Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening is highly effective but underused. Blood-based biomarkers (liquid biopsy) could improve screening participation. METHODS: Using our established Markov model, screening every 3 years with a blood-based test that meets minimum Centers for Medicare & Medicaid Services' thresholds (CMSmin) (CRC sensitivity 74%, specificity 90%) was compared with established alternatives. Test attributes were varied in sensitivity analyses. RESULTS: CMSmin reduced CRC incidence by 40% and CRC mortality by 52% vs no screening. These reductions were less profound than the 68%-79% and 73%-81%, respectively, achieved with multi-target stool DNA (Cologuard; Exact Sciences) every 3 years, annual fecal immunochemical testing (FIT), or colonoscopy every 10 years. Assuming the same cost as multi-target stool DNA, CMSmin cost $28,500/quality-adjusted life-year gained vs no screening, but FIT, colonoscopy, and multi-target stool DNA were less costly and more effective. CMSmin would match FIT's clinical outcomes if it achieved 1.4- to 1.8-fold FIT's participation rate. Advanced precancerous lesion (APL) sensitivity was a key determinant of a test's effectiveness. A paradigm-changing blood-based test (sensitivity >90% for CRC and 80% for APL; 90% specificity; cost ≤$120-$140) would be cost-effective vs FIT at comparable participation. CONCLUSIONS: CMSmin could contribute to CRC control by achieving screening in those who will not use established methods. Substituting blood-based testing for established effective CRC screening methods will require higher CRC and APL sensitivities that deliver programmatic benefits matching those of FIT. High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers. APL detection should not be penalized by a definition of test specificity that focuses on CRC only.

Colorectal cancer screening at age 45 years in Israel: Cost-effectiveness and global implications.

BACKGROUND: Colorectal cancer (CRC) incidence at ages <50 years is increasing worldwide. Screening initiation was lowered to 45 years in the United States. The cost-effectiveness of initiating CRC screening at 45 years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions. METHODS: A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10 years from 45 to 74 years (FIT45-74 or Colo45-74) versus from 50 to 74 years (FIT50-74 or Colo50-74). The addition of a fourth colonoscopy at 75 years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated. RESULTS: FIT50-74 and Colo50-74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45-74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45-74 versus Colo50-74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5 years earlier but mean quality-adjusted life-years gained (QALYGs) per person increased. FIT45-74 and Colo45-74 cost 23,800-53,900 new Israeli shekels (NIS)/QALYG and 110,600-162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45 years with modest participation required 19,300 additional colonoscopies in the first 3 years. CONCLUSIONS: Beginning CRC screening at 45 years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally.

Cost-Effectiveness of Earlier or More Intensive Colorectal Cancer Screening in Overweight and Obese Patients.

BACKGROUND & AIMS: Overweight and obese persons have not only elevated rates of colorectal cancer (CRC), but also higher competing mortality and healthcare spending. We examined the cost-effectiveness of intensified CRC screening in overweight and obese persons. METHODS: We adapted our validated decision analytic model of CRC screening to compare screening starting at 45 or 40 years of age instead of at 50 years of age, or shortening screening intervals, in women and men with body mass index (BMI) ranging from normal to grade III obesity. Strategies included colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual fecal immunochemical test. RESULTS: Without screening, sex-specific total CRC deaths were similar for persons with overweight or obesity I-III, reflecting the counterbalancing of higher CRC risk by lower life expectancy as BMI rises. For all BMI and sex groups, Colo10 starting at 45 years of age or FIT starting at 40 years of age were cost-effective at a threshold of $100,000 per quality-adjusted life year gained. Colo10 starting at 40 years of age was cost-effective only for men with obesity II-III, at $93,300 and $80,400 per quality-adjusted life year gained, respectively. Shifting Colo10 to earlier starting ages was always preferred over Colo5 starting at later ages. Results were robust in sensitivity analysis, including varying all-cause mortality, complication, and BMI-specific CRC risks. CONCLUSIONS: CRC screening starting at 45 years of age with colonoscopy, or at 40 years of age with FIT, appears cost-effective for women and men across the range of BMI. In men with obesity II-III, who have the highest CRC but also all-cause mortality risks, colonoscopy starting at 40 years of age appears cost-effective. It remains to be decided whether BMI should be used as a single predictor or incorporated into a multivariable tool to tailor CRC screening.

