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. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.

Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society.

The American Cancer Society (ACS) recommends that individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation). The ACS recommends that individuals aged >65 years who have no history of cervical intraepithelial neoplasia grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening (qualified recommendation). These new screening recommendations differ in 4 important respects compared with the 2012 recommendations: 1) The preferred screening strategy is primary HPV testing every 5 years, with cotesting and cytology alone acceptable where access to US Food and Drug Administration-approved primary HPV testing is not yet available; 2) the recommended age to start screening is 25 years rather than 21 years; 3) primary HPV testing, as well as cotesting or cytology alone when primary testing is not available, is recommended starting at age 25 years rather than age 30 years; and 4) the guideline is transitional, ie, options for screening with cotesting or cytology alone are provided but should be phased out once full access to primary HPV testing for cervical cancer screening is available without barriers. Evidence related to other relevant issues was reviewed, and no changes were made to recommendations for screening intervals, age or criteria for screening cessation, screening based on vaccination status, or screening after hysterectomy. Follow-up for individuals who screen positive for HPV and/or cytology should be in accordance with the 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors.

Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250-281. © 2018 American Cancer Society.

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. DESIGN: Decision analysis using a microsimulation model. DATA SOURCES: Surveillance, Epidemiology, and End Results database; randomized trials. TARGET POPULATION: U.S. men aged 55 years with no prior screening or PCa diagnosis. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care system. INTERVENTION: Biennial screening to age 69 years using first-line PSA testing (test-positive threshold, 4 µg/L) with or without second-line mpMRI or first-line bpMRI (test-positive threshold, PI-RADS [Prostate Imaging Reporting and Data System] 3 to 5 or 4 to 5), followed by biopsy guided by MRI or MRI plus transrectal ultrasonography. OUTCOME MEASURES: Screening tests, biopsies, diagnoses, overdiagnoses, treatments, PCa deaths, quality-adjusted and unadjusted life-years saved, and costs. RESULTS OF BASE-CASE ANALYSIS: For 1000 men, first-line bpMRI versus first-line PSA testing prevented 2 to 3 PCa deaths and added 10 to 30 life-years (4 to 11 days per person) but increased the number of biopsies by 1506 to 4174 and the number of overdiagnoses by 38 to 124 depending on the biopsy imaging scheme. At conventional cost-effectiveness thresholds, first-line PSA testing with mpMRI followed by either biopsy approach for PI-RADS 4 to 5 produced the greatest net monetary benefits. RESULTS OF SENSITIVITY ANALYSIS: First-line PSA testing remained more cost-effective even if bpMRI was free, all men with low-risk PCa underwent surveillance, or screening was quadrennial. LIMITATION: Performance of first-line bpMRI was based on second-line mpMRI data. CONCLUSION: Decision analysis suggests that comparative effectiveness and cost-effectiveness of PCa screening are driven by false-positive results and overdiagnoses, favoring first-line PSA testing with mpMRI over first-line bpMRI. PRIMARY FUNDING SOURCE: National Cancer Institute.

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. We present the current landscape and challenges, and discuss lessons and shortcomings from the therapeutic trial setting. It is hugely challenging to validate a surrogate endpoint, even with carefully designed clinical studies. Nevertheless, we consider whether there are candidates that might satisfy the requirements defined by research and regulatory bodies.

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. The model was calibrated to pre-PSA (before 1985) prostate cancer incidence and mortality and validated against incidence and mortality trends from 1985 to 2011 and international trials. The model predictions were concordant with trials and Australian observed incidence and mortality data from 1985 to 2011. Out of 1000 men who choose to test according to the guidelines, 36 [21-41] men will die from prostate cancer and 126 [119-133] men will be diagnosed with prostate cancer, compared with 50 [47-54] and 94 [90-98] men who do not test, respectively. During the 20 years of active PSA testing, 32.3% [25.6%-38.8%] of all PSA-test detected cancers are overdiagnosed cases that is, 30 [21-42] out of 94 [83-107] PSA-test detected cancers. Australian men choosing to test with PSA every two years from 50 to 69 will reduce their risk of ever dying from prostate cancer and incur a risk of overdiagnosis: for every man who avoids dying from prostate cancer, two will be overdiagnosed with prostate cancer between 50 and 69 years of age. Australian men, with health professionals, can use these results to inform decision-making about PSA testing.

