Learning Objectives
• Describe the role of blood-based cancer screening in addressing the limitations of current guideline-recommended screening modalities and improving early cancer detection rates
• Explain the use of methylated cell-free DNA (cfDNA) for the early detection of various cancer types and their tissue of origin
• Discuss recent clinical trial and real-world data on available and emerging blood-based multi-cancer early detection (MCED) screening tests
• Recognize eligibility criteria for MCED testing and appropriate follow-up pathways should a patient receive a “cancer signal detected” result
THE BURDENS OF CANCER IN THE US
The
Second Leading Cause of Death in the US 1 will be diagnosed with cancer in their lifetime.2 are not up to date on at least 1 routine cancer screening.3,a
It is estimated that >2 million new cancer cases will be diagnosed and >611,000 lives lost to cancer in 2024.4 %~40 70%
aN=7004 individuals aged ≥21 years. The cancer screenings included in this survey were breast, cervical, colorectal, lung, oral, prostate, skin, and testicular. 1. Murphy SL, et al. NCHS Data Brief. 2021;427:1-8; 2. National Cancer Institute (NCI). Accessed May 13, 2024. https://www.cancer.gov/about-cancer/understanding/statistics; 3. Prevent Cancer Foundation. Accessed September 16, 2024. https://www.preventcancer.org/early-cancer-detection-better-outcomes/2024-early-detection-survey-prevent-cancerfoundation/#results; 4. National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program. Accessed May 13, 2024. https://seer.cancer.gov/statfacts/html/all.html.
Why Are People Behind on Routine Preventive Cancer Screenings?
Other reasons include:
1. Skepticism of health care system
2. Nervousness about the screening examination
3. Inability to afford cost of screening
More Than Half of Cancer Deaths in the US Are Due to Cancers Ineligible for USPSTF-Recommended Screening
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 USPSTFrecommended screening.2
Cancer Detection at Earlier Stage Would Reduce Mortality Regardless of Ethnicity and Sex
• Similar relative percentage reductions would be seen across all races and both sexes by replacing metastatic outcomes with those of earlier stages:
with Stage IV to III
~21% with Stage IV to III/II/I
USPSTF Recommendations for Screening Asymptomatic Patients
Cancer Screening Criteria
Breast1 Biennial screening mammography
• Cervical cytology every 3 years
Cervical1
Colorectal1
• 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
Lung1 Annual LDCT
Prostate2 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 per 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
CT, computed tomography; FIT, fecal immunochemical test; hrHPV, high-risk human papillomavirus; LDCT, low-dose CT; PSA, prostate-specific antigen; sDNA-FIT, stool DNA test with FIT.
1. USPSTF. Accessed May 16, 2024. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation-topics/uspstf-a-and-b-recommendations;
2. USPSTF. Accessed May 16, 2024. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/prostate-cancer-screening.
USPSTF Recommendations
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).1,2
NCI SEER. Accessed May 21, 2024. https://seer.cancer.gov/statfacts; USPSTF. Accessed May 21, 2024. www.uspreventiveservicestaskforce.org/uspstf/recommendation-topics.
Cancer Screening Successes
in Age-Adjusted Mortality Rates,
BREAST CANCER
1.2% annually1
Since its peak in 1989, screening has resulted in a 20% in overall mortality2
1.7% annually1
4.1% annually1 Early diagnosis mortality rates at 10 years by 39% compared with no intervention3
Disparities in 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 (2000-2021), by5:
of
aNon-Hispanic patients.
1. American Association for Cancer Research (AACR). Accessed August 7, 2024. https://cancerprogressreport.aacr.org/disparities/chd20-
for-early-detection/; 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
Health. 2018;15(9):1961; 5. NCI. Accessed August 7, 2024. https://progressreport.cancer.gov/detection/colorectal_cancer; 6. Jemal A, et al. J Natl Cancer Inst. 2017;109(9):djx030. Risk of death compared with White patients6: 33% higher for Blacka patients, 51% higher for Indigenous Americana patients
Cancer Screening Limitations
Many Cancers Are Not Detected by a Preventive Screening Test
• Current screening recommendation is “one organ at a time”1
• 68% of cancers found in participants in the National Lung Screening Trial (NLST) were NOT lung cancer2,a
Diagnosed cancers with no preventive screening test
Cancers3
aN=53,299 people in the US; non-lung cancers were identified based on patient self-report or death certificates.