Counting Advanced Precancerous Lesions as True Positives When Determining Colorectal Cancer Screening Test Specificity.

The landmark Centers for Medicare & Medicaid Services (CMS) decision memo on blood-based biomarkers to screen for colorectal cancer (CRC) sets thresholds of 74% or higher for sensitivity and 90% or higher for specificity for CRC. This approach does not consider detection of advanced precancerous lesions as true positives. We contrasted the impact of counting advanced precancerous lesions as true vs false positives and projected CRC outcomes under contrasting tests in a validated model. A test with the threshold performance set by CMS decreased CRC incidence by 30% and CRC mortality by 48% in individuals aged 45 years. If this test also detected advanced precancerous lesions with 30% sensitivity, CRC incidence decreased by 45% and mortality by 58%, but the CRC specificity of the test of only 88% would not satisfy the CMS threshold. CMS should reconsider its definition of threshold specificity for CRC screening biomarkers. Future coverage determinations on biomarkers to screen for cancer should consider detection of relevant precursor lesions and projected outcomes.

Psychosocial outcomes following germline multigene panel testing in an ethnically and economically diverse cohort of patients.

BACKGROUND: Little is known about the psychological outcomes of germline multigene panel testing, particularly among diverse patients and those with moderate-risk pathogenic variants (PVs). METHODS: Study participants (N = 1264) were counseled and tested with a 25- or 28-gene panel and completed a 3-month postresult survey including the Multidimensional Impact of Cancer Risk Assessment (MICRA). RESULTS: The mean age was 52 years, 80% were female, and 70% had cancer; 45% were non-Hispanic White, 37% were Hispanic, 10% were Asian, 3% were Black, and 5% had another race/ethnicity. Approximately 28% had a high school education or less, and 23% were non-English-speaking. The genetic test results were as follows: 7% had a high-risk PV, 6% had a moderate-risk PV, 35% had a variant of uncertain significance (VUS), and 52% were negative. Most participants (92%) had a total MICRA score ≤ 38, which corresponded to a mean response of "never," "rarely," or only "sometimes" reacting negatively to results. A multivariate analysis found that mean total MICRA scores were significantly higher (more uncertainty/distress) among high- and moderate-risk PV carriers (29.7 and 24.8, respectively) than those with a VUS or negative results (17.4 and 16.1, respectively). Having cancer or less education was associated with a significantly higher total MICRA score; race/ethnicity was not associated with the total MICRA score. High- and moderate-risk PV carriers did not differ significantly from one another in the total MICRA score, uncertainty, distress, or positive experiences. CONCLUSIONS: In a diverse population undergoing genetic counseling and multigene panel testing for hereditary cancer risk, the psychological response corresponded to test results and showed low distress and uncertainty. Further studies are needed to assess patient understanding and subsequent cancer screening among patients from diverse backgrounds. LAY SUMMARY: Multigene panel tests for hereditary cancer have become widespread despite concerns about adverse psychological reactions among carriers of moderate-risk pathogenic variants (mutations) and among carriers of variants of uncertain significance. This large study of an ethnically and economically diverse cohort of patients undergoing panel testing found that 92% "never," "rarely," or only "sometimes" reacted negatively to results. Somewhat higher uncertainty and distress were identified among carriers of high- and moderate-risk pathogenic variants, and lower levels were identified among those with a variant of uncertain significance or a negative result. Although the psychological response corresponded to risk, reactions to testing were favorable, regardless of results.

Randomized Controlled Trial of Personalized Colorectal Cancer Risk Assessment vs Education to Promote Screening Uptake.