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/m2) diagnosed with PCa who elected AS were recruited. The intervention was a 6-month, individually delivered, structured diet and exercise program adapted from the Diabetes Prevention Program with a 7% weight loss goal from baseline. Control participants attended one session reviewing the US Dietary and Physical Activity Guidelines. The primary outcome was change in glucose regulation from baseline to the end of the 6-month intervention, which was measured by fasting plasma glucose, C-peptide, insulin, insulin-like growth factor 1, insulin-like growth factor binding protein-3, adiponectin, and homeostatic model assessment for insulin resistance. RESULTS: Among 117 men who were randomized, 100 completed the trial. The mean percentage weight loss was 7.1% and 1.8% in the intervention and control arms, respectively (adjusted between-group mean difference, -6.0 kg; 95% confidence interval, -8.0, -4.0). Mean percentage changes from baseline for insulin, C-peptide, and homeostatic model assessment for insulin resistance in the intervention arm were -23%, -16%, and -25%, respectively, compared with +6.9%, +7.5%, and +6.4%, respectively, in the control arm (all p for intervention effects ≤ .003). No significant between-arm differences were detected for the other biomarkers. CONCLUSIONS: Overweight/obese men with PCa undergoing AS who participated in a lifestyle-based weight loss intervention successfully met weight loss goals with this reproducible lifestyle intervention and experienced improvements in glucose-regulation biomarkers associated with PCa progression.

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. METHODS: IDEAs was implemented in 154 health facilities across 12 districts in Manica and Sofala provinces between 2016 and 2020 and evaluated using a quasi-experimental design guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Reach is the proportion of pregnant women attending IDEAs facilities. Adoption is the proportion of facilities initiating audit and feedback meetings. Implementation is the fidelity to the strategy components, including readiness assessments, meetings (frequency, participation, action plan development), and targeted financial support and supervision. Maintenance is the sustainment at 12, 24, and 54 months. RESULTS: Across both provinces, 56% of facilities were exposed to IDEAs (target 57%). Sixty-nine and 73% of pregnant women attended those facilities' first and fourth antenatal consultations (target 70%). All facilities adopted the intervention. 99% of the expected meetings occurred with an average interval of 5.9 out of 6 months. Participation of maternal and child managers was high, with 3076 attending meetings, of which 64% were from the facility, 29% from the district, and 7% from the province level. 97% of expected action plans were created, and 41 specific problems were identified. "Weak diagnosis or management of obstetric complications" was identified as the main problem, and "actions to reinforce norms and protocols" was the dominant subcategory of micro-interventions selected. Fidelity to semiannual readiness assessments was low (52% of expected facilities), and in completing micro-interventions (17% were completed). Ninety-six and 95% of facilities sustained the intervention at 12 and 24 months, respectively, and 71% had completed nine cycles at 54 months. CONCLUSION: Maternal and child managers can lead audit and feedback processes in primary health care in Mozambique with high reach, adoption, and maintenance. The IDEAs strategy should be adapted to promote higher fidelity around implementing action plans and conducting readiness assessments. Adding effectiveness to these findings will help to inform strategy scale-up.

Cancer Stage Compared With Mortality as End Points in Randomized Clinical Trials of Cancer Screening: A Systematic Review and Meta-Analysis.

