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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 U.S. Preventive Services Task Force recommends breast, cervical, and colorectal cancer screening to reduce mortality from these cancers, but screening use has been below national targets. The purpose of this study is to examine the proportion of screening-eligible adults who are up to date with these screenings and how screening use compares with Healthy People 2020 targets.Data from the 2019 National Health Interview Survey were used to examine the percentages of adults up to date with breast cancer screening among women aged 50‒74 years without previous breast cancer, cervical cancer screening among women aged 21‒65 years without previous cervical cancer or hysterectomy, and colorectal cancer screening among adults aged 50‒75 years without previous colorectal cancer. Estimates are presented by sociodemographic characteristics and healthcare access factors. Analyses were conducted in 2021.Percentages of adults up to date were 76.2% (95% CI= 75.0, 77.5) for breast cancer screening, 76.4% (95% CI= 75.2, 77.6) for cervical cancer screening, and 68.3% (95% CI= 67.3, 69.3) for colorectal cancer screening. Although some population subgroups met breast and colorectal cancer screening targets (81.1% and 70.5%, respectively), many did not, and cervical cancer screening was below the target for all examined subgroups. Lower education and income, nonmetropolitan county of residence (which included rural counties), no usual source of care or health insurance coverage, and Medicaid coverage were associated with lower screening test use.Estimated use of breast, cervical, and colorectal cancer screening tests based on the 2019 National Health Interview Survey were below national targets. Continued monitoring may allow for examination of screening trends, inform interventions, and track progress in eliminating disparities.

BACKGROUND: Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.METHODS: We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.FINDINGS: Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture INTERPRETATION: Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.FUNDING: Patient-Centered Outcomes Research Institute.

The effectiveness and efficiency of cancer screening in real-world settings depend on many factors, including test sensitivity and specificity. Outside of select experimental studies, not everyone receives a gold standard test that can serve as a comparator in estimating screening test accuracy. Thus, many studies of screening test accuracy use the passage of time to infer whether or not cancer was present at the time of the screening test, particularly for patients with a negative screening test. We define the accuracy assessment interval as the period of time after a screening test that is used to estimate the test's accuracy. We describe how the length of this interval may bias sensitivity and specificity estimates. We call for future research to quantify bias and uncertainty in accuracy estimates and to provide guidance on setting accuracy assessment interval lengths for different cancers and screening modalities.

Overdiagnosed cancers are those that are screen-detected but never would have been symptomatic during patients' lifetimes. Indolent cancers are overdiagnosed cancers. Non-indolent cancers can be overdiagnosed when patients die of causes other than the screen-detected cancer and would have, in the absence of screening, been asymptomatic and undiagnosed at the time of death. This is termed competing cause of mortality (CCM) overdiagnosis. Deaths soon after screen detection may represent CCM overdiagnosis. We examined time from screen-detection to death among the 35 participants in the National Lung Screening Trial (NLST) low-dose computed tomography arm with screen-detected lung cancer and died of non-lung-cancer causes. Seven participants died within 6 months, and 20 died more than 24 months after diagnosis. Deaths due to non-lung cancer causes soon after screen detection were uncommon, arguing against widespread CCM overdiagnosis in the NLST. However, CCM overdiagnosis is likely more frequent in community-based screening given the higher prevalence of comorbidities.

COVID-19 has proved enormously disruptive to the provision of cancer screening, which does not just represent an initial test but an entire process, including risk detection, diagnostic follow-up, and treatment. Successful delivery of services at all points in the process has been negatively affected by the pandemic. There is a void in empirical high-quality evidence to support a specific strategy for administering cancer screening during a pandemic and its resolution phase, but several pragmatic considerations can help guide prioritization efforts. Targeting guideline-eligible people who have never been screened, or those who are significantly out of date with screening, has the potential to maximize benefits now and into the future. Disruptions to care due to the pandemic could represent an unparalleled opportunity to reassess early detection programs towards an explicit, thoughtful, and just prioritization of populations historically experiencing cancer disparities. By focusing screening services on populations that have the most to gain, and by careful and deliberate planning for the period following the pandemic, we can positively affect cancer outcomes for all.

