Estimation of Cancer Deaths Averted From Prevention, Screening, and Treatment Efforts, 1975-2020.

Importance: Cancer mortality has decreased over time, but the contributions of different interventions across the cancer control continuum to averting cancer deaths have not been systematically evaluated across major cancer sites.

Objective: To quantify the contributions of prevention, screening (to remove precursors [interception] or early detection), and treatment to cumulative number of cancer deaths averted from 1975 to 2020 for breast, cervical, colorectal, lung, and prostate cancers.

Design, Setting, And Participants: In this model-based study using population-level cancer mortality data, outputs from published models developed by the Cancer Intervention and Surveillance Modeling Network were extended to quantify cancer deaths averted through 2020.

The Association of Where Patients with Prostate Cancer Live and Receive Care on Racial Treatment Inequities.

Black individuals are less likely to be treated for prostate cancer even though they are more than twice as likely to die compared to White individuals. The complex causes of these inequities are influenced by social and structural factors, including racism, which contribute to the differential delivery of care. This study investigates how factors related to the location of where individuals live and receive care affect treatment inequities for prostate cancer between Black and White individuals.

Projected Outcomes of Reduced-Biopsy Management of Grade Group 1 Prostate Cancer: Implications for Relabeling.

Background: Implications of relabeling grade group (GG) 1 prostate cancer as non-cancer will depend on the recommended active surveillance (AS) strategy. Whether relabeling should prompt de-intensifying, PSA-based active monitoring approaches is unclear. We investigated outcomes of biopsy-based AS strategies vs PSA-based active monitoring for GG1 diagnoses under different patient adherence rates.

Trends in age and prostate-specific antigen at prostate cancer diagnosis between 2010 and 2019.

Recent studies have shown that de novo metastatic prostate cancer incidence in the United States increased from 2010 to 2019. Plausible explanations include delayed detection after recommendations against prostate cancer screening or upstaging associated with use of more sensitive imaging technologies. Using Surveillance, Epidemiology, and End Results patient cases and controlling for aging of the population, we found the median age and prostate-specific antigen (PSA) level at prostate cancer diagnosis increased by 1.

Prostate-Specific Antigen Screening and Prostate Cancer Mortality: An Emulation of Target Trials in US Medicare.

Purpose: No consensus about the effectiveness of prostate-specific antigen (PSA) screening exists among clinical guidelines, especially for the elderly. Randomized trials of PSA screening have yielded different results, partly because of variations in adherence, and it is unlikely that new trials will be conducted. Our objective was to estimate the effect of annual PSA screening on prostate cancer (PC) mortality in Medicare beneficiaries age 67-84 years.

Asymptomatic Incidence of Monoclonal Gammopathy of Undetermined Significance and Preclinical Duration to Myeloma Diagnosis: A Modeling Study.

Background: Monoclonal gammopathy of undetermined significance (MGUS) is the premalignant condition of multiple myeloma. Given a lack of population-based screening for MGUS and its asymptomatic nature, the epidemiology of MGUS remains unknown. This study estimated age- and race/ethnicity-specific MGUS incidence and preclinical duration from MGUS to multiple myeloma in the United States.

Breast density and risk of breast cancer: masking and detection bias.

Breast density is associated with risk of breast cancer (BC) diagnosis, impacting risk prediction tools and patient notification policies. Density affects mammography sensitivity and may influence screening intensity. Therefore, the observed association between density and BC diagnosis may not reflect the relationship between density and disease risk.

Lifetime Health and Economic Outcomes of Biparametric Magnetic Resonance Imaging as First-Line Screening for Prostate Cancer : A Decision Model Analysis.

Background: Contemporary prostate cancer (PCa) screening uses first-line prostate-specific antigen (PSA) testing, possibly followed by multiparametric magnetic resonance imaging (mpMRI) for men with elevated PSA levels. First-line biparametric MRI (bpMRI) screening has been proposed as an alternative.

Objective: To evaluate the comparative effectiveness and cost-effectiveness of first-line bpMRI versus PSA-based screening.

Considerations for using potential surrogate endpoints in cancer screening trials.

The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Review aims to highlight the issues underlying the choice and use of surrogate endpoints for cancer screening trials, to propose criteria for when and how we might use such endpoints, and to suggest possible candidates.

Projecting the Impact of Multi-Cancer Early Detection on Late-Stage Incidence Using Multi-State Disease Modeling.

Background: Downstaging-reduction in late-stage incidence-has been proposed as an endpoint in randomized trials of multi-cancer early detection (MCED) tests. How downstaging depends on test performance and follow-up has been studied for some cancers but is understudied for cancers without existing screening and for MCED tests that include these cancer types.

Methods: We develop a model for cancer natural history that can be fit to registry incidence patterns under minimal inputs and can be estimated for solid cancers without existing screening.

Prediagnostic evaluation of multicancer detection tests: design and analysis considerations.

There is growing interest in multicancer detection tests, which identify molecular signals in the blood that indicate a potential preclinical cancer. A key stage in evaluating these tests is a prediagnostic performance study, in which investigators store specimens from asymptomatic individuals and later test stored specimens from patients with cancer and a random sample of controls to determine predictive performance. Performance metrics include rates of cancer-specific true-positive and false-positive findings and a cancer-specific positive predictive value, with the latter compared with a decision-analytic threshold.