Importance: Randomized clinical trials of cancer screening typically use cancer-specific mortality as the primary end point. The incidence of stage III-IV cancer is a potential alternative end point that may accelerate completion of randomized clinical trials of cancer screening. Objective: To compare cancer-specific mortality with stage III-IV cancer as end points in randomized clinical trials of cancer screening. Design, Setting, and Participants: This meta-analysis included 41 randomized clinical trials of cancer screening conducted in Europe, North America, and Asia published through February 19, 2024. Data extracted included numbers of participants, cancer diagnoses, and cancer deaths in the intervention and comparison groups. For each clinical trial, the effect of screening was calculated as the percentage reduction between the intervention and comparison groups in the incidence of participants with cancer-specific mortality and stage III-IV cancer. Exposures: Randomization to a cancer screening test or to a comparison group in a clinical trial of cancer screening. Main Outcomes and Measures: End points of cancer-specific mortality and incidence of stage III-IV cancer were compared using Pearson correlation coefficients with 95% CIs, linear regression, and fixed-effects meta-analysis. Results: The included randomized clinical trials tested benefits of screening for breast (n = 6), colorectal (n = 11), lung (n = 12), ovarian (n = 4), prostate (n = 4), and other cancers (n = 4). Correlation between reductions in cancer-specific mortality and stage III-IV cancer varied by cancer type (I2 = 65%; P = .02). Correlation was highest for trials that screened for ovarian (Pearson ρ = 0.99 [95% CI, 0.51-1.00]) and lung (Pearson ρ = 0.92 [95% CI, 0.72-0.98]) cancers, moderate for breast cancer (Pearson ρ = 0.70 [95% CI, -0.26 to 0.96]), and weak for colorectal (Pearson ρ = 0.39 [95% CI, -0.27 to 0.80]) and prostate (Pearson ρ = -0.69 [95% CI, -0.99 to 0.81]) cancers. Slopes from linear regression were estimated as 1.15 for ovarian cancer, 0.75 for lung cancer, 0.40 for colorectal cancer, 0.28 for breast cancer, and -3.58 for prostate cancer, suggesting that a given magnitude of reduction in incidence of stage III-IV cancer produced different magnitudes of change in incidence of cancer-specific mortality (P for heterogeneity = .004). Conclusions and Relevance: In randomized clinical trials of cancer screening, incidence of late-stage cancer may be a suitable alternative end point to cancer-specific mortality for some cancer types, but is not suitable for others. These results have implications for clinical trials of multicancer screening tests.

Racial inequities in the quality of surgical care among Medicare beneficiaries with localized prostate cancer.

BACKGROUND: US Black men are twice as likely to die from prostate cancer as men of other races. Lower quality care may contribute to this higher death rate. METHODS: Sociodemographic and clinical data were obtained for men in Surveillance, Epidemiology, and End Results-Medicare diagnosed with clinically localized prostate cancer (cT1-4N0/xM0/x) and managed primarily by radical prostatectomy (2005-2015). Surgical volume was determined for facility and surgeon. Relationships between race, surgeon and/or facility volume, and characteristics of treating facility with survival (all-cause and cancer-specific) were assessed using multivariable Cox regression and competing risk analysis. RESULTS: Black men represented 6.7% (n = 2123) of 31,478 cohort. They were younger at diagnosis, had longer time from diagnosis to surgery, lower socioeconomic status, higher prostate-specific antigen (PSA), and higher comorbid status compared with men of other races (p < .001). They were less likely to receive care from a surgeon or facility in the top volume percentile (p < .001); less likely to receive surgical care at a National Cancer Institute-designated cancer center and more likely seen at a minority-serving hospital; and less likely to travel ≥50 miles for surgical care. On multivariable analysis stratified by surgical volume, Black men receiving care from a surgeon or facility with lower volumes demonstrated increased risk of prostate cancer mortality (hazard ratio, 1.61; 95% confidence interval, 1.01-2.69) adjusting for age, clinical stage, PSA, and comorbidity index. CONCLUSIONS: Black Medicare beneficiaries with prostate cancer more commonly receive care from surgeons and facilities with lower volumes, likely affecting surgical quality and outcomes. Access to high-quality prostate cancer care may reduce racial inequities in disease outcomes, even among insured men. PLAIN LANGUAGE SUMMARY: Black men are twice as likely to die of prostate cancer than other US men. Lower quality care may contribute to higher rates of prostate cancer death. We used surgical volume to evaluate the relationship between race and quality of care. Black Medicare beneficiaries with prostate cancer more commonly received care from surgeons and facilities with lower volumes, correlating with a higher risk of prostate cancer death and indicating scarce resources for care. Access to high-quality prostate cancer care eases disparities in disease outcomes. Patient-centered interventions that increase access to high-quality care for Black men with prostate cancer are needed.

