Evaluation of Harms Reporting in U.S. Cancer Screening Guidelines.

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.

Up-to-Date Breast, Cervical, and Colorectal Cancer Screening Test Use in the United States, 2021.

INTRODUCTION: We examined national estimates of breast, cervical, and colorectal cancer (CRC) screening test use and compared them with Healthy People 2030 national targets. Test use in 2021 was compared with prepandemic estimates. METHODS: In 2022, we used 2021 National Health Interview Survey (NHIS) data to estimate proportions of adults up to date with US Preventive Services Task Force recommendations for breast (women aged 50-74 y), cervical (women aged 21-65 y), and CRC screening (adults aged 50-75 y) across sociodemographic and health care access variables. We compared age-standardized estimates from the 2021 and 2019 NHIS. RESULTS: Percentages of adults up to date in 2021 were 75.7% (95% CI, 74.4%-76.9%), 75.2% (95% CI, 73.9%-76.4%), and 72.2% (95% CI, 71.2%-73.2%) for breast, cervical, and CRC screening, respectively. Estimates were below 50% among those without a wellness check in 3 years (all screening types), among those without a usual source of care or insurance (aged <65 y) (breast and CRC screening), and among those residing in the US for less than 10 years (CRC screening). Percentages of adults who were up to date with breast and cervical cancer screening and colonoscopy were similar in 2019 and 2021. Fecal occult blood/fecal immunochemical test (FOBT/FIT) use was modestly higher in 2021 (P < .001). CONCLUSIONS: In 2021, approximately 1 in 4 adults of screening age were not up to date with breast, cervical, and CRC screening recommendations, and Healthy People 2030 national targets were not met. Disparities existed across several characteristics, particularly those related to health care access. Breast, cervical, and colonoscopy test use within recommended screening intervals approximated prepandemic levels. FOBT/FIT estimates were modestly higher in 2021.

Cancer screening in the U.S. through the COVID-19 pandemic, recovery, and beyond.

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.

Percentage Up to Date With Chest Computed Tomography Among Those Eligible for Lung Cancer Screening.

INTRODUCTION: Authors aimed to calculate the percentage up-to-date with testing in the context of lung cancer screening across 5 healthcare systems and evaluate differences according to patient and health system characteristics. METHODS: Lung cancer screening‒eligible individuals receiving care within the five systems in the Population-based Research to Optimize the Screening Process Lung consortium from October 1, 2018 to September 30, 2019 were included in analyses. Data collection was completed on June 15, 2021; final analyses were completed on April 1, 2022. Chest computed tomography scans and patient characteristics were obtained through electronic health records and used to calculate the percentage completing a chest computed tomography scan in the previous 12 months (considered up-to-date). The association of patient and healthcare system factors with being up-to-date was evaluated with adjusted prevalence ratios and 95% CIs using log-binomial regression models. RESULTS: There were 29,417 individuals eligible for lung cancer screening as of September 30, 2019; 8,333 (28.3%) were up-to-date with testing. Those aged 65-74 years (prevalence ratio=1.19; CI=1.15, 1.24, versus ages 55-64), those with chronic obstructive pulmonary disease (prevalence ratio=2.05; CI=1.98, 2.13), and those in higher SES census tracts (prevalence ratio=1.22; CI=1.16, 1.30, highest quintile versus lowest) were more likely to be up-to-date. Currently smoking (prevalence ratio=0.91; CI=0.88, 0.95), having a BMI ≥30 kg/m2 (prevalence ratio=0.83; CI=0.77, 0.88), identifying as Native Hawaiian or other Pacific Islander (prevalence ratio=0.79; CI=0.68, 0.92), and having a decentralized lung cancer screening program (prevalence ratio=0.77; CI=0.74, 0.80) were inversely associated with being up-to-date. CONCLUSIONS: The percentage up-to-date with testing among those eligible for lung cancer screening is well below up-to-date estimates for other types of cancer screening, and disparities in lung cancer screening participation remain.

Test performance metrics for breast, cervical, colon, and lung cancer screening: a systematic review.

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.

Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force.

