

Background: Multiple quality metrics have been recommended to ensure consistent, high-quality execution of screening tests for breast, cervical, colorectal, and lung cancers. However, minimal data exist evaluating the evidence base supporting these recommendations and the consistency of definitions and concepts included within and between cancer types., Methods: We performed a systematic review for each cancer type using MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 2010 to April 2020 to identify guidelines from screening programs or professional organizations containing quality metrics for tests used in breast, cervical, colorectal, and lung cancer screening. We abstracted metrics' definitions, target performance levels, and related supporting evidence for test completeness, adequacy (sufficient visualization or collection), accuracy, and safety., Results: We identified 11 relevant guidelines with 20 suggested quality metrics for breast cancer, 5 guidelines with 9 metrics for cervical cancer, 13 guidelines with 18 metrics for colorectal cancer (CRC), and 3 guidelines with 7 metrics for lung cancer. These included 54 metrics related to adequacy (n = 6), test completeness (n = 3), accuracy (n = 33), and safety (n = 12). Target performance levels were defined for 30 metrics (56%). Ten (19%) were supported by evidence, all from breast and CRC, with no evidence cited to support metrics from cervical and lung cancer screening., Conclusions: Considerably more guideline-recommended test performance metrics exist for breast and CRC screening than cervical or lung cancer. The domains covered are inconsistent among cancers, and few targets are supported by evidence. Clearer evidence-based domains and targets are needed for test performance metrics., Registration: PROSPERO 2020 CRD42020179139., (© The Author(s) 2023. Published by Oxford University Press.)

Competing Interests: The authors report no conflicts of interest.

Background: Cancer screening should be recommended only when the balance between benefits and harms is favorable. This review evaluated how U.S. cancer screening guidelines reported harms, within and across organ-specific processes to screen for cancer., Objective: To describe current reporting practices and identify opportunities for improvement., Design: Review of guidelines., Setting: United States., Patients: Patients eligible for screening for breast, cervical, colorectal, lung, or prostate cancer according to U.S. guidelines., Measurements: Information was abstracted on reporting of patient-level harms associated with screening, diagnostic follow-up, and treatment. The authors classified harms reporting as not mentioned, conceptual, qualitative, or quantitative and noted whether literature was cited when harms were described. Frequency of harms reporting was summarized by organ type., Results: Harms reporting was inconsistent across organ types and at each step of the cancer screening process. Guidelines did not report all harms for any specific organ type or for any category of harm across organ types. The most complete harms reporting was for prostate cancer screening guidelines and the least complete for colorectal cancer screening guidelines. Conceptualization of harms and use of quantitative evidence also differed by organ type., Limitations: This review considers only patient-level harms. The authors did not verify accuracy of harms information presented in the guidelines., Conclusion: The review identified opportunities for improving conceptualization, assessment, and reporting of screening process-related harms in guidelines. Future work should consider nuances associated with each organ-specific process to screen for cancer, including which harms are most salient and where evidence gaps exist, and explicitly explore how to optimally weigh available evidence in determining net screening benefit. Improved harms reporting could aid informed decision making, ultimately improving cancer screening delivery., Primary Funding Source: National Cancer Institute.

Background: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was recommended by the U.S. Preventive Services Task Force (USPSTF) in 2013, making approximately 8 million Americans eligible for screening. The demographic characteristics and adherence of persons screened in the United States have not been reported at the population level., Objective: To define sociodemographic characteristics and adherence among persons screened and entered into the American College of Radiology's Lung Cancer Screening Registry (LCSR)., Design: Cohort study., Setting: United States, 2015 to 2019., Participants: Persons receiving a baseline LDCT for LCS from 3625 facilities reporting to the LCSR., Measurements: Age, sex, and smoking status distributions (percentages) were computed among persons who were screened and among respondents in the 2015 National Health Interview Survey (NHIS) who were eligible for screening. The prevalence between the LCSR and the NHIS was compared with prevalence ratios (PRs) and 95% CIs. Adherence to annual screening was defined as having a follow-up test within 11 to 15 months of an initial LDCT., Results: Among 1 159 092 persons who were screened, 90.8% ( n = 1 052 591) met the USPSTF eligibility criteria. Compared with adults from the NHIS who met the criteria ( n = 1257), screening recipients in the LCSR were older (34.7% vs. 44.8% were aged 65 to 74 years; PR, 1.29 [95% CI, 1.20 to 1.39]), more likely to be female (41.8% vs. 48.1%; PR, 1.15 [CI, 1.08 to 1.23]), and more likely to currently smoke (52.3% vs. 61.4%; PR, 1.17 [CI, 1.11 to 1.23]). Only 22.3% had a repeated annual LDCT. If follow-up was extended to 24 months and more than 24 months, 34.3% and 40.3% were adherent, respectively., Limitations: Underreporting of LCS and missing data may skew demographic characteristics of persons reported to be screened. Underreporting of adherence may result in underestimates of follow-up., Conclusion: Approximately 91% of persons who had LCS met USPSTF eligibility criteria. In addition to continuing to target all eligible adults, men, those who formerly smoked, and younger eligible patients may be less likely to be screened. Adherence to annual follow-up screening was poor, potentially limiting screening effectiveness., Primary Funding Source: None.

Background: Cancer screening is a complex process involving multiple steps and levels of influence (e.g., patient, provider, facility, health care system, community, or neighborhood). We describe the design, methods, and research agenda of the Population-based Research to Optimize the Screening Process (PROSPR II) consortium. PROSPR II Research Centers (PRC), and the Coordinating Center aim to identify opportunities to improve screening processes and reduce disparities through investigation of factors affecting cervical, colorectal, and lung cancer screening in U.S. community health care settings., Methods: We collected multilevel, longitudinal cervical, colorectal, and lung cancer screening process data from clinical and administrative sources on &gt;9 million racially and ethnically diverse individuals across 10 heterogeneous health care systems with cohorts beginning January 1, 2010. To facilitate comparisons across organ types and highlight data breadth, we calculated frequencies of multilevel characteristics and volumes of screening and diagnostic tests/procedures and abnormalities., Results: Variations in patient, provider, and facility characteristics reflected the PROSPR II health care systems and differing target populations. PRCs identified incident diagnoses of invasive cancers, in situ cancers, and precancers (invasive: 372 cervical, 24,131 colorectal, 11,205 lung; in situ: 911 colorectal, 32 lung; precancers: 13,838 cervical, 554,499 colorectal)., Conclusions: PROSPR II's research agenda aims to advance: (i) conceptualization and measurement of the cancer screening process, its multilevel factors, and quality; (ii) knowledge of cancer disparities; and (iii) evaluation of the COVID-19 pandemic's initial impacts on cancer screening. We invite researchers to collaborate with PROSPR II investigators., Impact: PROSPR II is a valuable data resource for cancer screening researchers., (©2022 American Association for Cancer Research.)