Modeling the impact of novel systemic treatments on lung cancer screening benefits.

BACKGROUND: Since low-dose computed tomography (LDCT) screening was shown to be effective in the National Lung Screening Trial (NLST), novel targeted therapies and immunotherapies for advanced lung cancer have become available. This study investigated the impact of these treatment advances on the expected benefits of LDCT screening. METHODS: A microsimulation model of LDCT screening for high-risk individuals under standard systemic treatments (chemotherapy and radiation therapy) and novel treatments (immunotherapy and targeted therapy) was used. The model assumed a reduction in advanced-stage disease consistent with the NLST, and given the stage at diagnosis, it projected survival. The disease-specific relative mortality reduction (MR) due to LDCT screening was projected in the trial setting and in a population eligible for LDCT screening under the current US Preventive Services Task Force (USPSTF) recommendations. RESULTS: The availability of novel treatments reduced the MR in the LDCT arm of the NLST from 15% to 13.5% and the number of lung cancer deaths prevented from 310 to 224 per 100,000 persons screened. Over 10 years, population LDCT screening based on USPSTF recommendations prevented 374 lung cancer deaths per 100,000 under standard treatments (13.3% MR) and 236 per 100,000 under fully adopted novel treatments (10.6% MR). The number needed to screen to avert one death over 10 years was 270 under standard treatments and 440 under novel treatments. CONCLUSIONS: The transition from standard systemic treatments to novel treatments is expected to reduce the relative and absolute mortality benefits of LDCT screening. Benefit-harm tradeoffs of LDCT screening are likely to change as novel treatments become widespread.

Early Detection of Prostate Cancer: AUA/SUO Guideline Part II: Considerations for a Prostate Biopsy.

PURPOSE: The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer screening, biopsy, and follow-up. This is Part II of a two-part series focusing on initial and repeat biopsies, and biopsy technique. Please refer to Part I for discussion of initial prostate cancer screening recommendations. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles. RESULTS: The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsies, and biopsy technique. CONCLUSIONS: The evaluation of prostate cancer risk should be focused on the detection of clinically significant prostate cancer (Grade Group 2 or higher [GG2+]). The use of laboratory biomarkers, prostate MRI, and biopsy techniques described herein may improve detection and safety when a prostate biopsy is deemed necessary following prostate cancer screening.

Early Detection of Prostate Cancer: AUA/SUO Guideline Part I: Prostate Cancer Screening.

PURPOSE: The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer screening, biopsy, and follow-up. This is Part I of a two-part series that focuses on prostate cancer screening. Please refer to Part II for discussion of initial and repeat biopsies as well as biopsy technique. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles. RESULTS: The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsy, and biopsy technique. CONCLUSIONS: Prostate-specific antigen (PSA)-based prostate cancer screening in combination with shared decision-making (SDM) is recommended. Current data regarding risk from population-based cohorts provide a basis for longer screening intervals and tailored screening, and the use of available online risk calculators is encouraged.

NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

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. An extended Cox model allowing for the flexible modeling of identified effects via unpenalized B-splines was subsequently fit and assessed. RESULTS: The substantial improvement in model fit associated with the extended Cox approach suggests that traditional Cox proportional hazards model assumptions do not hold in this setting. Results indicate that the DRC for imatinib is non-linearly increasing, with an attenuated effect above a 74% adherence rate. The strength of this effect on remission varied over time and was strongest in the initial months of treatment, reaching a peak around 90 days post-initiation (log hazard ratio: 2.12, 95% confidence interval: 1.47 to 2.66). CONCLUSION: Most patients that achieved remission did so by 4 months (120 days) with consistently high adherence, suggesting that this could be a critical time and duration for realizing treatment benefit and patient monitoring. Findings regarding the relationship between adherence and remission can additionally help guide the design of future studies.

Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort.

BACKGROUND: Mammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis. OBJECTIVE: To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer. DESIGN: Bayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening. SETTING: Breast Cancer Surveillance Consortium (BCSC) facilities. PARTICIPANTS: Women aged 50 to 74 years at first mammography screen between 2000 and 2018. MEASUREMENTS: Screening mammograms and screen-detected or interval breast cancer. RESULTS: The cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis. LIMITATIONS: Exclusion of women with first mammography screen outside BCSC. CONCLUSION: On the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening. PRIMARY FUNDING SOURCE: National Cancer Institute.

Incorporating Baseline Breast Density When Screening Women at Average Risk for Breast Cancer : A Cost-Effectiveness Analysis.

BACKGROUND: Breast density classification is largely determined by mammography, making the timing of the first screening mammogram clinically important. OBJECTIVE: To evaluate the cost-effectiveness of breast cancer screening strategies that are stratified by breast density. DESIGN: Microsimulation model to generate the natural history of breast cancer for women with and those without dense breasts and assessment of the cost-effectiveness of strategies tailored to breast density and nontailored strategies. DATA SOURCES: Model parameters from the literature; statistical modeling; and analysis of Surveillance, Epidemiology, and End Results-Medicare data. TARGET POPULATION: Women aged 40 years or older. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: No screening; biennial or triennial mammography from age 50 to 75 years; annual mammography from age 50 to 75 years for women with dense breasts at age 50 years and biennial or triennial mammography from age 50 to 75 years for those without dense breasts at age 50 years; and annual mammography at age 40 to 75 years for women with dense breasts at age 40 years and biennial or triennial mammography at age 50 to 75 years for those without dense breasts at age 40 years. OUTCOME MEASURES: Lifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually. RESULTS OF BASE-CASE ANALYSIS: Baseline screening at age 40 years followed by annual screening at age 40 to 75 years for women with dense breasts and biennial screening at age 50 to 75 years for women without dense breasts was effective and cost-effective, yielding an incremental cost-effectiveness ratio of $36 200 per QALY versus the biennial strategy at age 50 to 75 years. RESULTS OF SENSITIVITY ANALYSIS: At a societal willingness-to-pay threshold of $100 000 per QALY, the probability that the density-stratified strategy at age 40 years was optimal was 56% compared with 6 other strategies. LIMITATION: Findings may not be generalizable outside the United States. CONCLUSION: The study findings advocate for breast density-stratified screening with baseline mammography at age 40 years. PRIMARY FUNDING SOURCE: National Cancer Institute.

Clarifying the Trade-Offs of Risk-Stratified Screening for Prostate Cancer: A Cost-Effectiveness Study.

Cancer risk prediction is necessary for precision early detection, which matches screening intensity to risk. However, practical steps for translating risk predictions to risk-stratified screening policies are not well established. We used a validated population prostate-cancer model to simulate the outcomes of strategies that increase intensity for men at high risk and reduce intensity for men at low risk. We defined risk by the Prompt Prostate Genetic Score (PGS) (Stratify Genomics, San Diego, California), a germline genetic test. We first recalibrated the model to reflect the disease incidence observed within risk strata using data from a large prevention trial where some participants were tested with Prompt PGS. We then simulated risk-stratified strategies in a population with the same risk distribution as the trial and evaluated the cost-effectiveness of risk-stratified screening versus universal (risk-agnostic) screening. Prompt PGS risk-adapted screening was more cost-effective when universal screening was conservative. Risk-stratified strategies improved outcomes at a cost of less than $100,000 per quality-adjusted life year compared with biennial screening starting at age 55 years, but risk stratification was not cost-effective compared with biennial screening starting at age 45. Heterogeneity of risk and fraction of the population within each stratum were also important determinants of cost-effectiveness.