Cancers detected via conventional screening
Screenable cancers not detected by screening
1. Ahlquist DA. NPJ Precis Oncol. 2018;2:23; 2. Chang ET, et al. J Clin Oncol. 2023;41(suppl 16):10633; 3. NORC at the University of Chicago. Accessed September 16, 2024. https://www.norc.org/PDFs/GRAIL/State-Specific%20PCDSs%20chart%201213.pdf.
MCED Testing Could Detect Cancers Missed
by Traditional Single-Organ Screening Modalities
The Power of Aggregate Prevalence for Selected Cancers
aTo detect 1 cancer.
gastrointestinal; NNS, number needed to screen; PPV, positive predictive value. Ahlquist DA. NPJ Precis Oncol. 2018;2:23.
MCED Assays That Have Received FDA Breakthrough Device Designationa
OverC MCDBT2,5
5+ cancers
Deep methylation sequencing
Galleri1,2
>50 cancers
>100,000 differentially methylated regions
CancerSEEK1,2 8 cancers Methylated cfDNA (16 genes) + protein biomarkers
CanScan3,4
cfDNA biomarkers
aAs of August 2024, Galleri is the only commercially available test in the US that analyzes cfDNA methylation patterns. cfDNA, cell-free DNA; FDA, US Food and Drug Administration; MCDBT, multi-cancer detection blood test; Me, methylation.
13+ cancers Genome-wide fragmentomics-related features
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
solution
302024692.html; 5. Gao Q, et al. J Clin Oncol. 2021;39(suppl 3):459.
Modeling Data Demonstrate That the Addition of MCED Testing to Routine Cancer Screening Could Result in:
• 3X as many cancers diagnosed as routine screening alone,1,a including identification of:
– An additional 11% 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 to 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.
aAssuming 100% uptake. Hackshaw A, et al. Br J Cancer. 2021;125(10):1432-1442. Current Screening (67M Screens) With Added
THE SCIENCE BEHIND MCED TESTS
Traditional Tissue vs Blood-Based Biopsy
Traditional Tissue Biopsy1,2 Blood-Based Biopsy3-5
• Usually invasive
• Only possible if tumor is visible and accessible
• Can be costly, risky, and potentially painful
• Only provides detailed information about cancer at the site and the time of biopsy
• Not as invasive as traditional biopsy
• Can characterize across all tumor stages
• Can produce real-time information for diagnosis, prognosis, and treatment
• May indicate potential treatment response
1. Sharma S, et al. Pathology. 2021;53(7):809-817; 2. Rodríguez J, et al. Oncol Ther. 2021;9(1):89-110; 3. Mathai RA, et al. J Clin Med. 2019;8(3):372; 4. Aarthy R, et al. Mol Diagn Ther. 2015;19(6):339-350; 5. Pinzani P, et al. Clin Chem Lab Med. 2021;59(7):1181-1200.
Cell-Free DNA (cfDNA)
The Basis for New Screening Modalities
Apoptosis
Necrosis
Secretion
Apoptotic bodies
Point mutations
Copy number alterations
Exosomal DNA
Rearrangements
Methylation changes
Protein biomarkers
cfDNA anomalies that can be measured and characterized in assays1,2
bp, basepairs; CH3, methyl group.
1. 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; 3. Lo Y, et al. Sci Transl Med. 2010;2(61):61ra91; 4. Mouliere F, et al. Sci Transl Med. 2018;10(466):eaat4921; 5. Fernández-Lázaro D, et al. Diagnostics (Basel). 2020;10(4):215.
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-DNA interactions
– Expression patterns (silencing, activation)
• Changes in DNA methylation patterns:
– Can contribute to tumorigenesis or progression
• ctDNA
– Can be identified and characterized via next-generation sequencing + machine learning
ctDNA, circulating tumor DNA.
Locke WJ, et al. Front Genet. 2019;10:1150.
Differentiating Available Cancer Screening From Cancer Risk Tests
• MCED testing is SCREENING for multiple cancers
• Genetic testing is RISK CALCULATION
Validation of the Assays Understanding Sensitivity and Specificity
Sensitivity
the test’s ability to detect a truepositive sample (eg, a patient with a particular cancer)
Specificity
the test’s ability to detect a true negative (eg, a patient who does not have that particular 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
Examples
97% Sensitivity would produce 3 false-negative results for every 100 samples from patients with cancer.
R. Front Public Health. 2017;5:307.
Negative Predictive Value (NPV)
percentage of all negative samples that are true negatives
97% Specificity would result in 3 false-positive signals for every 100 samples from patients with no cancer.
