FightCRC

Published March 31, 2026

A Patient Guide to Cancer Screening Blood Tests

Blood tests are becoming a bigger part of the cancer screening conversation. That can be helpful, but it can also be confusing.

If you have heard about Shield, Freenome, Galleri, Cancerguard, or other blood tests, you are not alone. Many patients are trying to sort out what these tests do, who they are for, and whether they replace colonoscopy or stool-based screening.

We want to break it down in plain language for you.

What patients need to know about colorectal cancer blood tests and multi cancer blood tests:

Blood tests for cancer screening are getting a lot of attention. You may be seeing ads, news stories, or social posts that make it sound like one blood test can answer every question about cancer screening.

That is where things can get confusing.

A blood draw may feel simpler and easier to fit into daily life than a colonoscopy or stool test. But not all cancer blood tests are designed to do the same job.

Some blood tests are designed to look for colorectal cancer specifically. Others are designed to look for signals from many cancers at once. These are often called multi cancer early detection tests, or MCED tests.

At Fight CRC, we want patients to have clear, practical information that helps them ask better questions and make informed decisions.

Test	Company	Type	Main purpose	Current status	Key patient takeaway
Shield	Guardant Health	Single cancer blood test	Colorectal cancer screening	FDA approved for average risk adults 45 and older	Designed for colorectal cancer screening, but positive results still need colonoscopy
Freenome CRC test	Freenome, licensed to Exact Sciences in the U.S	Single cancer blood test	Colorectal cancer screening	Investigational	Important emerging option, but not the same as an approved screening choice today
Galleri	GRAIL	MCED blood test	Looks for signals from many cancers	Commercially available, not FDA approved	Not a colorectal cancer screening test and does not replace standard screening
Cancerguard	Exact Sciences	MCED blood test	Looks for signals from many cancers	Commercially available as an LDT, not FDA approved	Not a colorectal cancer screening test and does not replace standard screening
Shield MCD	Guardant Health	MCED platform under study	Looks for signals from many cancers	Research setting	Different from Shield CRC screening and easy for patients to confuse
Avante ct MCD	ClearNote Health	MCED platform under study	Looks for signals from many cancers	Research setting	Another emerging platform being studied in national trials

What is the difference between a colorectal cancer blood test and an MCED test?

Question	Colorectal cancer blood test	MCED blood test
What is it designed to find?	Colorectal cancer	Signals linked to many cancers
Is it a colorectal cancer screening test?	Yes, if it is specifically designed and approved or validated for that purpose	No
Does it detect polyps or precancers?	Sometimes, but current blood based CRC tests are much less effective at finding advanced precancerous lesions than cancer itself	No. MCED tests are not designed to find colorectal polyps or precancers
Can it diagnose cancer?	No	No
What happens after a positive test?	Colonoscopy is usually the next step	Additional workup, often imaging and sometimes procedures

What do sensitivity and specificity mean?

These terms can sound technical, but the ideas are simple.

Term	Plain language meaning	Why it matters
Sensitivity	How often the test finds cancer when cancer is really there	Higher sensitivity means fewer cancers are missed
Specificity	How often the test is negative when cancer is not there	Higher specificity means fewer false alarms
False positive	The test says something may be wrong when no cancer is found	Can lead to stress, imaging, procedures, and extra cost
False negative	The test misses a cancer that is actually present	Can create false reassurance

In everyday terms:

Higher sensitivity means the test is better at finding cancer when it is there.

Higher specificity means the test is better at avoiding false alarms.

False positives can lead to more testing, more worry, and more cost.

False negatives can create false reassurance and delay follow up.

Why Precancer Matters in Colorectal Cancer Screening

This is one of the most important things to understand.

Colorectal cancer screening is not only about finding cancer early. It is also about finding advanced precancerous lesions before they turn into cancer.

That is why a test should not be judged only by whether it can find cancer that is already there. In colorectal cancer, the ability to catch precancer matters too.

What Patients Should Know About MCED Tests

MCED tests are designed to look for signals from many cancers, not specifically to screen for colorectal cancer.