Screening has long been portrayed as an inherently beneficial activity that saves lives, rather than as a complex mixture of potential benefits and harms that must be carefully weighed for each modality. The early success of the Pap smear in reducing deaths from cervical cancer may have inadvertently fostered simplistic messaging about unqualified benefits of screening. Over time, large-scale randomized controlled trials (RCTs) of prostate and other cancers have highlighted the potential harms caused by mass screening programs (especially those related to overdiagnosis and unnecessary treatment) and have revealed the counterintuitive elements involved in evaluating such programs. The criteria for evaluation now extend beyond the performance criteria of the test itself to include the net balance of benefits, risks, and costs. PSA screening, widely used in the United States since the late 1980s, has now been removed from the list of routinely recommended procedures, based on evidence from RCTs.

Models can be valuable tools to address uncertainty, trade-offs, and preferences when trying to understand the effects of interventions. Availability of results from two or more independently developed models that examine the same question (comparative modeling) allows systematic exploration of differences between models and the effect of these differences on model findings. Guideline groups sometimes commission comparative modeling to support their recommendation process. In this commissioned collaborative modeling, modelers work with the people who are developing a recommendation or policy not only to define the questions to be addressed but ideally, work side-by-side with each other and with systematic reviewers to standardize selected inputs and incorporate selected common assumptions. This paper describes the use of commissioned collaborative modeling by the U.S. Preventive Services Task Force (USPSTF), highlighting the general challenges and opportunities encountered and specific challenges for some topics. It delineates other approaches to use modeling to support evidence-based recommendations and the many strengths of collaborative modeling compared with other approaches. Unlike systematic reviews prepared for the USPSTF, the commissioned collaborative modeling reports used by the USPSTF in making recommendations about screening have not been required to follow a common format, sometimes making it challenging to understand key model features. This paper presents a checklist developed to critically appraise commissioned collaborative modeling reports about cancer screening topics prepared for the USPSTF.

Early detection of cancer has held great promise and intuitive appeal in the medical community for well over a century. Its history developed in tandem with that of the periodic health examination, in which any deviations--subtle or glaring--from a clearly demarcated "normal" were to be rooted out, given the underlying hypothesis that diseases develop along progressive linear paths of increasing abnormalities. This model of disease development drove the logical deduction that early detection, by "breaking the chain" of cancer development, must be of benefit to affected individuals. In the latter half of the 20th century, researchers and guidelines organizations began to explicitly challenge the core assumptions underpinning many clinical practices. A move away from intuitive thinking began with the development of evidence-based medicine. One key method developed to explicitly quantify the overall risk-benefit profile of a given procedure was the analytic framework. The shift away from pure deductive reasoning and reliance on personal observation was driven, in part, by a rising awareness of critical biases in cancer screening that can mislead clinicians, including healthy volunteer bias, length-biased sampling, lead-time bias, and overdiagnosis. A new focus on the net balance of both benefits and harms when determining the overall worth of an intervention also arose: it was recognized that the potential downsides of early detection were frequently overlooked or discounted because screening is performed on basically healthy persons and initially involves relatively noninvasive methods. Although still inconsistently applied to early detection programs, policies, and belief systems in the United States, an evidence-based approach is essential to counteract the misleading--even potentially harmful--allure of intuition and individual observation.

PURPOSE Multiple cancer screening tests have been advocated for the general population; however, clinicians and patients are not always well-informed of screening burdens. We sought to determine the cumulative risk of a false-positive screening result and the resulting risk of a diagnostic procedure for an individual participating in a multimodal cancer screening program. METHODS Data were analyzed from the intervention arm of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial to determine the effects of prostate, lung, colorectal, and ovarian cancer screening on disease-specific mortality. The 68,436 participants, aged 55 to 74 years, were randomized to screening or usual care. Women received serial serum tests to detect cancer antigen 125 (CA-125), transvaginal sonograms, posteroanterior-view chest radiographs, and flexible sigmoidoscopies. Men received serial chest radiographs, flexible sigmoidoscopies, digital rectal examinations, and serum prostate-specific antigen tests. Fourteen screening examinations for each sex were possible during the 3-year screening period. RESULTS After 14 tests, the cumulative risk of having at least 1 false-positive screening test is 60.4% (95% CI, 59.8%–61.0%) for men, and 48.8% (95% CI, 48.1%–49.4%) for women. The cumulative risk after 14 tests of undergoing an invasive diagnostic procedure prompted by a false-positive test is 28.5% (CI, 27.8%–29.3%) for men and 22.1% (95% CI, 21.4%–22.7%) for women. CONCLUSIONS For an individual in a multimodal cancer screening trial, the risk of a false-positive finding is about 50% or greater by the 14th test. Physicians should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer screening.