Trevethan
Criteria Important for a Cancer Screening Test Specificity and Sensitivity
Criteria1 Why Important
High specificity
To minimize false positives and thereby reduce unnecessary workup, overdiagnosis, overtreatment
High sensitivity To detect early tumors that may be curable by surgery
DETECT-A2,a
Asymptomatic/No cancer history
PATHFINDER3,b
Asymptomatic/No cancer history
SYMPLIFY4,c
Symptomatic
II5,d
JINLING6,e
Asymptomatic/No cancer history CanScan
All cancers except skin, CNS, leukemias
Lung, colon/rectum, liver, ovary, pancreas, and esophagus
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); cN=5461 symptomatic individuals aged ≥18 years referred for urgent investigation for a possible gynecologic, lung, or GI cancer or referred to a rapid diagnostic center with nonspecific symptoms that might be due to cancer; dN=639 (with cancer=351) + (noncancer=288); eN=3724 participants aged between 45 and 75 years without cancer-related symptoms; fSensitivity determined from the CCGA Substudy 3. CCGA, Circulating Cell-free Genome Atlas; CNS, central nervous system.
1. Duffy MJ, et al. Clin Chem Lab Med. 2021;59(8):1353-1361; 2. ; 3. Schrag D, et al. Lancet. 2023;402(10409):1251-1260; . Nicholson BD, et al. Lancet Oncol. 2023;24:733-743; 5. Gao Q, et al. J Clin Oncol. 2021;39(suppl 3):459; 6. Yang S, et al. Cancer Res. 2024;84(suppl 6):1263.
Criteria Important for a Cancer Screening Test
PPV and NPV
Criteria1 Why Important High PPV To reduce unnecessary workup, overdiagnosis, overtreatment
High NPV To reduce the probability of missing potentially curable tumors
Asymptomatic/No cancer history
Asymptomatic/No cancer history
cancer
N/A, not available.
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); cN=5461 symptomatic individuals aged ≥18 years referred for urgent investigation for a possible gynecologic, lung, or GI cancer or referred to a rapid diagnostic center with nonspecific symptoms that might be due to cancer; dN=639 (with cancer=351) + (noncancer=288); eN=3724 participants aged between 45 and 75 years without cancer-related symptoms.
1. Duffy MJ, et al. Clin Chem Lab Med. 2021;59(8):1353-1361; 2. ; 3. Schrag D, et al. Lancet. 2023;402(10409):1251-1260; . Nicholson BD, et al. Lancet Oncol. 2023;24:733-743; 5. Gao Q, et al. J Clin Oncol. 2021;39(suppl 3):459; 6. Yang S, et al. Cancer Res. 2024;84(suppl
Criteria Important for a Cancer Screening Cancer Signal of Origin (CSO) Identification
Criteria1 Why Important
Ability to localize site of tumor
To minimize imaging for localizing tumor site
DETECT-A2,a
Asymptomatic/No cancer history
PATHFINDER3,b
Asymptomatic/No cancer history Galleri
Thunder II5,d validation set With/Without cancer
JINLING6,e
Asymptomatic/No cancer history CanScan
Real-world experience7,f
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); cN=5461 symptomatic individuals aged ≥18 years referred for urgent investigation for a possible gynecologic, lung, or GI cancer or referred to a rapid diagnostic center with nonspecific symptoms that might be due to cancer; dN=639 (with cancer=351) + (noncancer=288); eN=3724 participants aged between 45 and 75 years without cancer-related symptoms; fN=53,744 MCED tests delivered; gSensitivity determined from the CCGA study.
1. Duffy MJ, et al. Clin Chem Lab Med. 2021;59(8):1353-1361; 2. Schrag D, et al. Lancet. 2023;402(10409):1251-1260; . Nicholson BD, et al. Lancet Oncol. 2023;24:733-743; 5. Gao Q, et al. J Clin Oncol. 2021;39(suppl 3):459; 6. Yang S, et al. Cancer Res. 2024;84(suppl 6):1263; 7. Westgate C, et al. J Clin Oncol. 2023;41(suppl 16):10519. Lennon AM, et al. Science. 2020;369(6499):eabb9601; 3. 4
Recent Findings Presented at Spring 2024 Oncology Research Conferences
• MCED test performance in cancer survivors (ASCO)1
– MCED test (Galleri) detected both cancer recurrences and new primaries in cancer survivors for whom multiple years had elapsed since their original diagnosis, potentially expanding surveillance options for this patient group
– Cancers that were not detected by MCED were predominantly early stage
– Test performance was similar in those with and without a cancer history
• Case report: DETECT-A participants with premalignant conditions (AACR)2
– When MCED testing (CancerSEEK) detected precancerous conditions in the DETECT-A study, surgical interventions prevented cancer development, and all patients were cancer-free at follow-up
• Performance of a multi-analyte, MCED blood test in a prospectively collected cohort (AACR)3
– Data from ASCEND2 trial (CancerGuard)
– Overall test sensitivity: 49.9%, specificity: 99.0%
– Sensitivity
• 54.8% for cancers without standard-of-care screening for average-risk populations
• 63.7% in the most-aggressive cancers with the shortest 5-year survival rate (pancreas, esophagus, liver, lung and bronchus, stomach, and ovary)
– Identified cancer stages across 21 solid and hematologic tumor organ sites that collectively represent >85% of incident cancers AACR, American Association for Cancer Research; ASCO, American Society of Clinical Oncology.