With increased attention to the financing and structure of healthcare, dramatic increases in the cost of diagnosing and treating cancer, and corresponding disparities in access, the study of healthcare economics and delivery has become increasingly important. The Healthcare Delivery Research Program (HDRP) in the Division of Cancer Control and Population Sciences at the National Cancer Institute (NCI) was formed in 2015 to provide a hub for cancer-related healthcare delivery and economics research. However, the roots of this program trace back much farther, at least to the formation of the NCI Division of Cancer Prevention and Control in 1983. The creation of a division focused on understanding and explaining trends in cancer morbidity and mortality was instrumental in setting the direction of cancer-related healthcare delivery and health economics research over the subsequent decades. In this commentary, we provide a brief history of health economics and healthcare delivery research at NCI, describing the organizational structure and highlighting key initiatives developed by the division, and also briefly discuss future directions. HDRP and its predecessors have supported the growth and evolution of these fields through the funding of grants and contracts; the development of data, tools, and other research resources; and thought leadership including stimulation of research on previously understudied topics. As the availability of new data, methods, and computing capacity to evaluate cancer-related healthcare delivery and economics expand, HDRP aims to continue to support this growth and evolution., (Published by Oxford University Press 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Purpose: To determine whether military men report different prostate-specific antigen (PSA) screening rates than civilian men and if shared decision-making (SDM) is associated with PSA screening., Methods: We used data from the 2018 Behavioral Risk Factor Surveillance System and included 101,901 men (26,363 military and 75,538 civilian men) in the analysis conducted in 2021. We conducted binomial logistic regression analyses to determine covariate-adjusted associations between military status and receiving a PSA test in the last 2 years. We then added patient reports of SDM to the model. Finally, we looked at the joint effects of military status and SDM on the receipt of a PSA test in the last 2 years., Results: Military men had 1.1 times the odds of PSA testing compared to civilian men (95% CI 1.1, 1.2) after adjusting for SDM and sociodemographic and health covariates. When examining the joint effect of military status and SDM, military and civilian men had over three times the odds of receiving a PSA test in the last 2 years if they had reported SDM (OR 3.5 and OR 3.4, respectively) compared to civilian men who did not experience SDM., Conclusion: Military men are slightly more likely to report receiving a PSA test in the last 2 years compared to civilian men. Additionally, results show SDM plays a role in the receipt of a PSA test in both populations. These findings can serve as a foundation for tailored interventions to promote appropriate SDM for PSA screening in civilian, active duty, and veteran healthcare systems., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Improvements in cancer care delivery have the potential to reduce morbidity and mortality from cancer, however, challenges to delivery of recommended care limit progress. These challenges include growing demands for care, increasing treatment complexity, inadequate care coordination, dramatic increases in costs, persistent disparities in care, and insufficient use of evidence-based guidelines. Recognizing the important role of research in understanding and addressing these challenges, the National Cancer Institute created the Healthcare Delivery Research Program (HDRP) in 2015 as a catalyst for expanding work in this area. Health-care delivery research is a multidisciplinary effort which recognizes that care delivery occurs in a multilevel system encompassing individuals, health-care systems, and communities. HDRP staff use a range of activities to fulfill the program's mission of advancing innovative research to improve delivery of care across the cancer control continuum. In addition to developing funding opportunities, HDRP staff; support and facilitate the use of research infrastructure for conducting health-care delivery research; oversee publicly available data that can be used to evaluate patterns, costs, and patient experiences of care; contribute to development and dissemination of standardized health measurement tools for public use; and support professional development and training to build capacity within the field and grow the workforce. As HDRP enters its sixth year, we appreciate the opportunity to reflect on the program's progress in advancing the science of health-care delivery. At the same time, we recognize the need for the program to evolve and develop additional resources and opportunities to address new and emerging challenges., (Published by Oxford University Press 2021. This work is written by US Government employees and is in the public domain in the US.)

Background: It is strongly recommended that adults aged 50-75 years be screened for colorectal cancer. Recommended screening options include colonoscopy, sigmoidoscopy, CT colonography, guaiac fecal occult blood testing (FOBT), fecal immunochemical testing (FIT), or the more recently introduced FIT-DNA (FIT in combination with a stool DNA test). Colorectal cancer screening programs can benefit from knowledge of patterns of use by test type and within population subgroups., Methods: Using 2018 National Health Interview Survey (NHIS) data, we examined colorectal cancer screening test use for adults aged 50-75 years ( N = 10,595). We also examined time trends in colorectal cancer screening test use from 2010-2018., Results: In 2018, an estimated 66.9% of U.S. adults aged 50-75 years had a colorectal cancer screening test within recommended time intervals. However, the prevalence was less than 50% among those aged 50-54 years, those without a usual source of health care, those with no doctor visits in the past year, and those who were uninsured. The test types most commonly used within recommended time intervals were colonoscopy within 10 years (61.1%), FOBT or FIT in the past year (8.8%), and FIT-DNA within 3 years (2.7%). After age-standardization to the 2010 census population, the percentage up-to-date with CRC screening increased from 61.2% in 2015 to 65.3% in 2018, driven by increased use of stool testing, including FIT-DNA., Conclusions: These results show some progress, driven by a modest increase in stool testing. However, colorectal cancer testing remains low in many population subgroups., Impact: These results can inform efforts to achieve population colorectal cancer screening goals., (©2021 American Association for Cancer Research.)

The success of fecal occult blood-based colorectal cancer screening programs is dependent on repeating screening at short intervals (ie, every 1-2 years). We conducted a literature review to assess measures that have been used to assess longitudinal adherence to fecal-based screening. Among 46 citations identified and included in this review, six broad classifications of longitudinal adherence were identified: (a) stratified single-round attendance, (b) all possible adherence permutations, (c) consistent/inconsistent/never attendance, (d) number of times attended, (e) program adherence and (f) proportion of time covered. Advantages and disadvantages of these measures are described, and recommendations on which measures to use based on data availability and scientific question are also given. Stratified single round attendance is particularly useful for describing the yield of screening, while programmatic adherence measures are best suited to evaluating screening efficacy. We recommend that screening programs collect detailed longitudinal, individual-level data, not only for the screening tests themselves but additionally for diagnostic follow-up and surveillance exams, to allow for maximum flexibility in reporting adherence patterns using the measure of choice., (© 2021 UICC.)