INTRODUCTION: Risk stratification has been proposed as a strategy to improve participation in colorectal cancer (CRC) screening, but evidence is lacking. We performed a randomized controlled trial of risk stratification using the National Cancer Institute's Colorectal Cancer Risk Assessment Tool (CCRAT) on screening intent and completion. METHODS: A total of 230 primary care patients eligible for first-time CRC screening were randomized to risk assessment via CCRAT or education control. Follow-up of screening intent and completion was performed by record review and phone at 6 and 12 months. We analyzed change in intent after intervention, time to screening, overall screening completion rates, and screening completion by CCRAT risk score tertile. RESULTS: Of the patients, 61.7% of patients were aged <60 years, 58.7% female, and 94.3% with college or higher education. Time to screening did not differ between arms (hazard ratio 0.78 [95% confidence interval (CI) 0.52-1.18], P = 0.24). At 12 months, screening completion was 38.6% with CCRAT vs 44.0% with education (odds ratio [OR] 0.80 [95% CI 0.47-1.37], P = 0.41). Changes in screening intent did not differ between the risk assessment and education arms (precontemplation to contemplation: OR 1.52 [95% CI 0.81-2.86], P = 0.19; contemplation to precontemplation: OR 1.93 [95% CI 0.45-8.34], P = 0.38). There were higher screening completion rates at 12 months in the top CCRAT risk tertile (52.6%) vs the bottom (32.4%) and middle (31.6%) tertiles (P = 0.10). DISCUSSION: CCRAT risk assessment did not increase screening participation or intent. Risk stratification might motivate persons classified as higher CRC risk to complete screening, but unintentionally discourage screening among persons not identified as higher risk.

A nationwide analysis of readmission rates after colorectal cancer surgery in the US in the Era of the Affordable Care Act.

BACKGROUND & AIMS: The Hospital Readmissions Reduction Program (HRRP), which was instituted in 2012, may have affected readmission rates for non-target conditions, including colorectal cancer (CRC). We aimed to analyze the nationwide all-cause 30-day readmission rate following CRC surgery in a US nationwide database. METHODS: We queried the 2010-2015 Nationwide Readmissions Database to estimate readmission rates. All results were weighted for national estimates. RESULTS: Among 616,348 index cases, the overall 2010-2015 30-day readmission rate was 14.7% (95% confidence interval, 14.5%-14.9% [n = 90,555]), with a decreasing trend from 15.5% in 2010 and 2011 to 13.5% in 2015 (p-trend<0.001). Rectal resection, longer length of stay, non-invasive cancer, surgery at a metropolitan teaching hospital, non-routine discharge, elective admission, and higher Elixhauser comorbidity score were associated with subsequent readmission. CONCLUSIONS: In the US, 30-day readmission rates after CRC surgery showed a decreasing trend during 2010-2015, which could represent a spillover effect of the HRRP.

Cost-Effectiveness of Current Colorectal Cancer Screening Tests.

Cost-effectiveness analysis compares benefits and costs of different interventions to inform decision makers. Alternatives are compared based on an incremental cost-effectiveness ratio reported in terms of cost per quality-adjusted life-year gained. Multiple cost-effectiveness analyses of colorectal cancer (CRC) screening have been performed. Although regional epidemiology of CRC, relevant screening strategies, regional health system, and applicable medical costs in local currencies differ by country and region, several overarching points emerge from literature on cost-effectiveness of CRC screening. Cost-effectiveness analysis informs decisions in ongoing debates, including preferred age to begin average-risk CRC screening, and implementation of CRC screening tailored to predicted CRC risk.

Strategies for Colorectal Cancer Screening.

The incidence of colorectal cancer (CRC) is increasing worldwide. CRC has high mortality when detected at advanced stages, yet it is also highly preventable. Given the difficulties in implementing major lifestyle changes or widespread primary prevention strategies to decrease CRC risk, screening is the most powerful public health tool to reduce mortality. Screening methods are effective but have limitations. Furthermore, many screen-eligible people remain unscreened. We discuss established and emerging screening methods, and potential strategies to address current limitations in CRC screening. A quantum step in CRC prevention might come with the development of new screening strategies, but great gains can be made by deploying the available CRC screening modalities in ways that optimize outcomes while making judicious use of resources.

Effectiveness and Cost of Organized Outreach for Colorectal Cancer Screening: A Randomized, Controlled Trial.

