Educational Objectives
•Discuss socioeconomic, racial, ethnic, and cultural barriers to preventive cancer screening for underserved populations and how to reduce them
•Characterize the role of blood-based cancer screening in early cancer detection, including recent clinical trial and real-world data on available and emerging blood-based multi-cancer early detection (MCED) screening tests
•Describe strategies to introduce MCED screening into clinical practice, including patient eligibility criteria and shared decision-making
•Educate patients on the cancer screening initiatives available to underserved populations, including potential participation in clinical trials designed to make access to cancer screening equitable
The State of Cancer Screening in the US and Locally
The 2nd Leading Cause of Death in the US1 will be diagnosed with cancer in their lifetime.2 are not up to date on at least 1 routine cancer screening.3,a
Death Rates (All Sites), by Race and Ethnicity1 (2016-2020) 5-Year Relative Survival, by Race and Site2 (2014-2020)
Setting: Bronx, NY
Single-person households
lang, language.
New York University Furman Center. https://furmancenter.org/neighborhoods/view/the-bronx#demographics; Statistical Atlas. https://statisticalatlas.com/county/NewYork/Bronx-County/Ancestry; US Census Bureau. www.census.gov/quickfacts/fact/table/bronxcountynewyork/PST045223.
Bronx Is the Last of 62 NY Counties in Health Factors
High rates of:
Obesity
Food insecurity
Houselessness
Population density
Air pollution
Crime
Limited green space
Sedentary lifestyle NY, New York. University of Wisconsin Population Health Institute County Health Rankings & Roadmaps. https://www.countyhealthrankings.org/health-data/new-york/bronx?year=2024; The Institute for Family Health. https://institute.org/not62/.
Cancer Incidence and Mortality in NY
USPSTF Recommendations for Screening Asymptomatic Patients
Cancer
Screening Criteria
Breast Biennial screening mammography
• Cervical cytology every 3 years
Cervical
Colorectal
• Cervical cytology every 3 years OR
• hrHPV every 5 years OR
• hrHPV + cervical cytology every 5 years
• Stool-based testing
– Annual FIT or high-sensitivity guaiac-based testing
– sDNA-FIT every 1-3 years
• Colonoscopy every 10 years
• CT colonography every 5 years
• Flexible sigmoidoscopy
– Every 5 years
– Every 10 years + annual FIT
Lung Annual LDCT
Prostate PSA testing
Women aged 40-74 years
Women aged 21-29 years
Women aged 30-65 years
2024
2018; update in progress
• All aged 45-75 years
• Certain populations aged 76-85 years
2021
All aged 50-80 years and ≥20 pack year history of smoking and currently smoke or quit within the past 15 years
Men aged 55-69 years when elected with shared decision-making
2021
2018; update in progress
The USPSTF currently recommends AGAINST screening asymptomatic patients for ovarian, pancreatic, testicular, and thyroid cancers (estimated to account for 11% of all cancer deaths in 2024).3,4
CT, computed tomography; FIT, fecal immunochemical test; hrHPV, high-risk human papillomavirus; LDCT, low-dose computed tomography; PSA, prostate-specific antigen; sDNA-FIT, stool DNA test with FIT; USPSTF, United States Preventive Services Task Force. 1. USPSTF. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation-topics/uspstf-a-and-b-recommendations; 2. USPSTF. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/prostate-cancer-screening; 3. NCI SEER. https://seer.cancer.gov/statfacts; 4. USPSTF. www.uspreventiveservicestaskforce.org/uspstf/recommendation-topics.
Cancer Screening Successes
BREAST CANCER
Since its peak in 1989, female screening resulted in a 20% in overall mortality1
Beau AB, et al. J Clin Oncol. 2018;36(30):2988-2994; 2. Pastorino U, et al. Ann Oncol. 2019;30(7):1162-1169.
LUNG CANCER
Early diagnosis mortality rates at 10 years by 39% compared with no intervention2
1.