Objective: To examine whether receiving a fecal occult blood test after a negative sigmoidoscopy reduced mortality from colorectal cancer., Methods: We used a nested case-control design with incidence-density matching in historical cohorts of 1,877,740 50-90-year-old persons during 2006-2012, in an integrated health-system setting. We selected 1758 average risk patients who died from colorectal cancer and 3503 matched colorectal cancer-free persons. Colorectal cancer-specific death was ascertained from cancer and mortality registries. Screening histories were determined from electronic and chart-audit clinical data in the 5- to 10-year period prior to the reference date. We evaluated receipt of subsequent fecal occult blood test within five years of the reference date among patients with negative sigmoidoscopy two to six years before the reference date., Results: Of the 5261 patients, 831 patients (204 colorectal cancer deaths/627 controls) had either negative sigmoidoscopy only ( n  = 592) or negative sigmoidoscopy with subsequent screening fecal occult blood test ( n  = 239). Fifty-six (27.5%) of the 204 patients dying of colorectal cancer and 183 (29.2%) of the 627 colorectal cancer-free patients received fecal occult blood test following a negative sigmoidoscopy. Conditional regressions found no significant association between fecal occult blood test receipt and colorectal cancer death risk, overall (adjusted odds ratio = 0.93, confidence interval: 0.65-1.33), or for right (odds ratio = 1.02, confidence interval: 0.65-1.60) or left-colon/rectum (odds ratio = 0.77, confidence interval: 0.39-1.52) cancers. Similar results were obtained in sensitivity analyses with alternative exposure ascertainment windows or timing of fecal occult blood test., Conclusions: Our results suggest that receipt of at least one fecal occult blood test during the several years after a negative sigmoidoscopy did not substantially reduce mortality from colorectal cancer.

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2016 colorectal cancer screening recommendations., Objective: To provide updated model-based estimates of the benefits, burden, and harms of colorectal cancer screening strategies and to identify strategies that may provide an efficient balance of life-years gained (LYG) from screening and colonoscopy burden to inform the USPSTF., Design, Setting, and Participants: Comparative modeling study using 3 microsimulation models of colorectal cancer screening in a hypothetical cohort of 40-year-old US individuals at average risk of colorectal cancer., Exposures: Screening from ages 45, 50, or 55 years to ages 70, 75, 80, or 85 years with fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy alone or with FIT, computed tomography colonography, or colonoscopy. All persons with an abnormal noncolonoscopy screening test result were assumed to undergo follow-up colonoscopy. Screening intervals varied by test. Full adherence with all procedures was assumed., Main Outcome and Measures: Estimated LYG relative to no screening (benefit), lifetime number of colonoscopies (burden), number of complications from screening (harms), and balance of incremental burden and benefit (efficiency ratios). Efficient strategies were those estimated to require fewer additional colonoscopies per additional LYG relative to other strategies., Results: Estimated LYG from screening strategies ranged from 171 to 381 per 1000 40-year-olds. Lifetime colonoscopy burden ranged from 624 to 6817 per 1000 individuals, and screening complications ranged from 5 to 22 per 1000 individuals. Among the 49 strategies that were efficient options with all 3 models, 41 specified screening beginning at age 45. No single age to end screening was predominant among the efficient strategies, although the additional LYG from continuing screening after age 75 were generally small. With the exception of a 5-year interval for computed tomography colonography, no screening interval predominated among the efficient strategies for each modality. Among the strategies highlighted in the 2016 USPSTF recommendation, lowering the age to begin screening from 50 to 45 years was estimated to result in 22 to 27 additional LYG, 161 to 784 additional colonoscopies, and 0.1 to 2 additional complications per 1000 persons (ranges are across screening strategies, based on mean estimates across models). Assuming full adherence, screening outcomes and efficient strategies were similar by sex and race and across 3 scenarios for population risk of colorectal cancer., Conclusions and Relevance: This microsimulation modeling analysis suggests that screening for colorectal cancer with stool tests, endoscopic tests, or computed tomography colonography starting at age 45 years provides an efficient balance of colonoscopy burden and life-years gained.

Screening for breast cancer, cervical cancer, and colorectal cancer (CRC) reduces mortality from these cancers.* However, screening test receipt has been below national targets with disparities observed in certain populations (1,2). National Health Interview Survey (NHIS) data from 2018 were analyzed to estimate percentages of adults up to date with U.S. Preventive Services Task Force (USPSTF) screening recommendations. Screening test receipt remained below national Healthy People 2020 (HP2020) targets, although CRC test receipt neared the target. Disparities were evident, with particularly low test receipt among persons who were uninsured or did not have usual sources of care. Continued monitoring helps assess progress toward targets and could inform efforts to promote screening and reduce barriers for underserved populations., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Colonoscopy follow-up recommendations depend on the presence or absence of polyps, and if found, their number, size, and histology. Patients may be responsible for conveying results between primary and specialty care or providing medical information to family members; thus, accurate reporting is critical. This analysis assessed the accuracy of self-reported colonoscopy findings., Methods: 3,986 participants from the Study of Colonoscopy Utilization, an ancillary study nested within the Prostate, Lung, Colorectal, and Ovarian Screening Trial, were included. Self-reports of polyp and adenoma were compared to medical records, and measures of sensitivity and specificity were calculated. Correlates of accurate self-report of polyp were assessed using logistic regression and weighted to account for study sampling., Results: The sensitivity and specificity of self-reported polyp findings were 88% and 85%, respectively, and for adenoma 11% and 99%, respectively. Among participants with a polyp, older age was associated with lower likelihood while polyp severity and non-white race were associated with increased likelihood of accurate recall. Among participants without a polyp, having multiple colonoscopies was associated with lower likelihood while family history of colorectal cancer was associated with increased likelihood of accurate recall. Among both groups, longer time since colonoscopy was associated with lower likelihood of accurate recall., Conclusions: Participants recalled with reasonable accuracy whether they had a prior polyp; however, recall of histology, specifically adenoma, was much less accurate., Impact: Identification of strategies to increase accurate self-report of colonic polyps are needed, particularly for patient-provider communications and patient reporting of results to family members., (©2020 American Association for Cancer Research.)