Patients may hear about tests such as Galleri and Cancerguard. They may also hear about MCED platforms under study such as Shield MCD and Avantect MCD. The National Cancer Institute (NCI) selected Shield MCD and Avantect MCD for its Vanguard Study, which shows how quickly this area is evolving. (NCI Vanguard Study)

The most important takeaway for patients is this: MCED tests do not replace recommended colorectal cancer screening. The American Cancer Society says blood-based tests are not currently included in the ACS colorectal screening guideline, and the USPSTF says its colorectal cancer screening recommendation does not include serum tests because of limited available evidence. (American Cancer Society screening tests page, USPSTF recommendation)

A simple way to think about MCED tests:

They may sound broader, but broader does not mean they replace standard screening.

They are not colorectal cancer screening tests.

A positive result can lead to additional workup, including imaging or other follow up testing.

Common questions about blood tests for cancer screening

If you are asking…	The most helpful answer is…
I want screening specifically for colorectal cancer	Choose a colorectal screening option with your doctor based on your risk level, symptoms, and which test you are most likely to complete
I want a blood test instead of a stool test or colonoscopy	Ask whether you are average risk and whether a blood based CRC screening option is appropriate
I want one blood test to replace all screening	No blood test does that today
I want a test that looks for many cancers	Understand that MCED tests are different from colorectal screening tests and do not replace standard screening

Questions patients should ask before choosing a blood test

These questions can help start the conversation with your doctor:

Am I average risk or high risk for colorectal cancer?

Is this test meant for colorectal cancer specifically or for many cancers?

Is this test FDA approved, investigational, or offered as a laboratory developed test?

How well does it detect colorectal cancer?

How well does it detect advanced precancerous lesions?

What happens if my result is positive?

What happens if my result is negative but I have symptoms?

Will my insurance cover the test and any follow up testing?

Would a stool based test or colonoscopy be a better fit for me?

Bottom line

Blood tests are becoming a bigger part of the cancer screening conversation, but patients still need clear information.

A colorectal cancer blood test is not the same as a multi cancer blood test.

Some blood tests are designed for colorectal cancer screening. Others are designed to look for many cancers at once. They have different goals, different evidence, and different follow up steps.

What matters most is understanding:

what the test is actually designed to find

whether it fits your risk level

what the next step will be if the result is positive

whether a different screening option may be a better fit for you

The best screening choice is the one that fits your risk, your questions, and the next steps you are willing and able to take.

And whatever option you choose, do not ignore symptoms and do not assume one blood test can replace every recommended screening test.

For readers who want to review the guidance directly, start with the American Cancer Society colorectal cancer screening guideline, the American Cancer Society screening tests page, and the USPSTF colorectal cancer screening recommendation. (ACS guideline, ACS screening tests page, USPSTF recommendation)

Blood Test FAQ:

Can a blood test replace a colonoscopy?

No. A blood test cannot replace colonoscopy in every situation. If a colorectal cancer blood test is positive, colonoscopy is usually the next step. The FDA also states that Shield is not a replacement for diagnostic or surveillance colonoscopy. (FDA Shield approval)

Are multi cancer blood tests the same as colon cancer blood tests?

No. MCED tests and colorectal cancer blood tests are built for different purposes.

MCED tests look for possible signals from many cancers.

Colorectal cancer blood tests are designed specifically around colorectal screening.

(NCI Vanguard Study)

Is a negative blood test enough to rule out colorectal cancer?

No. A negative test does not rule out cancer and should not override symptoms or medical advice. The FDA says a negative Shield result does not guarantee that a person does not have colorectal cancer. (FDA Shield approval)

Does insurance cover a colorectal cancer blood test or an MCED test?

Sometimes, but coverage is uneven and depends on the test and your insurance.

Medicare covers blood-based biomarker screening tests for colorectal cancer every 3 years for eligible adults ages 45 to 85 who are at average risk and have no symptoms. Medicare says you pay nothing if your provider accepts assignment. (Medicare blood based biomarker screening coverage)

Medicare also says that if you have a positive result from a Medicare covered blood based colorectal screening test, it covers a follow up colonoscopy as a screening test. (Medicare colonoscopy coverage)

Private insurance coverage for colorectal cancer blood tests is still evolving and can vary by plan, network, and whether the test is included in that plan’s preventive benefits.