Current medical training often does not include the formal study of trial design, forcing clinicians to acquire this knowledge independently. This article reviews the foundational elements of clinical trial design. An overarching hierarchy of clinical evidence is introduced, and the relative strengths and limitations of the major types of study designs are discussed. A corollary to the hierarchy of evidence in trial designs is proposed for trial outcomes: the ‘‘pyramid of endpoints.” This pyramid represents a spectrum of outcomes from tangible health events to intermediate markers with no direct physical impact on an individual. The potential advantages and difficulties inherent in the use of surrogate endpoints for final health outcomes are explored. Randomized controlled trials utilizing ‘‘hard” clinical endpoints are advocated as the most efficient and reliable way to directly assess the benefits and harms of a therapy; however, using a case study of treatments for hepatocellular carcinoma, we highlight the challenges that can complicate even the highest levels of evidence. All trials have a ‘‘signal-to-noise” ratio – this review emphasizes the need for careful and deliberate consideration of the potential limitations of every study, and provides basic tools to assist the practitioner in identifying common pitfalls of clinical trials. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.

The concept of early detection of cancer holds great promise and intuitive appeal. However, powerful biases can mislead clinicians when evaluating the efficacy of screening tests by clinical observation alone. Selection bias, lead-time bias, length-biased sampling, and overdiagnosis are counterintuitive concepts with critical implications for early-detection efforts. This article explains these biases and other common confounders in cancer screening. The most direct and reliable way to avoid being led astray by intuitions is through the use of randomized controlled trials.

The ultimate utility of the serum prostate specific antigen (PSA) assay as a screening test for reducing prostate cancer mortality has been an area of intense controversy since its introduction. PSA testing was not initially envisioned as a screening tool, but as a way to evaluate treatment responses in men with prostate cancer. Far in advance of evidence from randomized trials, the rapid and widespread uptake of PSA screening into US practice was initially driven by the intuitively logical assumption that the earlier one detects a malignancy, the more likely treatment is to be curative while minimizing associated harms. However, a growing body of observational evidence began to point to a substantial burden of associated overdiagnosis and overtreatment triggered by PSA testing. The interim results of several randomized clinical trials specifically designed to evaluate the impact of PSA testing on prostate cancer mortality have recently become available, but their incongruent results seem to have added fuel to the debate. This article presents a review of the literature on screening for prostate cancer with PSA testing; we include a detailed discussion of potential explanations for the contradictory results of the two largest randomized trials as well as reflections on the future of prostate cancer screening.

PURPOSE: The study aimed to describe modifications in diet and eating patterns made by community-living people to manage fecal incontinence (FI), and to compare these differences according to sex, age, and FI severity. SUBJECTS AND SETTINGS: Subjects were 188 community-living adults (77% female, 92% white, 34% aged 65 years or older) in the upper Midwest who participated in a study about managing FI with dietary fiber. METHODS: Subjects were interviewed about diet and eating pattern changes that they made to manage FI, and self-reported demographic data. FI severity was recorded daily. RESULTS: Fifty-five percent of participants perceived that some foods worsen their FI (eg, fatty or spicy foods and dairy products). More women than men (40% vs 18%, P = .008) reported avoiding foods to manage FI. A greater percentage of younger than older people believed that fatty/greasy foods (15% vs 4%) and alcohol (14% vs 3%) worsened their FI. Subjects with a higher FI severity score appeared to wait until FI was more severe before restricting caffeine than those with lower severity scores (22.2 ± 9.8 vs 11.69 ± 8.3, P = .034). One-third of subjects consumed foods rich in dietary fiber to prevent FI. Subjects also reported altered eating or cooking patterns, skipping meals, or eating at consistent times to manage FI. CONCLUSIONS: Diet modification for managing FI incorporates restriction of some foods, along with adding others foods to the diet. Nursing assessments of self-care practices for FI should include diet and eating pattern changes when developing a plan of care.