Background: Cancer screening is a complex process encompassing risk assessment, the initial screening examination, diagnostic evaluation, and treatment of cancer precursors or early cancers. Metrics that enable comparisons across different screening targets are needed. We present population-based screening metrics for breast, cervical, and colorectal cancers for nine sites participating in the Population-based Research Optimizing Screening through Personalized Regimens consortium., Methods: We describe how selected metrics map to a trans-organ conceptual model of the screening process. For each cancer type, we calculated calendar year 2013 metrics for the screen-eligible target population (breast: ages 40-74 years; cervical: ages 21-64 years; colorectal: ages 50-75 years). Metrics for screening participation, timely diagnostic evaluation, and diagnosed cancers in the screened and total populations are presented for the total eligible population and stratified by age group and cancer type., Results: The overall screening-eligible populations in 2013 were 305 568 participants for breast, 3 160 128 for cervical, and 2 363 922 for colorectal cancer screening. Being up-to-date for testing was common for all three cancer types: breast (63.5%), cervical (84.6%), and colorectal (77.5%). The percentage of abnormal screens ranged from 10.7% for breast, 4.4% for cervical, and 4.5% for colorectal cancer screening. Abnormal breast screens were followed up diagnostically in almost all (96.8%) cases, and cervical and colorectal were similar (76.2% and 76.3%, respectively). Cancer rates per 1000 screens were 5.66, 0.17, and 1.46 for breast, cervical, and colorectal cancer, respectively., Conclusions: Comprehensive assessment of metrics by the Population-based Research Optimizing Screening through Personalized Regimens consortium enabled systematic identification of screening process steps in need of improvement. We encourage widespread use of common metrics to allow interventions to be tested across cancer types and health-care settings., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Numerous organizations, including the United States Preventive Services Task Force, recommend annual lung cancer screening (LCS) with low-dose CT for high risk adults who meet specific criteria. Despite recommendations and national coverage for screening eligible adults through the Centers for Medicare and Medicaid Services, LCS uptake in the United States remains low (<4%). In recognition of the need to improve and understand LCS across the population, as part of the larger Population-based Research to Optimize the Screening PRocess (PROSPR) consortium, the NCI (Bethesda, MD) funded the Lung PROSPR Research Consortium consisting of five diverse healthcare systems in Colorado, Hawaii, Michigan, Pennsylvania, and Wisconsin. Using various methods and data sources, the center aims to examine utilization and outcomes of LCS across diverse populations, and assess how variations in the implementation of LCS programs shape outcomes across the screening process. This commentary presents the PROSPR LCS process model, which outlines the interrelated steps needed to complete the screening process from risk assessment to treatment. In addition to guiding planned projects within the Lung PROSPR Research Consortium, this model provides insights on the complex steps needed to implement, evaluate, and improve LCS outcomes in community practice., (©2019 American Association for Cancer Research.)

Background: Flexible sigmoidoscopy and colonoscopy are both recommended colorectal cancer screening options, but their relative effectiveness needs clarification. The aim of this study was to compare the effectiveness of colonoscopy and flexible sigmoidoscopy for reduction of colorectal cancer incidence., Methods: We conducted a case-control study within the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Cases were subjects age 70-85 years in the SEER-Medicare database diagnosed with CRC during 2004-2013. Up to 3 controls were matched to each case by birth year, sex, race, and SEER region. Receipt of screening colonoscopy or flexible sigmoidoscopy was ascertained from Medicare claims. Conditional logistic regression models were developed to estimate the odds ratios (ORs) and 95% confidence intervals (CI) for a history of screening in cases vs. controls. We conducted secondary analyses by sex, race, endoscopist characteristics, and with varying timing and duration of the look-back period., Results: Receipt of screening colonoscopy and sigmoidoscopy was associated with a 59% (OR 0.41, 95%CI 0.39, 0.43) and 22% reduction (OR 0.78, 95%CI 0.67, 0.92) in colorectal cancer incidence, respectively. Colonoscopy was associated with greater reduction in the distal colorectal cancer incidence (OR 0.22, 95%CI 0.20, 0.24) than proximal colorectal cancer incidence (OR 0.62, 95%CI 0.59, 0.66). Sigmoidoscopy was associated with a 52% reduction in distal colorectal cancer incidence (OR 0.48, 95%CI 0.37, 0.63), but with no reduction in proximal colorectal cancer incidence. These associations were stronger in men than in women. No differences by race or endoscopist characteristics were observed., Conclusion: Both screening colonoscopy and sigmoidoscopy were associated with reductions in overall colorectal cancer incidence, with a greater magnitude of reduction observed with colonoscopy., Competing Interests: Michael J. Barrett is an employee of Information Management Systems, Inc., the information technology contractor of the National Cancer Institute. This company assists researchers with creation of SEER-Medicare data files and assistance with data analyses, and does not have a commercial interest in any products or publications resulting from this database. This commercial affiliation does not alter adherence to all PLOS ONE policies on sharing data and materials.

Background: Despite the importance of characterizing colonoscopy indication for quality monitoring and cancer screening program evaluation, there is no standard approach to documenting colonoscopy indication in medical records., Methods: We applied two algorithms in three health care systems to assign colonoscopy indication to persons 50-89 years old who received a colonoscopy during 2010-2013. Both algorithms used standard procedure, diagnostic, and laboratory codes. One algorithm, the KPNC algorithm, used a hierarchical approach to classify exam indication into: diagnostic, surveillance, or screening; whereas the other, the SEARCH algorithm, used a logistic regression-based algorithm to provide the probability that colonoscopy was performed for screening. Gold standard assessment of indication was from medical records abstraction., Results: There were 1,796 colonoscopy exams included in analyses; age and racial/ethnic distributions of participants differed across health care systems. The KPNC algorithm's sensitivities and specificities for screening indication ranged from 0.78-0.82 and 0.78-0.91, respectively; sensitivities and specificities for diagnostic indication ranged from 0.78-0.89 and 0.74-0.82, respectively. The KPNC algorithm had poor sensitivities (ranging from 0.11-0.67) and high specificities for surveillance exams. The Area Under the Curve (AUC) of the SEARCH algorithm for screening indication ranged from 0.76-0.84 across health care systems. For screening indication, the KPNC algorithm obtained higher specificities than the SEARCH algorithm at the same sensitivity., Conclusion: Despite standardized implementation of these indication algorithms across three health care systems, the capture of colonoscopy indication data was imperfect. Thus, we recommend that standard, systematic documentation of colonoscopy indication should be added to medical records to ensure efficient and accurate data capture., Competing Interests: The authors have no competing interests to declare.

Purpose: Colonoscopy and flexible sigmoidoscopy are both recommended colorectal cancer (CRC) screening strategies, but their relative effectiveness is unclear. We sought to evaluate the ability of each of these two modalities to reduce CRC mortality., Methods: We conducted a case-control study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Cases were persons aged 70-85 years who died of CRC and were matched to up to three non-CRC controls. Receipt of endoscopy was ascertained from Medicare claims and endoscopy indication assigned using a validated algorithm. Conditional logistic regression models were developed to estimate the association between screening colonoscopy or sigmoidoscopy and CRC mortality. We conducted secondary analyses by race, sex, and endoscopist characteristics, and with varying duration of the look-back period., Results: In the initial analysis using all available look-back years, screening flexible sigmoidoscopy was associated with a 35% reduction in CRC mortality (OR 0.65, 95% CI 0.48, 0.89), while screening colonoscopy was associated with a 74% reduction (OR 0.26, 95% CI 0.23, 0.30). Sigmoidoscopy was not associated with any reduction in proximal CRC mortality. The association between colonoscopy and reduced CRC mortality was stronger in the distal than the proximal colon. Results were similar in analyses using a 5-year look-back period., Conclusions: Screening colonoscopy was associated with greater reductions in CRC mortality than screening sigmoidoscopy, and with a greater reduction in the distal than the proximal colon. These results provide additional information on the relative benefits of screening for CRC with sigmoidoscopy and colonoscopy.