The Prostate Cancer Active Lifestyle Study (PALS): A randomized controlled trial of diet and exercise in overweight and obese men on active surveillance.

Background: Active surveillance (AS) is increasingly used to monitor patients with lower risk prostate cancer (PCa). The Prostate Cancer Active Lifestyle Study (PALS) was a randomized controlled trial to determine whether weight loss improves obesity biomarkers on the causal pathway to progression in patients with PCa on AS.

Methods: Overweight/obese men (body mass index >25 kg/m) diagnosed with PCa who elected AS were recruited.

Implementation outcomes of the integrated district evidence to action (IDEAs) program to reduce neonatal mortality in central Mozambique: an application of the RE-AIM evaluation framework.

Background: Scarce evidence exists on audit and feedback implementation processes in low-resource health systems. The Integrated District Evidence to Action (IDEAs) is a multi-component audit and feedback strategy designed to improve the implementation of maternal and child guidelines in Mozambique. We report IDEAs implementation outcomes.

Isolating the Drivers of Racial Inequities in Prostate Cancer Treatment.

Background: Black individuals in the United States are less likely than White individuals to receive curative therapies despite a 2-fold higher risk of prostate cancer death. While research has described treatment inequities, few studies have investigated underlying causes.

Methods: We analyzed a cohort of 40,137 Medicare beneficiaries (66 and older) linked to the Surveillance Epidemiology and End Results (SEER) cancer registry who had clinically significant, non-metastatic (cT1-4N0M0, grade group 2-5) prostate cancer (diagnosed 2010-2015).

Temporal effect of imatinib adherence on time to remission in chronic myeloid leukemia patients.

Introduction: Adherence to imatinib in chronic myeloid leukemia (CML) patients is estimated to be as low as 70% despite its clinical benefit, and our understanding of the impact of nonadherence in this population is limited. This study presents a novel application of the Alternating Conditional Estimation (ACE) algorithm in newly diagnosed CML patients to map the full dose-response curve (DRC) and determine how the strength of this curve varies over time.

Methods: We applied the ACE algorithm alongside a backward elimination procedure to detect the presence of time dependence and nonlinearity in the relationship between imatinib adherence and time-to-remission.

Racial disparities in prostate cancer mortality: a model-based decomposition of contributing factors.

To investigate the relative contributions of natural history and clinical interventions to racial disparities in prostate cancer mortality in the United States, we extended a model that was previously calibrated to Surveillance, Epidemiology, and End Results (SEER) incidence rates for the general population and for Black men. The extended model integrated SEER data on curative treatment frequencies and cancer-specific survival. Starting with the model for all men, we replaced up to 9 components with corresponding components for Black men, projecting age-standardized mortality rates for ages 40-84 years at each step.

Revisiting the standard blueprint for biomarker development to address emerging cancer early detection technologies.

Novel liquid biopsy technologies are creating a watershed moment in cancer early detection. Evidence supporting population screening is nascent, but a rush to market the new tests is prompting cancer early detection researchers to revisit the standard blueprint that the Early Detection Research Network established to evaluate novel screening biomarkers. In this commentary, we review the Early Detection Research Network's Phases of Biomarker Development (PBD) for rigorous evaluation of novel early detection biomarkers and discuss both hazards and opportunities involved in expedited evaluation.

Screening for lung cancer: 2023 guideline update from the American Cancer Society.

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer.

Multicancer Early Detection Tests: An Overview of Early Results From Prospective Clinical Studies and Opportunities for Oncologists.

A multitude of blood-based multicancer early detection (MCED) tests assessing cancer-related alterations in circulating genomic analytes and other associated signatures are currently being developed with the potential to disrupt current single-organ screening paradigms. Pathways for clinical implementation of these novel MCED tests have not been delineated, particularly for the patients with signal positive results requiring additional confirmatory testing. In this overview, we highlight early results from prospective clinical studies testing the efficacy of genomic MCED tests in cohorts of patients without known cancer diagnoses.

Benefits and harms of prostate specific antigen testing according to Australian guidelines.

Guidelines for prostate specific antigen (PSA) testing in Australia recommend that men at average risk of prostate cancer who have been informed of the benefits and harms, and who decide to undergo regular testing, should be offered testing every 2 years from 50 to 69 years. This study aimed to estimate the benefits and harms of regular testing in this context. We constructed Policy1-Prostate, a discrete event microsimulation platform of the natural history of prostate cancer and prostate cancer survival, and PSA testing patterns and subsequent management in Australia.

Prostate cancer screening in African American men: a review of the evidence.

Background: Prostate cancer is the most diagnosed cancer in African American men, yet prostate cancer screening regimens in this group are poorly guided by existing evidence, given underrepresentation of African American men in prostate cancer screening trials. It is critical to optimize prostate cancer screening and early detection in this high-risk group because underdiagnosis may lead to later-stage cancers at diagnosis and higher mortality while overdiagnosis may lead to unnecessary treatment.

Methods: We performed a review of the literature related to prostate cancer screening and early detection specific to African American men to summarize the existing evidence available to guide health-care practice.