aCancerGuard is a refined version of the CancerSEEK test that includes analysis of methylated cfDNA and protein biomarkers.
1. Marinac C, et al. J Clin Oncol. 2024;42(suppl 16):1628; 2. Choudhry OA, et al. Canc Res. 2024;84(suppl 6):2449; 3. Gainullin V, et al. Canc Res. 2024;84 (suppl 7):LB100.
Meta-analyses of cfDNA-based
What We’ve Learned About cfDNA-Based MCEDs So Far
• Cancer at all stages can be identified by analyzing methylated cfDNA with machine learning
• Other notes:
– HPV-mediated misdiagnosis of CSO has been reported9
– False positives have resulted from clonal B-cell expansion10
aThe meta-analyses presented included 107 and 128 cfDNA-based MCED tests. FNR, false-negative rate; FPR, false-positive rate.
1. Lehman CD, et al. Radiology. 2017;283(1):49-58; 2. Nelson HD, et al. Ann Intern Med. 2016;64(4):226-235; 3. The National Lung Screening Trial (NLST) Research Team. N Engl J Med. 2011;365(5):395-409; 4. NLST Research Team. N Engl J Med. 2013;368(21):1980-1991; 5. Pinsky PF. Lung Cancer Manag. 2014;3(6):491-498; 6. Vahedpoor Z, et al. Taiwan J Obstet Gynecol. 2019;58(3):345-348; 7. Park JH, et al. Cancer Res. 2023;83(suppl 7):784; 8. Park JH, et al. J Clin Oncol. 2023;41(suppl 16):3069; 9. Myers DA, Wood B. Cancer Res. 2023;83(suppl 7):6503; 10. Xiang J, et al. Cancer Res. 2023;83(suppl 7):779.
CONSIDERATIONS FOR THE USE OF MCED SCREENING IN PRIMARY CARE PRACTICE
MCED Test Availability
• 1 MCED test is commercially available
• None are FDA approved
• There are no established guidelines beyond the MCED Consortium White Paper
• Patients can access the test on their own, thus providers should be aware of test and follow-up pathways
Suggested Eligibility Criteria for MCED Screening
• Who Is Eligible?
– Age ≥50 years
– Family or personal history of cancer
– History of childhood 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
– Exposure to cancer-causing substances (eg, fire smoke, tobacco smoke, radiation, sunlight)
– Chronic inflammation
– Immunosuppression
– Infectious agents (eg, viruses, parasites)
– Overweight/Obesity
– Tobacco
MCED testing should be used to complement recommended screening approaches to identify cancers they do not cover, NOT in place of current screening.
Multicancer Early Detection (MCED) Consortium. 2023. https://static1.squarespace.com/static/615c87aaea640d19cc98840b/t/6499fcaddf755715cc844f39/1687813293969/MCED+Consortium+Care+Delivery+Paper_Final.pdf; Putcha G, et al. JCO Precis Oncol. 2021;5:574-576.
Considerations When Discussing MCED With Patients
Potential Advantages
Increased and earlier cancer detection rate, including asymptomatic patients1,2
Trials demonstrate improving efficiency of testing, with increased PPV, decreased NNS1
Screening of organ sites currently without a screening modality2
Screening for multiple cancers at the same time1
Less-invasive procedures and potentially improved success of treatments2
May help reduce health disparities by increasing participation rates through improved access to screening2
Potential Disadvantages
Currently not covered by most insurance (commercial or government sponsored)1
“No Cancer Detected” does not rule out future cancer diagnosis; sensitivity limited Consequential cancers found sooner, but patient may not live any longer3
Possible harm from unnecessary diagnostic procedures due to false positives or missed diagnoses due to false negatives1,2
Overdiagnosis and overtreatment of cancers that would have otherwise never bothered the patient2,3
Inequities will increase if tests are not widely available, affordable, and acceptable to minority groups2
1. Klein EA, et al. Ann Oncol. 2021;32(9):1167-1177; 2. MCED Consortium. 2023. https://static1.squarespace.com/static/615c87aaea640d19cc98840b/t/6499fcaddf755715cc844f39/1687813293969/MCED+Consortium+Care+Delivery+Paper_Final.pdf; 3. Welch HG, Kramer B. STAT. 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 companies
– Out of pocket for currently available test is $949
– HSA/FSA-eligible
• Medicare Multi-Cancer Early Detection Screening Coverage (originally 2021, reintroduced March 2023 [House of Representatives] and June [Senate] 2023)1,2
– Not passed yet
– Supported by American Cancer Society, ASCO, Prevent Cancer Foundation, Association of Cancer Care Centers3
• 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 the lives of people with cancer and cancer survivors
• NCI Vanguard Study on Multi-Cancer Detection evaluating MCED assays for purpose of cancer screening5
Currently, there are no consensus guidelines that recommend population-level MCED screening.