Case-control studies evaluating a screening test's efficacy in reducing cancer mortality require accurate classification of test indication to obtain a valid result. However, for analogous studies of cancer incidence, determination of test indication is not as critical because, to define exposure, we need consider only tests that can identify precursor lesions whose treatment might prevent cancer, not tests leading to cancer diagnosis. This study utilizes US Surveillance, Epidemiology, and End Results (SEER)-Medicare data, which do not include information about colonoscopy indication, to evaluate the efficacy of colonoscopy in preventing colorectal cancer (CRC) incidence. Cases were Medicare enrollees diagnosed with CRC between 1996 and 2013; up to 3 controls were matched to each case. Colonoscopy receipt prior to presumed onset of occult cancer was associated with an approximately 60% reduction in CRC incidence (odds ratio = 0.41, 95% confidence interval: 0.40, 0.42). The association was robust to differing exposure windows and estimates of occult cancer duration and is similar to those from CRC incidence studies in which exam indication was available. Our results suggest that, when it is impractical/impossible to determine whether tests were conducted for screening, the efficacy of a test in preventing cancer incidence can still be estimated using a case-control study design., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019.)

The National Lung Screening Trial (NLST) reported substantial reduction in lung cancer mortality among high-risk individuals screened annually with low-dose helical computed tomography (LDCT). As a result, the US Preventive Services Task Force issued a B recommendation for annual LDCT in high-risk individuals, which requires private insurers to cover it without cost-sharing. The Medicare program also covers LDCT for high-risk beneficiaries without cost-sharing. However, the NLST findings may not be generalizable to the community setting because of differences in patients, providers, and practices participating in the NLST. Thus, examining uptake of LDCT screening in community practice is critical, as is evaluating the immediate and downstream outcomes of screening, including false-positive scans, follow-up examinations and adverse events, costs, stage of disease at diagnosis, and survival. This commentary presents an overview of the landscape of the data resources currently available to evaluate the uptake, outcomes, and costs of LDCT screening in the United States. We describe the strengths and limitations of existing data sources, including administrative databases, surveys, and registries. Thereafter, we provide recommendations for improving the data infrastructure pertaining to three overarching research areas: receipt of guideline-consistent screening and follow-up, weighing benefits and harms of screening, and costs of screening., (Published by Oxford University Press 2019.)

The Cancer Research Network (CRN) is a consortium of 12 research groups, each affiliated with a nonprofit integrated health care delivery system, that was first funded in 1998. The overall goal of the CRN is to support and facilitate collaborative cancer research within its component delivery systems. This paper describes the CRN's 20-year experience and evolution. The network combined its members' scientific capabilities and data resources to create an infrastructure that has ultimately supported over 275 projects. Insights about the strengths and limitations of electronic health data for research, approaches to optimizing multidisciplinary collaboration, and the role of a health services research infrastructure to complement traditional clinical trials and large observational datasets are described, along with recommendations for other research consortia., Competing Interests: The authors have no competing interests to declare.

Background: To reduce colorectal cancer incidence and mortality, experts recommend surveillance colonoscopy 3 years after advanced adenoma removal. Little is known about adherence to that interval., Methods: We describe patterns of and factors associated with subsequent colonoscopy among persons with ≥3 adenomas and/or ≥1 adenoma with villous/tubulovillous histology in four U.S. integrated healthcare delivery systems. We report Kaplan-Meier estimators of the cumulative percentage of patients undergoing colonoscopy 6 months to 3.5 years after an index colonoscopy with high-risk findings. Combining data from three healthcare systems, we used multivariable logistic regression with inverse probability of censoring weights to estimate ORs and 95% confidence intervals (CI) for associations between patient characteristics and receipt of subsequent colonoscopy., Results: Among 6,909 persons with advanced adenomas, the percent receiving a subsequent colonoscopy 6 months to 3.5 years later ranged from 18.3% (95% CI: 11.7%-27.8%) to 59.5% (95% CI: 53.8%-65.2%) across healthcare systems. Differences remained significant in the multivariable model. Patients with ≥3 adenomas were more likely than those with 1 to 2 villous/tubulovillous adenomas to undergo subsequent colonoscopy. Subsequent colonoscopy was also more common for patients ages 60-74 and less common for patients ages 80 to 89 compared with those ages 50 to 54 years at their index colonoscopy. Sex, race/ethnicity, and comorbidity index score were generally not associated with subsequent colonoscopy receipt., Conclusions: Colonoscopy within the recommended interval following advanced adenoma was underutilized and varied by healthcare system, age, and number of adenomas., Impact: Strategies to improve adherence to surveillance colonoscopy following advanced adenomas are needed., (©2018 American Association for Cancer Research.)

Introduction: Prior studies suggest overuse of nonrecommended lung cancer screening tests in U.S. community practice and underuse of recommended tests., Methods: Data from the 2010 and 2015 National Health Interview Surveys was analyzed from 2016 to 2018. Prevalence, populations, and number of chest computed tomography (CT) and chest x-ray tests were estimated for people who did and did not meet U.S. Preventive Services Task Force (USPSTF) criteria for lung cancer screening, among people aged ≥40 years without lung cancer., Results: In 2015, among those who met USPSTF criteria, 4.4% (95% CI=3.0%, 6.6%), or 360,000 (95% CI=240,000, 535,000) people reported lung cancer screening with a chest CT; and 8.5% (95% CI=6.5%, 11.1%), or 689,000 (95% CI=526,000, 898,000) people reported a chest x ray. Among those who did not meet USPSTF criteria, 2.3% (95% CI=2.0%, 2.6%), or 3,259,000 (95% CI=2,850,000, 3,724,000) people reported a chest x ray; and 1.3% (95% CI=1.1%, 1.5%), or 1,806,000 (95% CI=1,495,000, 2,173,000) people reported a chest CT. The estimated population meeting USPSTF criteria for lung cancer screening in 2015 was 8,098,000 (95% CI=7,533,000, 8,702,000), which was smaller than the 9,620,000 people (95% CI=8,960,000, 10,325,000) in 2010., Conclusions: The number of adults inappropriately screened for lung cancer greatly exceeds the number screened according to USPSTF recommendations, the prevalence of appropriate lung cancer screening is low, and the population meeting USPSTF criteria is shrinking. To realize the potential benefits of screening, better processes to appropriately triage eligible individuals to screening, plus screening with a USPSTF-recommended test, would be beneficial., (Published by Elsevier Inc.)