Cancer Screening Limitations
More than half of cancer-related deaths result from cancers that do not have USPSTF guideline–recommended screenings Estimated Deaths (2024)1,a
One recent study estimated that 68.6% of cancer deaths in the US are from cancer types not eligible for USPSTF-recommended screening.2
Cancer Screening
Suboptimal Adherence Rates in the US (2021)1
N/A, not available. a2020; bIndividuals aged 55 to 80 years who currently or formerly smoked cigarettes and quit within the past 15 years, with ≥30 pack-year smoking history. 1. ACS. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-prevention-and-early-detection-facts-and-figures/2024-cped-files/cped2024-cff.pdf; 2. Guerra CE, et al. Annu Rev Med. 2024;75:67-81.
Cancer Detection at Earlier Stage Reduces Mortality
Regardless of Ethnicity and Sex
•Similar percentage reductions would be seen across all races and both sexes by replacing metastatic outcomes with those of earlier stagesa
with Stage IV to III
with Stage IV to III/II/I
Recognizing and Addressing Real-World Barriers to Cancer Screening
Disparities in Cancer Screening
Screening disparities exist for racial and ethnic minorities, the uninsured, and individuals who live below the national poverty line.1-4
Adults (aged 50-75 years) who were up to date with colorectal screening, by poverty income level6
aNon-Hispanic patients.
1. American Association for Cancer Research (AACR). https://cancerprogressreport.aacr.org/disparities/chd20-contents/chd20-disparities-in-cancer-screening-for-earlydetection/; 2. Liu D, et al. J Racial Ethn Health Disparities. 2021;8(1):107-126; 3. Alyabsi M, et al. Front Public Health. 2020;8:532950; 4. Koc H, et al. Int J Environ Res Public Health. 2018;15(9):1961; 5. Jemal A, et al. J Natl Cancer Inst. 2017;109(9):djx030; 6. NCI. https://progressreport.cancer.gov/detection/colorectal_cancer.
Cancer
by Race/Ethnicity
Timely Colonoscopy Screening in NYC and the Bronx
Prevalence of timely colonoscopya among adults aged ≥50 years, by raceb and ethnicity, NYC, 20181
Barriers to Colonoscopy Screening for Patients in the Bronx2,c
Barriers to Cancer Screening Tests
Patient
• Socioeconomic status (SES)
• Awareness & knowledge
• Beliefs & attitudes, including fatalism, fear, stigma, inaccurate perceptions of risk, etc
• Language
• Health literacy
• Trust
• Health insurance
• Access to primary care
• Transportation
• Out-of-pocket costs
• Conflicts with work & life demands
• Caregiver support
Policy
• Medicaid expansion
Institutional Provider
Patient
CDC, Centers for Disease Control and Prevention. MacKinnon K, et al. Cancer. 2023;129(S19):3152-3161.
• CDC’s Breast and Cervical Cancer Early Detection Program
Institutional
• Segregation of cancer screening resources
• Reminder systems
• Interpreters
• Patient navigators
• Community outreach, education, & engagement
• Perceived trustworthiness Policy
Provider
• Knowledge of cancer screening guidelines
• Time constraints
• Cultural humility
• Communication skills
• Office team support
• Unconscious bias
How to Address the Barriers
Patient Level Provider Level
•Provide materials/resources in multiple languages
•Utilize motivational interviewing
•Minimize medical mistrust
•Implement a trauma-informed care approach
•Have conversations with all eligible patients
•Do not make assumptions about patient interest or ability to undergo cancer screening
Montefiore Community Resources
Bridging the Gap Between Available Resources and Patient Engagement to Increase Cancer Screening Adherence
• Education and Free Screening: MECCC offers multiple events throughout the year for breast, cervical, lung, prostate, colorectal, and skin cancers
• Patient Navigation: BOLD Cancer Screening Navigation Helpline offers multilingual lay navigators to help non–English speaking individuals navigate through the screening process from diagnosis to treatment – 718-430-3613; cancerscreening@einsteinmed.edu
• Peer Support: Cancer “Screening Companions” (BOLD Buddies) are volunteers who support anyone with barriers that might keep them from undergoing cancer screening and follow-up testing
MCED Tests
What Are They and Where Do They Fit for Our Patients?