BACKGROUND: Screening can detect prostate cancer at earlier, asymptomatic stages, when treatments might be more effective. PURPOSE: To update the 2002 and 2008 U.S. Preventive Services Task Force evidence reviews on screening and treatments for prostate cancer. DATA SOURCES: MEDLINE (2002 to July 2011) and the Cochrane Library Database (through second quarter of 2011). STUDY SELECTION: Randomized trials of prostate-specific antigen-based screening, randomized trials and cohort studies of prostatectomy or radiation therapy versus watchful waiting, and large observational studies of perioperative harms. DATA EXTRACTION: Investigators abstracted and checked study details and quality using predefined criteria. DATA SYNTHESIS: Of 5 screening trials, the 2 largest and highest-quality studies reported conflicting results. One found that screening was associated with reduced prostate cancer-specific mortality compared with no screening in a subgroup of men aged 55 to 69 years after 9 years (relative risk, 0.80 [95% CI, 0.65 to 0.98]; absolute risk reduction, 0.07 percentage point). The other found no statistically significant effect after 10 years (relative risk, 1.1 [CI, 0.80 to 1.5]). After 3 or 4 screening rounds, 12% to 13% of screened men had false-positive results. Serious infections or urine retention occurred after 0.5% to 1.0% of prostate biopsies. There were 3 randomized trials and 23 cohort studies of treatments. One good-quality trial found that prostatectomy for localized prostate cancer decreased risk for prostate cancer-specific mortality compared with watchful waiting through 13 years of follow-up (relative risk, 0.62 [CI, 0.44 to 0.87]; absolute risk reduction, 6.1%). Benefits seemed to be limited to men younger than 65 years. Treating approximately 3 men with prostatectomy or 7 men with radiation therapy instead of watchful waiting would each result in 1 additional case of erectile dysfunction. Treating approximately 5 men with prostatectomy would result in 1 additional case of urinary incontinence. Prostatectomy was associated with perioperative death (about 0.5%) and cardiovascular events (0.6% to 3%), and radiation therapy was associated with bowel dysfunction. LIMITATIONS: Only English-language articles were included. Few studies evaluated newer therapies. CONCLUSION: Prostate-specific antigen-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Cancer Screening Test Use-U.S., 2019.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Estimating Cancer Screening Sensitivity and Specificity Using Healthcare Utilization Data: Defining the Accuracy Assessment Interval.

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.

Racial Disparities in Adherence to Annual Lung Cancer Screening and Recommended Follow-Up Care: A Multicenter Cohort Study.

Rationale: Black patients receive recommended lung cancer screening (LCS) follow-up care less frequently than White patients, but it is unknown if this racial disparity persists across both decentralized and centralized LCS programs. Objectives: To determine adherence to American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS) recommendations among individuals undergoing LCS at either decentralized or centralized programs and to evaluate the association of race with LCS adherence. Methods: We performed a multicenter retrospective cohort study of patients receiving LCS at five heterogeneous U.S. healthcare systems. We calculated adherence to annual LCS among patients with a negative baseline screen (Lung-RADS 1 or 2) and recommended follow-up care among those with a positive baseline screen (Lung-RADS 3, 4A, 4B, or 4X) stratified by type of LCS program and evaluated the association between race and adherence using multivariable modified Poisson regression. Results: Of the 6,134 total individuals receiving LCS, 5,142 (83.8%) had negative baseline screens, and 992 (16.2%) had positive baseline screens. Adherence to both annual LCS (34.8% vs. 76.1%; P < 0.001) and recommended follow-up care (63.9% vs. 74.6%; P < 0.001) was lower at decentralized compared with centralized programs. Among individuals with negative baseline screens, a racial disparity in adherence was observed only at decentralized screening programs (interaction term, P < 0.001). At decentralized programs, Black race was associated with 27% reduced adherence to annual LCS (adjusted relative risk [aRR], 0.73; 95% confidence interval [CI], 0.63-0.84), whereas at centralized programs, no effect by race was observed (aRR, 0.98; 95% CI, 0.91-1.05). In contrast, among those with positive baseline screens, there was no significant difference by race for adherence to recommended follow-up care by type of LCS program (decentralized aRR, 0.95; 95% CI, 0.81-1.11; centralized aRR, 0.81; 95% CI, 0.71-0.93; interaction term, P = 0.176). Conclusions: In this large multicenter study of individuals screened for lung cancer, adherence to both annual LCS and recommended follow-up care was greater at centralized screening programs. Black patients were less likely to receive annual LCS than White patients at decentralized compared with centralized LCS programs. Our results highlight the need for further study of healthcare system-level mechanisms to optimize longitudinal LCS care.

Screening for prostate cancer with PSA testing: current status and future directions.

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.

Cumulative incidence of false-positive test results in lung cancer screening: a randomized trial.

BACKGROUND: 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. OBJECTIVE: 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. DESIGN: Randomized, controlled trial of low-dose CT versus chest radiography. (ClinicalTrials.gov registration number: NCT00006382) SETTING: Feasibility study for the ongoing National Lung Screening Trial. PATIENTS: 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). INTERVENTION: 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. MEASUREMENTS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSION: 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. PRIMARY FUNDING SOURCE: National Cancer Institute.

Do competing causes of mortality contribute to overdiagnosis in lung cancer screening?

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.

Clinical trial design and evidence-based outcomes in the study of liver diseases.

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.

Collaborative Modeling: Experience of the U.S. Preventive Services Task Force.

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.

Principles of cancer screening: lessons from history and study design issues.

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.