Objective: Screening colonoscopy's effectiveness in reducing colorectal cancer mortality risk in community populations is unclear, particularly for right-colon cancers, leading to recommendations against its use for screening in some countries. This study aimed to determine whether, among average-risk people, receipt of screening colonoscopy reduces the risk of dying from both right-colon and left-colon/rectal cancers., Design: We conducted a nested case-control study with incidence-density matching in screening-eligible Kaiser Permanente members. Patients who were 55-90 years old on their colorectal cancer death date during 2006-2012 were matched on diagnosis (reference) date to controls on age, sex, health plan enrolment duration and geographical region. We excluded patients at increased colorectal cancer risk, or with prior colorectal cancer diagnosis or colectomy. The association between screening colonoscopy receipt in the 10-year period before the reference date and colorectal cancer death risk was evaluated while accounting for other screening exposures., Results: We analysed 1747 patients who died from colorectal cancer and 3460 colorectal cancer-free controls. Compared with no endoscopic screening, receipt of a screening colonoscopy was associated with a 67% reduction in the risk of death from any colorectal cancer (adjusted OR (aOR)=0.33, 95% CI 0.21 to 0.52). By cancer location, screening colonoscopy was associated with a 65% reduction in risk of death for right-colon cancers (aOR=0.35, CI 0.18 to 0.65) and a 75% reduction for left-colon/rectal cancers (aOR=0.25, CI 0.12 to 0.53)., Conclusions: Screening colonoscopy was associated with a substantial and comparably decreased mortality risk for both right-sided and left-sided cancers within a large community-based population., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Rationale: Lung cancer screening registries can monitor screening outcomes and improve quality of care., Objectives: To describe nascent lung cancer screening programs and share efficient data collection approaches for mandatory registry reporting in four integrated health care systems of the National Cancer Institute-funded Cancer Research Network., Methods: We documented the distinctive characteristics of lung cancer screening programs, and we provide examples of strategies to facilitate data collection and describe early challenges and possible solutions. In addition, we report preliminary data on use and outcomes of screening with low-dose computed tomography at each of the participating sites., Results: Programs varied in approaches to confirming patient eligibility, ordering screening low-dose computed tomographic scans, and coordinating follow-up care. Most data elements were collected from structured fields in electronic health records, but sites also made use of standardized order templates, local procedure codes, identifiable hashtags in radiology reports, and natural language processing algorithms. Common challenges included incomplete documentation of tobacco smoking history, difficulty distinguishing between scans performed for screening versus diagnosis or surveillance, and variable adherence with use of standardized templates. Adherence with eligibility criteria as well as the accuracy and completeness of data collection appeared to depend at least partly on availability of personnel and other resources to support the successful implementation of screening., Conclusions: To maximize the effectiveness of lung cancer screening, minimize the burden of data collection, and facilitate research and quality improvement, clinical workflow and information technology should be purposefully designed to ensure that patients meet eligibility criteria and receive appropriate follow-up testing.

Expanding research capacity of large research networks within health care delivery systems requires strategically training both embedded and external investigators in necessary skills for this purpose. Researchers new to these settings frequently lack the skills and specialized knowledge conducive to multi-site and multi-disciplinary research set in delivery systems. This report describes the goals and components of the Cancer Research Network (CRN) Scholars Program, a 26-month training program developed to increase the capacity for cancer research conducted within the network's participating sites, its progression from training embedded investigators to a mix of internal and external investigators, and the content evolution of the training program. The CRN Scholars program was launched in 2007 to assist junior investigators from member sites develop independent and sustainable research programs within the CRN. Resulting from CRN's increased emphasis on promoting external collaborations, the 2013 Scholars program began recruiting junior investigators from external institutions committed to conducting delivery system science. Based on involvement of this broader population and feedback from prior Scholar cohorts, the program has honed its focus on specific opportunities and issues encountered in conducting cancer research within health care delivery systems. Efficiency and effectiveness of working within networks is accelerated by strategic and mentored navigation of these networks. Investing in training programs specific to these settings provides the opportunity to improve multi-disciplinary and multi-institutional collaboration, particularly for early-stage investigators. Aspects of the CRN Scholars Program may help inform others considering developing similar programs to expand delivery system research or within large, multi-disciplinary research networks.

Precision medicine, an emerging approach for disease treatment that takes into account individual variability in genes, environment, and lifestyle, is under consideration for preventive interventions, including cancer screening. On September 29, 2015, the National Cancer Institute sponsored a symposium entitled "Precision Cancer Screening in the General Population: Evidence, Epidemiology, and Next Steps". The goal was two-fold: to share current information on the evidence, practices, and challenges surrounding precision screening for breast, cervical, colorectal, lung, and prostate cancers, and to allow for in-depth discussion among experts in relevant fields regarding how epidemiology and other population sciences can be used to generate evidence to inform precision screening strategies. Attendees concluded that the strength of evidence for efficacy and effectiveness of precision strategies varies by cancer site, that no one research strategy or methodology would be able or appropriate to address the many knowledge gaps in precision screening, and that issues surrounding implementation must be researched as well. Additional discussion needs to occur to identify the high priority research areas in precision cancer screening for pertinent organs and to gather the necessary evidence to determine whether further implementation of precision cancer screening strategies in the general population would be feasible and beneficial. Cancer Epidemiol Biomarkers Prev; 25(11); 1449-55. ©2016 AACR., Competing Interests: of Potential Conflicts of Interest M.K. Gould reports receiving other commercial support from Archimedes. No potential conflicts of interest were disclosed by the other authors., (©2016 American Association for Cancer Research.)

Purpose: The ability to collect data on patients for long periods prior to, during, and after a cancer diagnosis is critical for studies of cancer etiology, prevention, treatment, outcomes, and costs. We describe such data capacities within the Cancer Research Network (CRN), a cooperative agreement between the National Cancer Institute (NCI) and organized health care systems across the United States., Methods: Data were extracted from each CRN site's virtual data warehouse using a centrally written and locally executed program. We computed the percent of patients continuously enrolled ≥1, ≥5, and ≥10 years before cancer diagnosis in 2012-2015 (year varied by CRN site). To describe retention after diagnosis, we computed the cumulative percentages enrolled, deceased, and disenrolled each year after the diagnosis for patients diagnosed in 2000., Results: Approximately 8 million people were enrolled in ten CRN health plans on December 31, 2014 or 2015 (year varied by CRN site). Among more than 30,000 recent cancer diagnoses, 70 % were enrolled for ≥5 years and 56 % for ≥10 years before diagnosis. Among 25,274 cancers diagnosed in 2000, 28 % were still enrolled in 2010, 45 % had died, and 27 % had disenrolled from CRN health systems., Conclusions: Health plan enrollment before cancer diagnosis was generally long in the CRN, and the proportion of patients lost to follow-up after diagnosis was low. With long enrollment histories among cancer patients pre-diagnosis and low post-diagnosis disenrollment, the CRN provides an excellent platform for epidemiologic and health services research on cancer incidence, outcomes, and costs.