Direct-to-consumer promotion of lung cancer screening has increased, especially low-dose computed tomography (CT). However, screening exposes healthy persons to potential harms, and cumulative false-positive rates for low-dose CT have never been formally reported.To quantify the cumulative risk that a person who participated in a 1- or 2-year lung cancer screening examination would receive at least 1 false-positive result, as well as rates of unnecessary diagnostic procedures.Randomized, controlled trial of low-dose CT versus chest radiography. (ClinicalTrials.gov registration number: NCT00006382)Feasibility study for the ongoing National Lung Screening Trial.Current or former smokers, aged 55 to 74 years, with a smoking history of 30 pack-years or more and no history of lung cancer (n = 3190).Random assignment to low-dose CT or chest radiography with baseline and 1 repeated annual screening; 1-year follow-up after the final screening. Randomization was centralized and stratified by age, sex, and study center.False-positive screenings, defined as a positive screening with a completed negative work-up or 12 months or more of follow-up with no lung cancer diagnosis.By using a Kaplan-Meier analysis, a person's cumulative probability of 1 or more false-positive low-dose CT examinations was 21% (95% CI, 19% to 23%) after 1 screening and 33% (CI, 31% to 35%) after 2. The rates for chest radiography were 9% (CI, 8% to 11%) and 15% (CI, 13% to 16%), respectively. A total of 7% of participants with a false-positive low-dose CT examination and 4% with a false-positive chest radiography had a resulting invasive procedure.Screening was limited to 2 rounds. Follow-up after the second screening was limited to 12 months. The false-negative rate is probably an underestimate.Risks for false-positive results on lung cancer screening tests are substantial after only 2 annual examinations, particularly for low-dose CT. Further study of resulting economic, psychosocial, and physical burdens of these methods is warranted.National Cancer Institute.

OBJECTIVE To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at near-normal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy. METHODS Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome. RESULTS After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conventional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; P < .001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (P < .001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. CONCLUSION The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning. TRIAL REGISTRATION (clinicaltrials.gov) Identifiers: NCT00360815 and NCT00360893.

CRA1502 Background: Screening with low-dose computed tomography (LDCT) has been promoted as the best hope for curing lung cancer. However, cumulative false-positive (FP) rates have never been formally reported. We quantified the cumulative risk of receiving ≥1 FP test for individuals in a lung cancer screening program with 2 annual screens. Methods: Prior to the ongoing National Lung Screening Trial (NLST), a definitive randomized controlled trial of LDCT versus single-view chest xray (CXR), a randomized controlled feasibility trial was conducted at six NLST centers. Participants (55–74 years at entry, current or former smokers, and ≥ 30 pack/year smoking history) were offered a baseline LDCT (N = 1,610) or CXR (N = 1,580), and one repeat annual screen, and were followed for 1 year after their final screen. Participants who received at least one screening exam were eligible for this analysis. Exclusion criteria included chest CT in the past 24 months or history of lung cancer. A positive screen was any noncalcified nodule ≥ 4mm or other radiographic finding deemed suspicious for cancer. A FP was a positive screen with: 1) a completed negative work-up, or 2) ≥ 12 months follow-up with no cancer diagnosis. Results: Using a Kaplan-Meier analysis, an individual's cumulative probability of ≥ 1 FP LDCT was 21% (95% CI, 19%–23%) after one screen and 33% (95% CI, 30%–35%) after two. The cumulative probability of ≥ 1 FP CXR was 9% (95% CI, 8%–11%) and 15% (95% CI, 13%–16%) after one and two screens, respectively. On multivariable analysis, higher odds of FP for LDCT were associated with increased participant age (>64 years) (OR 1.34, 95% CI, 1.04–1.73); current versus former smoker status trended toward higher FP odds (OR 1.22, 95% CI, 0.95–1.56). 6.6% of participants with a FP LDCT underwent an invasive diagnostic follow-up procedure; 1.6% had major surgery. 4.2% of participants with a FP CXR underwent an invasive diagnostic follow-up procedure; 1.9% had major surgery. Conclusions: Risks of LDCT FP are substantial after only two annual examinations; the potential resulting economic, psychosocial, and physical burdens of this modality warrant investigation. No significant financial relationships to disclose.

CRA1502 Background: Screening with low-dose computed tomography (LDCT) has been promoted as the best hope for curing lung cancer. However, cumulative false-positive (FP) rates have never been formally reported. We quantified the cumulative risk of receiving ≥1 FP test for individuals in a lung cancer screening program with 2 annual screens. Methods: Prior to the ongoing National Lung Screening Trial (NLST), a definitive randomized controlled trial of LDCT versus single-view chest xray (CXR), a randomized controlled feasibility trial was conducted at six NLST centers. Participants (55–74 years at entry, current or former smokers, and ≥ 30 pack/year smoking history) were offered a baseline LDCT (N = 1,610) or CXR (N = 1,580), and one repeat annual screen, and were followed for 1 year after their final screen. Participants who received at least one screening exam were eligible for this analysis. Exclusion criteria included chest CT in the past 24 months or history of lung cancer. A positive screen was any no...