BACKGROUND: Colorectal cancer (CRC) screening remains underused, especially in safety-net systems. The objective of this study was to determine the effectiveness, costs, and cost-effectiveness of organized outreach using fecal immunochemical tests (FITs) compared with usual care. METHODS: Patients age 50-75 years eligible for CRC screening from eight participating primary care safety-net clinics were randomly assigned to outreach intervention with usual care vs usual care alone. The intervention included a mailed postcard and call, followed by a mailed FIT kit, and a reminder phone call if the FIT kit was not returned. The primary outcome was screening participation at 1 year and a microcosting analysis of the outreach activities with embedded long-term cost-effectiveness of outreach. All statistical tests were two-sided. RESULTS: A total of 5386 patients were randomly assigned to the intervention group and 5434 to usual care. FIT screening was statistically significantly higher in the intervention group than in the control group (57.9% vs 37.4%, P < .001; difference = 20.5%, 95% confidence interval = 18.6% to 22.4%). In the intervention group, FIT completion rate was higher in patients who had previously completed a FIT vs those who had not (71.9% vs 35.7%, P < .001). There was evidence of effect modification of the intervention by language, and clinic. Outreach cost approximately $23 per patient and $112 per additional patient screened. Projecting long-term outcomes, outreach was estimated to cost $9200 per quality-adjusted life-year gained vs usual care. CONCLUSION: Population-based management with organized FIT outreach statistically significantly increased CRC screening and was cost-effective in a safety-net system. The sustainability of the program and any impact of economies of scale remain to be determined.

Clinical and Economic Impact of Tailoring Screening to Predicted Colorectal Cancer Risk: A Decision Analytic Modeling Study.

BACKGROUND: Global increases in colorectal cancer risk have spurred debate about optimal use of screening resources. We explored the potential clinical and economic impact of colorectal cancer screening tailored to predicted colorectal cancer risk. METHODS: We compared screening tailored to predicted risk versus uniform screening in a validated decision analytic model, considering the average risk population's actual colorectal cancer risk distribution, and a risk-prediction tool's discriminatory ability and cost. Low, moderate, and high risk tiers were identified as colorectal cancer risk after age 50 years of ≤3%, >3 to <12%, and ≥12%, respectively, based on threshold analyses with willingness-to-pay <$50,000/quality-adjusted life-year (QALY) gained. Tailored colonoscopy (once at age 60 years for low risk, every 10 years for moderate risk, and every 5 years for high risk) was compared with colonoscopy every 10 years for all. Tailored fecal immunochemical testing (FIT)/colonoscopy (annual FIT for low and moderate risk, colonoscopy every 5 years for high risk) was compared with annual FIT for all. RESULTS: Assuming no colorectal cancer risk misclassification or risk-prediction tool costs, tailored screening was preferred over uniform screening. Tailored colonoscopy was minimally less effective than uniform colonoscopy, but saved $90,200-$889,000/QALY; tailored FIT/colonoscopy yielded more QALYs/person than annual FIT at $10,600-$60,000/QALY gained. Relatively modest colorectal cancer risk misclassification rates or risk-prediction tool costs resulted in uniform screening as the preferred approach. CONCLUSIONS: Current risk-prediction tools may not yet be accurate enough to optimize colorectal cancer screening. IMPACT: Uniform screening is likely to be preferred over tailored screening if a risk-prediction tool is associated with even modest misclassification rates or costs.

The case for philanthropic investment to increase colorectal cancer screening rates: A novel paradigm to address a public health challenge.

BACKGROUND: Colorectal cancer (CRC) remains a leading cause of cancer-related death despite being highly preventable. Efforts to increase participation in CRC screening have not met national goals. We developed a novel approach: building a business case for philanthropic investment in CRC screening. METHODS: A taskforce representing the public health community, professional societies, charitable foundations, academia, and industry was assembled to: (a) quantify the impact of improving CRC screening rates; (b) identify barriers to screening; (c) estimate the "activation cost" to overcome barriers and screen one additional person; (d) develop a holistic business case that is attractive to philanthropists; and (e) launch a demonstration project. RESULTS: We estimated that of 50 600 CRC deaths annually in the US, 55% occur in 50- to 85-year-olds and are potentially addressable by improvements in CRC screening. Barriers to screening were identified in all patient journey phases, including lack of awareness or insurance and logistical challenges in the pre-physician phase. The cost to activate one person to undergo screening was $25-175. This translated into a cost of $6000-36 000 per CRC death averted by philanthropic investment. Based on this work, the Colorectal Cancer Alliance launched the effort "March Forth" to prevent 100 000 CRC deaths in the US over 10 years, with the first pilot in Philadelphia. CONCLUSIONS: A holistic business plan can attract philanthropy to promote CRC screening. A simple message of "You can save a life from CRC with a $25 000 donation" can motivate demonstration projects in regions with high CRC rates and low screening participation.