Background/aims: Randomized controlled trials frequently use death review committees to assign a cause of death rather than relying on cause of death information from death certificates. The National Lung Screening Trial, a randomized controlled trial of lung cancer screening with low-dose computed tomography versus chest X-ray for heavy and/or long-term smokers ages 55-74 years at enrollment, used a committee blinded to arm assignment for a subset of deaths to determine whether cause of death was due to lung cancer., Methods: Deaths were selected for review using a pre-determined computerized algorithm. The algorithm, which considered cancers diagnosed during the trial, causes and significant conditions listed on the death certificate, and the underlying cause of death derived from death certificate information by trained nosologists, selected deaths that were most likely to represent a death due to lung cancer (either directly or indirectly) and deaths that might have been erroneously assigned lung cancer as the cause of death. The algorithm also selected deaths that might be due to adverse events of diagnostic evaluation for lung cancer. Using the review cause of death as the gold standard and lung cancer cause of death as the outcome of interest (dichotomized as lung cancer versus not lung cancer), we calculated performance measures of the death certificate cause of death. We also recalculated the trial primary endpoint using the death certificate cause of death., Results: In all, 1642 deaths were reviewed and assigned a cause of death (42% of the 3877 National Lung Screening Trial deaths). Sensitivity of death certificate cause of death was 91%; specificity, 97%; positive predictive value, 98%; and negative predictive value, 89%. About 40% of the deaths reclassified to lung cancer cause of death had a death certificate cause of death of a neoplasm other than lung. Using the death certificate cause of death, the lung cancer mortality reduction was 18% (95% confidence interval: 4.2-25.0), as compared with the published finding of 20% (95% confidence interval: 6.7-26.7)., Conclusion: Death review may not be necessary for primary-outcome analyses in lung cancer screening trials. If deemed necessary, researchers should strive to streamline the death review process as much as possible., (© The Author(s) 2016.)

Background: Microsimulation models synthesize evidence about disease processes and interventions, providing a method for predicting long-term benefits and harms of prevention, screening, and treatment strategies. Because models often require assumptions about unobservable processes, assessing a model's predictive accuracy is important., Methods: We validated 3 colorectal cancer (CRC) microsimulation models against outcomes from the United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial, a randomized controlled trial that examined the effectiveness of one-time flexible sigmoidoscopy screening to reduce CRC mortality. The models incorporate different assumptions about the time from adenoma initiation to development of preclinical and symptomatic CRC. Analyses compare model predictions to study estimates across a range of outcomes to provide insight into the accuracy of model assumptions., Results: All 3 models accurately predicted the relative reduction in CRC mortality 10 years after screening (predicted hazard ratios, with 95% percentile intervals: 0.56 [0.44, 0.71], 0.63 [0.51, 0.75], 0.68 [0.53, 0.83]; estimated with 95% confidence interval: 0.56 [0.45, 0.69]). Two models with longer average preclinical duration accurately predicted the relative reduction in 10-year CRC incidence. Two models with longer mean sojourn time accurately predicted the number of screen-detected cancers. All 3 models predicted too many proximal adenomas among patients referred to colonoscopy., Conclusion: Model accuracy can only be established through external validation. Analyses such as these are therefore essential for any decision model. Results supported the assumptions that the average time from adenoma initiation to development of preclinical cancer is long (up to 25 years), and mean sojourn time is close to 4 years, suggesting the window for early detection and intervention by screening is relatively long. Variation in dwell time remains uncertain and could have important clinical and policy implications., (© The Author(s) 2016.)

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2008 colorectal cancer (CRC) screening recommendations., Objective: To inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden., Design, Setting, and Participants: Comparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis., Exposures: Screening with sensitive guaiac-based fecal occult blood testing, fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy with or without stool testing, computed tomographic colonography (CTC), or colonoscopy starting at age 45, 50, or 55 years and ending at age 75, 80, or 85 years. Screening intervals varied by modality. Full adherence for all strategies was assumed., Main Outcomes and Measures: Life-years gained compared with no screening (benefit), lifetime number of colonoscopies required (burden), lifetime number of colonoscopy complications (harms), and ratios of incremental burden and benefit (efficiency ratios) per 1000 40-year-olds., Results: The screening strategies provided LYG in the range of 152 to 313 per 1000 40-year-olds. Lifetime colonoscopy burden per 1000 persons ranged from fewer than 900 (FIT every 3 years from ages 55-75 years) to more than 7500 (colonoscopy screening every 5 years from ages 45-85 years). Harm from screening was at most 23 complications per 1000 persons screened. Strategies with screening beginning at age 50 years generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55 years. There were limited empirical data to support a start age of 45 years. For persons adequately screened up to age 75 years, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50 to 75 years, 4 strategies yielded a comparable balance of screening burden and similar LYG (median LYG per 1000 across the models): colonoscopy every 10 years (270 LYG); sigmoidoscopy every 10 years with annual FIT (256 LYG); CTC every 5 years (248 LYG); and annual FIT (244 LYG)., Conclusions and Relevance: In this microsimulation modeling study of a previously unscreened population undergoing CRC screening that assumed 100% adherence, the strategies of colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, and CTC every 5 years performed from ages 50 through 75 years provided similar LYG and a comparable balance of benefit and screening burden.