a
Many
Cancers May Be Missed With Conventional Screening1,a
•Current paradigm for cancer screening is “1 organ at a time”2
•68% of cancers found in participants in the National Lung Screening Trial (NLST) were NOT lung cancer3,e
cfDNA
The Basis for New, Minimally Invasive Screening Modalities
Apoptosis
Necrosis
Secretion
Apoptotic bodies
Point mutations
Wan JCM, et al. Nat Rev Cancer. 2017;17(4):223-238; 2. Cisneros-Villanueva M, et al. Br J Cancer. 2022;126(3):391-400.
Copy number alterations
Exosomal DNA
Rearrangements
cfDNA anomalies that can be measured and characterized in assays1,2
Methylation changes
DNA Methylation as a Tumor Biomarker
• Cancer is associated with epigenetic changes (eg, DNA methylation) that can alter:
– The 3-dimensional conformation of the genome
– Protein-DNAinteractions
– Expression patterns (silencing, activation)
• Changes in DNA methylation patterns:
– Can contribute to tumorigenesis or progression
•ctDNA
– Can be identified and characterized via nextgeneration sequencing + machine learning
ctDNA, circulating tumor DNA; Me, methylation. Locke WJ, et al. Front Genet. 2019;10:1150.
Multi-Cancer Early Detection (MCED) Tests That Have Received FDA Breakthrough Device Designationa
MCED tests screen for multiple types of cancer in one test.
OverC MCDBT2,5
▪ 5+ cancers
▪ Deep methylation sequencing
Protein biomarkers
CancerSEEK1,2
▪ 8 cancers
▪ Methylated cfDNA (16 genes) + protein biomarkers
Galleri1,2
▪ >50 cancers
▪ >100,000 differentially methylated regions
cfDNA biomarkers
cfDNA, cell-free DNA; FDA, US Food and Drug Administration; MCDBT, multi-cancer detection blood test.
CanScan3,4 ▪ 13+ cancers
▪ Genome-wide fragmentomicsrelated features
aAs of September 2024, Galleri is the only commercially available test in the US that analyzes cfDNA methylation patterns. 1. Hackshaw A, et al. Cancer Cell. 2022;40(2):109-113; 2. Liu MC. Br J Cancer. 2021;124(9):1475-1477; 3. Yang S, et al. Cancer Res. 2024;84(suppl 6):1263; 4. PR Newswire. January 3, 2024. https://www.prnewswire.com/news-releases/fda-grants-breakthrough-device-designation-for-geneseeqs-multi-cancer-early-detection-solution302024692.html; 5. Gao Q, et al. J Clin Oncol. 2021;39(suppl 3):459.
Differentiating Available Cancer Screening vs Cancer Risk Tests
•MCED Testing is SCREENING for multiple cancers (eg, Galleri, CancerGuard)
•Genetic Testing is RISK CALCULATION (eg, OneTest, BRCA1/2 testing)
•Tumor Genetic Profiling is GENOMIC ANALYSIS of TUMOR CELL
MUTATIONS
in order to guide treatment (eg, Oncotype Dx, KRAS)
Assay Validation Criteria
Specificity
the test’s ability to detect a true negative (eg, a patient who does not have that particular cancer)
Negative Predictive Value (NPV)
percentage of all negative samples that are true negatives
Sensitivity
the test’s ability to detect a true-positive sample (eg, a patient with a particular cancer)
Examples
97% Sensitivity would produce 3 false-negative results for every 100 samples from patients with cancer.
Positive Predictive Value (PPV)
assessment of the utility of the test in clinical practice, measured as the percentage of all positive samples that are true positives
97% Specificity would result in 3 false-positive signals for every 100 samples from patients with no cancer.