High-Intensity Versus Low-Intensity Surveillance for Patients With Colorectal Adenomas: A Cost-Effectiveness Analysis.

Background: Surveillance of patients with colorectal adenomas has limited long-term evidence to support current practice. Objective: To compare the lifetime benefits and costs of high- versus low-intensity surveillance. Design: Microsimulation model. Data Sources: U.S. cancer registry, cost data, and published literature. Target Population: U.S. patients aged 50, 60, or 70 years with low-risk adenomas (LRAs) (1 to 2 small adenomas) or high-risk adenomas (HRAs) (3 to 10 small adenomas or ≥1 large adenoma) removed after screening with colonoscopy or fecal immunochemical testing (FIT). Time Horizon: Lifetime. Perspective: Societal. Intervention: No further screening or surveillance, routine screening after 10 years, low-intensity surveillance (10 years after LRA removal and 5 years after HRA removal), and high-intensity surveillance (5 years after LRA removal and 3 years after HRA removal). Outcome Measures: Colorectal cancer (CRC) incidence and incremental cost-effectiveness. Results of Base-Case Analysis: Without surveillance or screening, lifetime CRC incidence for patients aged 50 years was 10.9% after LRA removal and 17.2% after HRA removal at screening colonoscopy. Subsequent colonoscopic screening, low-intensity surveillance, or high-intensity surveillance decreased incidence by 39%, 46% to 48%, and 55% to 56%, respectively. Incidence of CRC and surveillance benefits were higher for adenomas detected at FIT screening and lower for older patients. High-intensity surveillance cost less than $30 000 per quality-adjusted life-year (QALY) gained compared with low-intensity surveillance. Results of Sensitivity Analysis: High-intensity surveillance cost less than $100 000 per QALY gained in most alternative scenarios for adenoma recurrence, CRC incidence, longevity, quality of life, screening ages, surveillance ages, test performance, disutilities, and cost. Limitation: Few surveillance outcome data exist. Conclusion: The model suggests that high-intensity surveillance as recommended in the United States provides modest but clinically relevant benefits over low-intensity surveillance at acceptable cost. Primary Funding Source: National Cancer Institute.

Cost-Effectiveness and National Effects of Initiating Colorectal Cancer Screening for Average-Risk Persons at Age 45 Years Instead of 50 Years.

BACKGROUND & AIMS: The American Cancer Society has recommended initiating colorectal cancer (CRC) screening at age 45 years instead of 50 years. We estimated the cost effectiveness and national effects of adopting this recommendation. METHODS: We compared screening strategies and alternative resource allocations in a validated Markov model. We based national projections on screening participation rates by age and census data. RESULTS: Screening colonoscopy initiation at age 45 years instead of 50 years in 1000 persons averted 4 CRCs and 2 CRC deaths, gained 14 quality-adjusted life-years (QALYs), cost $33,900/QALY gained, and required 758 additional colonoscopies. These 758 colonoscopies could instead be used to screen 231 currently unscreened 55-year-old persons or 342 currently unscreened 65-year-old persons, through age 75 years. These alternatives averted 13-14 CRC cases and 6-7 CRC deaths and gained 27-28 discounted QALYs while saving $163,700-$445,800. Improving colonoscopy completion rates after abnormal results from a fecal immunochemical test yielded greater benefits and savings. Initiation of fecal immunochemical testing at age 45 years instead of 50 years cost $7700/QALY gained. Shifting current age-specific screening rates to 5 years earlier could avert 29,400 CRC cases and 11,100 CRC deaths over the next 5 years but would require 10.7 million additional colonoscopies and cost an incremental $10.4 billion. Improving screening rates to 80% in persons who are 50-75 years old would avert nearly 3-fold more CRC deaths at one third the incremental cost. CONCLUSIONS: In a Markov model analysis, we found that starting CRC screening at age 45 years is likely to be cost effective. However, greater benefit, at lower cost, could be achieved by increasing participation rates for unscreened older and higher-risk persons.