Background: Primary care providers and health systems have prominent roles in guiding effective cancer screening., Objective: To characterize variation in screening abnormality rates and timely initial follow-up for common cancer screening tests., Design: Population-based cohort undergoing screening in 2011, 2012, or 2013 at seven research centers comprising the National Cancer Institute-sponsored Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium., Participants: Adults undergoing mammography with or without digital breast tomosynthesis (n = 97,683 ages 40-75 years), fecal occult blood or fecal immunochemical tests (n = 759,553 ages 50-75 years), or Papanicolaou with or without human papillomavirus tests (n = 167,330 ages 21-65 years)., Intervention: Breast, colorectal, or cervical cancer screening., Main Measures: Abnormality rates per 1000 screens; percentage with timely initial follow-up (within 90 days, except 9-month window for BI-RADS 3). Primary care clinic-level variation in percentage with screening abnormality and percentage with timely initial follow-up., Key Results: There were 10,248/97,683 (104.9 per 1000) abnormal breast cancer screens, 35,847/759,553 (47.2 per 1000) FOBT/FIT-positive colorectal cancer screens, and 13,266/167,330 (79.3 per 1000) abnormal cervical cancer screens. The percentage with timely follow-up was 93.2 to 96.7 % for breast centers, 46.8 to 68.7  % for colorectal centers, and 46.6 % for the cervical cancer screening center (low-grade squamous intraepithelial lesions or higher). The primary care clinic variation (25th to 75th percentile) was smaller for the percentage with an abnormal screen (breast, 8.5-10.3 %; colorectal, 3.0-4.8 %; cervical, 6.3-9.9 %) than for the percentage with follow-up within 90 days (breast, 90.2-95.8 %; colorectal, 43.4-52.0 %; cervical, 29.6-61.4 %)., Conclusions: Variation in both the rate of screening abnormalities and their initial follow-up was evident across organ sites and primary care clinics. This highlights an opportunity for improving the delivery of cancer screening through focused study of patient, provider, clinic, and health system characteristics associated with timely follow-up of screening abnormalities., Competing Interests: The authors declare no conflicts of interest. Funders This work was supported by the National Cancer Institute (NCI)-funded Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium (grant numbers U01CA163304 to M.T., W.B.; U54CA163303 to D.L.W., B.S.; U54CA163307 to A.N.A.T., T.O., J.H.; U54CA163313 to K.A., M.S.; U54CA163308 to C.S.S., E.H.; U54CA163308-04S1 to C.S.S., J.A.T.; U54CA163261 to C.R.; U54CA163261-04S1 to J.C., A.K.; U54CA163262 to A.G.Z., D.C., C.D., T.L.; U54CA163262-04S1 to D.C., M.S.; and U54CA164336 to C.W.). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or the United States government.

Objective: To examine the rates of colorectal cancer (CRC) following a negative screening sigmoidoscopy., Design: Cohort study., Setting: An integrated healthcare delivery organisation in California, USA., Participants: 72,483 men and women aged 50 years and above who had a negative screening sigmoidoscopy between 1994 and 1996. Those at elevated risk of CRC due to inflammatory bowel disease, prior polyps or CRC, or a strong family history of CRC were excluded., Main Outcome Measures: Incidence rates of distal and proximal CRC. Standardised Incidence Ratios were used to compare annual incidence rates of distal and proximal CRC in the cohort to expected rates based on Surveillance, Epidemiology, and End Results data. Additionally, rate ratios (RR) and rate differences (RD) comparing the incidence rate of distal CRC in years 6+ postscreening with that in years 1-5 were calculated., Results: Incidence rates of distal CRC were lower than those in the San Francisco Bay area population at large during each of the first 10 years postsigmoidoscopy screening. However, the incidence of distal CRC rose steadily, from 3 per 100,000 in the first year of follow-up to 40 per 100,000 in the 10th year. During the second half of follow-up, the rate of distal CRC was twice as high as in the first half (RR 2 .08, 95% CI 1.38 to 3.16; RD 14 per 100,000 person-years, 95% CI 6 to 22)., Conclusions: Though still below population levels, the incidence of CRC during years 6-10 following a negative sigmoiodoscopy is appreciably higher than during the first 5 years., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aims: Screening colonoscopy's effectiveness in reducing risk of death from right colon cancers remains unclear. Methodological challenges of existing observational studies addressing this issue motivated the design of 'Effectiveness of Screening for Colorectal Cancer in Average-Risk Adults (SCOLAR)'., Methods: SCOLAR is a nested case-control study based on two large integrated health systems. This affords access to a large, well-defined historical cohort linked to integrated data on cancer outcomes, patient eligibility, test indications and important confounders., Results: We found electronic data adequate for excluding ineligible patients (except family history), but not the detailed information needed for test indication assignment., Conclusion: The lessons of SCOLAR's design and implementation may be useful for future studies seeking to evaluate the effectiveness of screening tests in community settings.

Background: It is unclear whether the higher rate of colorectal cancer (CRC) among non-Hispanic blacks (blacks) is due to lower rates of CRC screening or greater biologic risk., Objective: We aimed to evaluate whether blacks are more likely than non-Hispanic whites (whites) to develop distal colon neoplasia (adenoma and/or cancer) after negative flexible sigmoidoscopy (FSG)., Design: We analyzed data of participants with negative FSGs at baseline in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial who underwent repeat FSGs 3 or 5 years later. Subjects with polyps or masses were referred to their physicians for diagnostic colonoscopy. We collected and reviewed the records of diagnostic evaluations., Participants: Our analytic cohort consisted of 21,550 whites and 975 blacks., Main Measures: We did a comparison by race (whites vs. blacks) in the findings of polyps or masses at repeat FSG, the follow-up of abnormal test results and the detection of colorectal neoplasia at diagnostic colonoscopy., Key Results: At the follow-up FSG examination, 304 blacks (31.2 %) and 4183 whites (19.4 %) had abnormal FSG, [adjusted relative risk (RR) = 1.00; 95 % confidence interval (CI), 0.90-1.10]. However, blacks were less likely to undergo diagnostic colonoscopy (76.6 % vs. 83.1 %; RR = 0.90; 95 % CI, 0.84-0.96). Among all included patients, blacks had similar risk of any distal adenoma (RR = 0.86; 95 % CI, 0.65-1.14) and distal advanced adenoma (RR = 1.01; 95 % CI, 0.60-1.68). Similar results were obtained when we restricted our analysis to compliant subjects who underwent diagnostic colonoscopy (RR = 1.01; 95 % CI, 0.80-1.29) for any distal adenoma and (RR = 1.18; 95 % CI, 0.73-1.92) for distal advanced adenoma., Conclusions: We did not find any differences between blacks and whites in the risk of distal colorectal adenoma 3-5 years after negative FSG. However, follow-up evaluations were lower among blacks.

Introduction: Electronic health data are potentially valuable resources for evaluating colonoscopy screening utilization and effectiveness. The ability to distinguish screening colonoscopies from exams performed for other purposes is critical for research that examines factors related to screening uptake and adherence, and the impact of screening on patient outcomes, but distinguishing between these indications in secondary health data proves challenging. The objective of this study is to develop a new and more accurate algorithm for identification of screening colonoscopies using electronic health data., Methods: Data from a case-control study of colorectal cancer with adjudicated colonoscopy indication was used to develop logistic regression-based algorithms. The proposed algorithms predict the probability that a colonoscopy was indicated for screening, with variables selected for inclusion in the models using the Least Absolute Shrinkage and Selection Operator (LASSO)., Results: The algorithms had excellent classification accuracy in internal validation. The primary, restricted model had AUC= 0.94, sensitivity=0.91, and specificity=0.82. The secondary, extended model had AUC=0.96, sensitivity=0.88, and specificity=0.90., Discussion: The LASSO approach enabled estimation of parsimonious algorithms that identified screening colonoscopies with high accuracy in our study population. External validation is needed to replicate these results and to explore the performance of these algorithms in other settings.