Criteria Important for a Cancer Screening Test
Criteria Why Important
High specificity
To minimize false positives and thereby reduce unnecessary workup, overdiagnosis, and overtreatment
High sensitivity To detect early tumors that may be curable by surgery
High PPV To reduce unnecessary workup, overdiagnosis, overtreatment
High NPV To reduce the probability of missing potentially curable tumors
Ability to localize site of tumor
To minimize imaging for localizing tumor site and cancer signal tissue of origin (CSO)
Duffy MJ, et al. Clin Chem Lab Med. 2021;59(8):1353-1361.
Clinical Trial Data for Available and Investigational MCED Tests
Thunder II4,e validation set
5,f
Real-world experience6,g
CSO, cancer signal origin. aN=10,006 women with no prior cancer history; bN=6578 patients aged ≥50 years with or without additional risk factors for cancer (smoking history, genetic predisposition, or prior diagnosis of successfully treated cancer); cSensitivity determined from the CCGA study; dN=5461 symptomatic individuals aged ≥18 years referred for urgent investigation for a possible gynecologic, lung, or gastrointestinal cancer or referred to a rapid diagnostic center with nonspecific symptoms that might be due to cancer; eN=639 (with cancer=351) + (noncancer=288); fN=3724 participants aged between 45 and 75 years without cancer-related symptoms; gN=53,744 MCED tests delivered. 1. Lennon AM, et al. Science. 2020;369(6499):eabb9601; 2. Schrag D, et al. Lancet. 2023;402(10409):1251-1260; 3. Nicholson BD, et al.
4. Gao Q, et al. J Clin Oncol. 2021;39(suppl 3):459; 5. Yang S, et al. Cancer Res. 2024;84(suppl 6):1263; 6. Westgate C, et al. J Clin Oncol. 2023;41(suppl 16):10519. Trial Test Specificity
What We’ve Learned About cfDNA-Based MCEDs So Far Compared to Traditional Screening Modalities
Meta-analyses
FNR, false-negative rate; FPR, false-positive rate. aThe 10-year cumulative probability of at least 1 false-positive result for recall; bThe meta-analyses presented included 10/12 cfDNA-based MCED tests.7,8
1. Lehman CD, et al. Radiology. 2017;283(1):49-58; 2. Ho TH, et al. JAMA Netw Open. 2022;5(3):e222440; 3. The National Lung Screening Trial (NLST) Research Team. N Engl J Med. 2013;368(21):1980-1991; 4. NLST Research Team. N Engl J Med. 2011;365(5):395-409; 5. Vahedpoor Z, et al. Taiwan J Obstet Gynecol. 2019;58(3):345-348; 6. Park JH, et al. J Clin Oncol. 2023;41(suppl 16):3069; 7. Park JH, et al. Cancer
Modeling Data Demonstrate That the Addition of MCED Testing to Routine Cancer Screening Could Result in:
• 3× as many cancers diagnosed as routine screening alone, including identification of1,a:
– An additional 11% of breast cancer cases2
– Up to 58% of unscreened cancers that are the leading causes of cancer death2
• ≥17% fewer cancer deaths per year1,a
aAmong individuals aged 50-79 years who have been screened. 1. Sasieni P, et al. Br J Cancer. 2023;129(1):72-80; 2. Hathaway C, et al. Front Oncol. 2021;11:688455.
Adding MCED to Recommended Screening Could Be More Cost-Effective When Diagnosing Cancer
Current Screening (67M) With Added MCED Screeninga Total diagnostic costs
aEstimated.
Hackshaw A, et al. Br J Cancer. 2021;125(10):1432-1442.
How Will MCED Tests Impact Cancer Disparities?