MCED tests are often not covered by insurance. Galleri says most health insurance plans do not cover the test, and Cancerguard says it is not currently covered by health insurance. (Galleri cost and coverage, Cancerguard request page)

If I pay out of pocket for the blood test, will that cause problems getting follow up testing covered?

It can, depending on your insurance and what follow up care is needed.

With Medicare, the clearest coverage language applies when the original blood based colorectal screening test itself is Medicare covered. Medicare says a positive result from a Medicare covered blood based biomarker screening test can be followed by a covered screening colonoscopy. (Medicare colonoscopy coverage, Medicare blood based biomarker screening coverage)

With private insurance, patients should not assume that paying cash for the original test automatically guarantees coverage of all follow up imaging, procedures, or colonoscopy. Plans may treat follow up care differently depending on whether the first test was covered, whether the next step is considered screening or diagnostic, and whether the provider and facility are in network.

For MCED tests, follow-up may include imaging or other diagnostic workup, and Galleri states that the cost of the test does not include that diagnostic testing. (Galleri for HCPs)

A practical way to protect yourself is to ask these questions before testing:

Is this test covered by my plan?

If the result is positive, is the next step considered screening or diagnostic?

Will the follow up colonoscopy, imaging, lab work, or specialist visits be covered?

Do I need to use a specific in network lab, doctor, or facility?

Reference Links:

American Cancer Society colorectal cancer screening guideline: https://www.cancer.org/cancer/types/colon-rectal-cancer/detection-diagnosis-staging/acs-recommendations.html

American Cancer Society colorectal cancer screening tests page: https://www.cancer.org/cancer/types/colon-rectal-cancer/detection-diagnosis-staging/screening-tests-used.html

USPSTF colorectal cancer screening recommendation: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/colorectal-cancer-screening

FDA Shield approval information: https://www.fda.gov/medical-devices/recently-approved-devices/shield-p230009

Published March 26, 2026

Br J Cancer. 2026 Mar 25. doi: 10.1038/s41416-026-03373-6. Online ahead of print.

ABSTRACT

BACKGROUND: Given the global issue of the rising incidence of early-onset colorectal cancer (CRC), we tested the hypothesis that tumor vasculature phenotypes might vary with age at CRC diagnosis.

METHOD: We used in situ multispectral immunofluorescence combined with digital image analysis and machine learning to measure expression of endothelial cell markers [ACKR1 (DARC), CD34, CD36, KDR (VEGFR2), LAMB1 (laminin β1), MADCAM1] and KRT (keratin) in 843 tumors derived from 4476 CRC cases in U.S.-wide prospective cohorts under the prospective cohort incident-tumor biobank method.

RESULTS: Overall CD34⁺ vessel and CD34⁺LAMB1⁺ vessel densities inversely correlated with younger age at CRC diagnosis (both P_trend < 0.0001). In the inverse probability-weighted multivariable-adjusted logistic regression analyses, compared to age ≥70, odds ratios (with 95% confidence interval) for high (vs. low) overall vessel density were 0.85 (0.74-0.99) for age 55-69 and 0.63 (0.48-0.81) for age <55, and those for high (vs. low/negative) CD34⁺LAMB1⁺ vessel density were 0.56 (0.47-0.65) for age 55-69 and 0.28 (0.20-0.40) for age <55.

CONCLUSIONS: Hypovascularities of overall and CD34⁺LAMB1⁺ vessels may be microenvironmental characteristics of early-onset CRC if validated by independent studies. Our findings highlight age-related tumor pathobiological differences. Identifying specific biomarkers of early-onset CRC can provide pathogenetic and etiological clues.

PMID:41882312 | DOI:10.1038/s41416-026-03373-6

Published March 19, 2026

Cancer Sci. 2026 Mar 18. doi: 10.1111/cas.70363. Online ahead of print.