FSA, flexible savings account; HSA, health savings account; NCI, National Cancer Institute. 1. Prevent Cancer Foundation. https://www.preventcancer.org/multi-cancer-early-detection/coverage-and-legislation/#coverage-act. Accessed May 17, 2024; 2. Congress.gov. https://www.congress.gov/bill/118th-congress/senate-bill/2085. Accessed May 17, 2024; 3. Sewell T. https://sewell.house.gov/2024/6/rep-sewell-s-legislation-to-expand-access-to-cuttingedge-cancer-screenings-passes-unanimously-in-the-house-ways-and-means-committee; 4. American Association for Cancer Research (AACR). Cancer Discov. 2022;12(4):876; 5. Minasian L, Castle PE. Accessed September 16, 2024. https://prevention.cancer.gov/sites/default/files/uploads/major_program/Cancer-Screening-Research-Network-MCED20220615.pdf.
REACH Initiative
(Real-world Evidence to Advance MCED 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
Successful Implementation of MCED Screening in a US-Based Health System A Case Study
team notified of eligible patients
screened for eligibility
called for pretest counseling within 2 business days MCED test ordered for interested patients
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
team
plan within
hours Patient notified and diagnostic tests scheduled Diagnostic results and next steps discussed with patient if confirmed positive
Patient notified and additional health screenings discussed as needed
• Initiation of treatment or first postdiagnosis specialist visit: 33 days
Follow-Up for a Positive Cancer Signal Test Result Should Be Individualized
• Based on:
– Data supporting the specific test, the invasiveness of additional diagnostic evaluations, the potential efficacy of available treatments
– Further workups may include laboratory tests, imaging (CT, MRI, PET, U/S, X-ray) bone scans, or tissue biopsy (see next slide)
CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; U/S, ultrasound. Nadauld LD, et al. Cancers (Basel). 2021;13(14):3501.
Suggested Clinical Care Pathways Following Common “Cancer Signal Detected” Results
Cancer Signal Origin Prediction
Multiple myeloma
Upper GI (esophagus, stomach)
Colorectal
Head and neck
Pancreas, gallbladder
Ovary
Lung
Liver, bile duct
Breast
Lymphoid neoplasm
Indeterminate
Proposed First-Line Procedures
Blood workup including peripheral blood smear, CBC with differential; chemistry tests including creatinine clearance, protein electrophoresis of blood/urine
Endoscopy
Colonoscopy
Physical exam, fiber optic exam, U/S
CT abdomen with IV contrast, MRCP, GI referral
Abdominal/Pelvic exam, U/S (preferred)
Blood work
CT chest with or without IV contrast
U/S, CT, GI referral
Diagnostic mammography with U/S (MRI if mammography screening within last 3 months)
CT (neck, chest, abdomen, pelvis) with IV contrast, PET-CT
CT (neck, chest, abdomen, pelvis) with IV contrast, PET-CT
CBC, complete blood count; IV, intravenous; MRCP, magnetic resonance cholangiopancreatography.
Adapted from Nadauld LD, et al. Cancers (Basel). 2021;13(14):3501.
Conclusions
• Blood-based MCED tests can successfully use methylated cfDNA to detect a cancer signal and its point of origin
• Modeling studies demonstrate that adding MCED testing to routine asymptomatic cancer screening protocols could result in
– 3X as many cancers diagnosed than with routine screening alone
– 17% fewer cancer deaths per year
• Significant barriers to incorporation of MCED screening into everyday practice include lack of guidelines, organizational recommendations, and insurance coverage
• MCED tests are intended to complement other screening strategies, not to be used instead of current cancer screening methods
REMINDER A Resource for Clinicians