Impact of novel systemic therapies on the first-year costs of care for melanoma among Medicare beneficiaries.

BACKGROUND: Since 2011, the therapeutic landscape of melanoma has changed dramatically because of the adoption of immune checkpoint inhibitor and targeted therapies. The authors sought to quantify the effects of these changes on short-term treatment costs by comparing the first-year cancer-attributable costs in novel (2011-2015) and historical (2004-2010) treatment eras. METHODS: The authors estimated the first-year cancer-attributable and out-of-pocket (OOP) costs by cancer stage at diagnosis by using a case-control approach. Patients aged ≥67 years with melanoma results were used to calculate the total direct costs of treatment during the first year after the diagnosis of melanoma in the US Medicare population older than 65 years. Costs were reported in 2018 dollars. RESULTS: Costs increased with the stage at diagnosis. Average first-year cancer-attributable costs per patient for stage IV patients increased significantly by 61.7% from $45,952 to $74,297 after the adoption of novel treatments. Per-patient OOP responsibility decreased by almost 30.8% across all stages of cancer but increased by 16.5% for stage IV patients from 2004 ($7646) to 2015 ($8911). The total direct cost of treatment for persons with melanoma older than 65 years increased by $16.03 million (4.93%) from $324.68 million in 2010 to $340.71 million in 2015. The largest increase in yearly total cost, $23.64 million (56.53%), was observed among stage IV patients. CONCLUSIONS: The direct cost of melanoma increased significantly in the Medicare population, particularly for advanced-stage disease. Prevention and early detection initiatives may reduce the economic burden of melanoma.

Economic Evaluation of Urine-Based or Magnetic Resonance Imaging Reflex Tests in Men With Intermediate Prostate-Specific Antigen Levels in the United States.

OBJECTIVES: For men with intermediate prostate-specific antigen (PSA) levels (4-10 ng/mL), urine-based biomarkers and multiparametric magnetic resonance imaging (MRI) are increasingly used as reflex tests before prostate biopsy. We assessed the cost effectiveness of these reflex tests in the United States. METHODS: We used an existing microsimulation model of prostate cancer (PCa) progression and survival to predict lifetime outcomes for a hypothetical cohort of 55-year-old men with intermediate PSA levels. Urine-based biomarkers-PCa antigen (PCA3), TMPRSS2:ERG gene fusion (T2:ERG), and the MyProstateScore (MPS) for any PCa and for high-grade (Gleason score ≥7) PCa (MPShg)-were generated using biomarker data from 1112 men presenting for biopsy at 10 United States institutions. MRI results were based on published sensitivity and specificity for high-grade PCa. Costs and utilities were sourced from literature and Medicare reimbursement schedules. Outcome measures included life years, quality-adjusted life years (QALYs), and lifetime medical costs per patient. Incremental cost-effectiveness ratios were empirically calculated on the basis of simulated life histories under different reflex testing strategies. RESULTS: Biopsying all men provided the most life years and QALYs, followed by reflex testing using MPShg, MPS, MRI, T2:ERG, PCA3, and biopsying no men (QALY range across strategies 15.98-16.09). Accounting for costs, MRI and MPShg were dominated by other strategies. PCA3, T2:ERG, and MPS were likely to be the most cost-effective strategy at willingness-to-pay thresholds of $100 000/QALY, $125 000/QALY, and $150 000/QALY, respectively. CONCLUSIONS: Using PCA3, T2:ERG, or MPS as reflex tests has greater economic value than MRI, biopsying all men, or biopsying no men with intermediate PSA levels.