•Blood-based MCED tests may
–Mitigate racial/ethnic cancer disparities if offered in collaboration with guideline-recommended cancer screening to detect aggressive tumors that are diagnosed in minorities at higher rates than in the general population
–Widen racial/ethnic cancer disparities if
•MCED test adoption is lower in minority communities, or if insurance coverage is limited, then blood-based MCED testing could disproportionately benefit White patients and increase rather than reduce racial disparities in early cancer detection
•If MCED-positive patients do not have equitable access to diagnostic workups, or adherence rates differ by race and ethnicity, disparities will increase
Ward AS, et al. https://healthpolicy.usc.edu/research/reducing-racial-disparities-in-early-cancer-diagnosis-with-blood-based-tests/.
Clinical Trials and Initiatives That Are Currently Enrolling1 •CancerGUARD (formerly CancerSEEK): Falcon Registry Real-World Evidence2 •GALLERI: REACH, REFLECTION •OverC MCDBT: PREVENT •HarbingerHx: CORE-HH •PanSeerX: FuSion Project •CanScana: JINLING
aAwarded FDA Breakthrough Device Designation in January 2024. 1. ClinicalTrials.gov. https://clinicaltrials.gov/; 2. Genomeweb. https://www.genomeweb.com/molecular-diagnostics/exact-sciences-enrolls-first-patient-multi-cancer-earlydetection-study.
Eligibility Criteria
Who Is Eligible?
• Age ≥50 years
• Family or personal history of cancer
• Known genetic mutations
Who Is NOT Eligible?
• Pediatric populations (age <21 years)
• Pregnant patients
• Patients with active cancer diagnosis or treated for cancer in last 3 years
Risk Factors
•Alcohol use
•Exposure to cancer-causing substances (eg, fire smoke, tobacco smoke, radiation, sunlight)
•Immunosuppression
•Infectious agents (eg, viruses, parasites)
•Overweight/Obesity
•Tobacco use
MCED testing should be used to complement recommended screening approaches to identify cancers they do not cover, NOT in place of current screening.
Considerations When Discussing MCED With Patients1-3
Potential Advantages
Increased and earlier cancer detection rate, including asymptomatic patients
Trials demonstrate improving efficiency of testing, with increased PPV, decreased NNS
Screening of organ sites currently without a screening modality
Screening for multiple cancers at the same time
Less-invasive procedures and potentially improved success of treatments
May help reduce health care disparities by increasing participation rates through improved access to screening
Potential Disadvantages
Currently not covered by most insurance (commercial or government sponsored)
“No cancer detected” does not rule out future cancer diagnosis. Sensitivity limited
Consequential cancers found sooner, but patient may not live any longer
Possible harm from unnecessary diagnostic procedures due to false positives or missed diagnoses due to false negatives
Overdiagnosis and overtreatment of cancers that would have otherwise never bothered the patient
Inequities will increase if tests are not widely available, affordable, and acceptable to minority groups
1. Klein EA, et al. Ann Oncol. 2021;32(9):1167-1177; 2. MCED Consortium. https://static1.squarespace.com/static/615c87aaea640d19cc98840b/t/6499fcaddf755715cc844f39/1687813293969/MCED+Consortium+Care+Delivery+Paper_Final.pdf; 3. Welch HG, Kramer B. STAT. January 12, 2022. www.statnews.com/2022/01/12/medicare-shouldnt-cover-liquid-biopsies-early-cancer-detection/.
Accessibility of MCED Testing
• Currently covered by only a few health and life insurance companies1
– Out-of-pocket cost for Galleri is $949; HSA/FSA eligible
• Medicare Multi-Cancer Early Detection Screening Coverage Act: originally introduced 2021, reintroduced March 2023 (House of Representatives) and June (Senate) 20232,3
– Not passed yet
• Cancer Moonshot Initiative: develop plans to quickly evaluate utility and benefits of MCED tests4
– Early 2022, added goal of reducing cancer death rate by half within 25 years and improving lives of people with cancer and cancer survivors
• NCI Vanguard Study on Multi-Cancer Detection evaluating MCED assays for purpose of cancer screening
1. Healthline. https://www.healthline.com/health/cancer/galleri-cancer-test#cost-and-insurance; 2. Prevent Cancer Foundation. https://www.preventcancer.org/multi-cancerearly-detection/coverage-and-legislation/#coverage-act; 3. Congress.gov. https://www.congress.gov/bill/118th-congress/senate-bill/2085; 4. AACR. Cancer Discov. 2022;12(4):876.