Contrasting Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening Under Commercial Insurance vs. Medicare.

OBJECTIVES: Most cost-effectiveness analyses of colorectal cancer (CRC) screening assume Medicare payment rates and a lifetime horizon. Our aims were to examine the implications of differential payment levels and time horizons for commercial insurers vs. Medicare on the cost-effectiveness of CRC screening. METHODS: We used our validated Markov cohort simulation of CRC screening in the average risk US population to examine CRC screening at ages 50-64 under commercial insurance, and at ages 65-80 under Medicare, using a health-care sector perspective. Model outcomes included discounted quality-adjusted life-years (QALYs) and costs per person, and incremental cost/QALY gained. RESULTS: Lifetime costs/person were 20-44% higher when assuming commercial payment rates rather than Medicare rates for people under 65. Most of the substantial clinical benefit of screening at ages 50-64 was realized at ages ≥65. For commercial payers with a time horizon of ages 50-64, fecal occult blood testing (FOBT) and fecal immunochemical testing (FIT) were cost-effective (<$61,000/QALY gained), but colonoscopy was costly (>$185,000/QALY gained). Medicare experienced substantial clinical benefits and cost-savings from screening done at ages <65, even if screening was not continued. Among those previously screened, continuing FOBT and FIT under Medicare was cost-saving and continuing colonoscopy was highly cost-effective (<$30,000/QALY gained), and initiating any screening in those previously unscreened was highly effective and cost-saving. CONCLUSIONS: Modeling suggests that CRC screening is highly cost-effective over a lifetime even when considering higher payment rates by commercial payers vs. Medicare. Screening may appear relatively costly for commercial payers if only a time horizon of ages 50-64 is considered, but it is predicted to yield substantial clinical and economic benefits that accrue primarily at ages ≥65 under Medicare.

Racial and Ethnic Disparities in Cancer Survival: The Contribution of Tumor, Sociodemographic, Institutional, and Neighborhood Characteristics.

Purpose Racial/ethnic disparities in cancer survival in the United States are well documented, but the underlying causes are not well understood. We quantified the contribution of tumor, treatment, hospital, sociodemographic, and neighborhood factors to racial/ethnic survival disparities in California. Materials and Methods California Cancer Registry data were used to estimate population-based cancer-specific survival for patients diagnosed with breast, prostate, colorectal, or lung cancer between 2000 and 2013 for each racial/ethnic group (non-Hispanic black, Hispanic, Asian American and Pacific Islander, and separately each for Chinese, Japanese, and Filipino) compared with non-Hispanic whites. The percentage contribution of factors to overall racial/ethnic survival disparities was estimated from a sequence of multivariable Cox proportional hazards models. Results In baseline models, black patients had the lowest survival for all cancer sites, and Asian American and Pacific Islander patients had the highest, compared with whites. Mediation analyses suggested that stage at diagnosis had the greatest influence on overall racial/ethnic survival disparities accounting for 24% of disparities in breast cancer, 24% in prostate cancer, and 16% to 30% in colorectal cancer. Neighborhood socioeconomic status was an important factor in all cancers, but only for black and Hispanic patients. The influence of marital status on racial/ethnic disparities was stronger in men than in women. Adjustment for all covariables explained approximately half of the overall survival disparities in breast, prostate, and colorectal cancer, but it explained only 15% to 40% of disparities in lung cancer. Conclusion Overall reductions in racial/ethnic survival disparities were driven largely by reductions for black compared with white patients. Stage at diagnosis had the largest effect on racial/ethnic survival disparities, but earlier detection would not entirely eliminate them. The influences of neighborhood socioeconomic status and marital status suggest that social determinants, support mechanisms, and access to health care are important contributing factors.