REACH Initiative
(Real-world Evidence to Advance Multi-Cancer Early Detection Health Equity)
•Medicare coverage for Galleri testing and follow-up diagnostic services for 50,000 Medicare beneficiaries
•Goal: evaluate the clinical impact of multi-cancer screening in underserved populations (including racial and ethnic minorities, seniors from historically underserved communities)
•Initiated in late 2023
Grail. July 18, 2024. https://grail.com/press-releases/grail-announces-first-participant-enrolled-in-reach-study-evaluating-clinical-impact-of-galleri-multi-cancer-earlydetection-mced-test-in-the-medicare-population/.
Potential Workflow for MCED Testing
Pilot Implementation in Mercy Health Systema
3 Patient blood sample sent to test manufacturer
Results delivered via portal within 2 weeks of sample receipt by lab Patient Notification 4 “No Cancer Signal Detected” Patient notified and additional health screenings discussed as needed “Cancer Signal Detected”
Diagnostic results and next steps discussed with patient
cancer signal detected. aN=925 MCED test orders (from 3777 total referrals: 2931 patient, 846 provider).
G, et al. J Clin Oncol. 2023;41(suppl 16):1526.
Median time from CSD result to:
•Patient notification of result: 22.8 hours
•Initial diagnostic evaluation: 3.1 days
•Cancer diagnosis (6/925): 8.7 days
•Initiation of treatment or first postdiagnosis specialist visit: 33 days
Suggested Initial Diagnostic Steps
Following a “Signal Detected” Result
CSO Prediction
Multiple myeloma
Upper GI (esophagus, stomach)
1
Proposed First-Line Procedures
Blood workup including peripheral blood smear, CBC with differential; chemistry tests including creatinine clearance, protein electrophoresis of blood/urine
Endoscopy
Colorectal Colonoscopy
Head and neck Physical exam, fiber optic exam, U/S, CT or MRI with contrast, PET-CT2
Pancreas, gallbladder CT abdomen with IV contrast, MRCP, GI referral
Ovary CA-125 analysis3, abdominal/pelvic exam, U/S (preferred)
Blood work
Lung CT chest with or without IV contrast
Liver, bile duct U/S, CT, GI referral
Breast Diagnostic mammography with U/S (MRI if mammography screening within last 3 months)
Lymphoid neoplasm CT (neck, chest, abdomen, pelvis) with IV contrast, PET-CT
Indeterminate CT (neck, chest, abdomen, pelvis) with IV contrast, PET-CT For your reference, this chart is
CBC, complete blood count; IV, intravenous; MRCP, magnetic resonance cholangiopancreatography; PET, positron emission tomography. 1. Adapted from Nadauld LD, et al. Cancers (Basel). 2021;13(14):3501; 2. Fearington FW, et al. Oral Oncol. 2024;152:106809; 3. Funston G, et al. PLoS Med. 2020;17:e1003295.
Conclusions
• Cancer screening disparities are significant
– Low adherence rates among racial and ethnic minorities, uninsured, and individuals living below the national poverty line
• Strategies to reduce disparities include free community screening events, appropriate patient conversations and materials, and institutional programs such as BOLD
• MCED tests have demonstrated the ability to detect cancer signals and their point of origin
– Potential to increase cure rates and reduce morbidity and mortality associated with cancer
• MCED tests are intended to be used in conjunction with current cancer screening strategies, not to replace them
– Barriers to their incorporation into everyday practice include lack of guidelines, organizational recommendations, and insurance coverage
• Strategies to reduce barriers to cancer screening on a patient, provider, and institutional level are essential