ABSTRACT

The incidence of early-onset cancers, commonly defined as cancers diagnosed before age 50 years, has been increasing globally over recent decades. In particular, the incidence of several early-onset digestive system cancers, including cancers of the esophagus, stomach, colorectum, liver, extrahepatic bile duct, gallbladder, and pancreas, has been reported to be increasing in multiple regions. To elucidate carcinogenic mechanisms and develop effective prevention, earlier detection, and treatment strategies, further evidence is needed on risk factors and clinical, pathological, and molecular characteristics. In this review, we summarize the current evidence on these characteristics, highlight shared and distinct features across organ sites, and discuss research opportunities to address the rising burden of early-onset digestive system cancers.

PMID:41850249 | DOI:10.1111/cas.70363

Published March 19, 2026

J Natl Cancer Inst. 2026 Mar 19:djag047. doi: 10.1093/jnci/djag047. Online ahead of print.

ABSTRACT

Understanding long-term trends in cancer mortality in rural and urban areas can provide additional insight into factors contributing to rural-urban disparities in cancer mortality and inform public policies. We examined trends in age-standardized cancer mortality rates (overall, lung, colorectal, female breast, and prostate cancers) by urbanicity of county of residence using National Center for Health Statistics data. During 1969-2023, the highest all-cancer mortality rates shifted from large metropolitan areas to nonmetropolitan areas with the smallest urban population. The crossover occurred in the 1990s in males and early 2000s in females, with the rural-urban mortality gap widening in subsequent years. A similar pattern was observed for lung, colorectal, and breast cancer mortality. The shift in the high cancer burden from urban to rural areas likely reflects geographic redistribution of social determinants of health, which underpins the cancer continuum from exposure to risk factors and prevention to access to high-quality diagnosis and treatment.

PMID:41850332 | DOI:10.1093/jnci/djag047

Published March 14, 2026

Clin Gastroenterol Hepatol. 2026 Feb 17:S1542-3565(26)00066-2. doi: 10.1016/j.cgh.2026.01.037. Online ahead of print.

ABSTRACT

The ability to precisely determine future risk of advanced neoplasia (AN; high-grade dysplasia and/or colorectal cancer [CRC]) in patients with ulcerative colitis (UC) and low-grade dysplasia (LGD) is a major unmet need. Given the uncertainty in existing prognostic data, current guidelines advise incorporating expert opinion into management decisions, which can be challenging and imprecise.¹ In addition to supporting clinician decision-making, having quantitative estimates of cancer risk also increases patients’ ability to make informed shared decisions on surgery vs continued intensive surveillance following a LGD diagnosis.².

PMID:41713829 | DOI:10.1016/j.cgh.2026.01.037

Published March 12, 2026

Lancet Oncol. 2026 Mar;27(3):e141-e149. doi: 10.1016/S1470-2045(25)00714-4.

ABSTRACT

Currently, no consensus exists regarding the definition of oligometastatic pancreatic ductal adenocarcinoma, its necessary diagnostic measures, and potential treatment approaches. To address these knowledge gaps, the OligoPanc project brought together an interdisciplinary group of experts to establish consensus using a modified Delphi process and clinical vignettes. Participants agreed that the number of metastatic lesions and the number of affected organs are key elements in defining oligometastatic pancreatic ductal adenocarcinoma. Specifically, up to three lesions in a single organ, either the liver or the lung, define oligometastatic pancreatic ductal adenocarcinoma and could be either synchronous or metachronous. Necessary diagnostics include a triple-phase contrast-enhanced CT scan of the chest and abdomen and MRI of the liver with a hepatocyte-specific contrast agent. In unclear cases, [¹⁸F]fluorodeoxyglucose-PET CT or MRI can be considered. A multidisciplinary tumour board is essential. Patient-intrinsic factors, including age, do not define oligometastatic disease but should be considered for any treatment decision. Systemic treatment before any local consolidative treatment, including surgery, stereotactic ablative radiotherapy, or other locally ablative techniques, is mandatory. The proposed definition should be incorporated into future trials to improve comparability and enable validation.

PMID:41785904 | DOI:10.1016/S1470-2045(25)00714-4

Published March 12, 2026

CA Cancer J Clin. 2026 Mar-Apr;76(2):e70067. doi: 10.3322/caac.70067.

ABSTRACT

Colorectal cancer (CRC) is the second most common cancer-related death in the United States and ranks first in adults younger than 50 years. Every 3 years, the American Cancer Society reports on CRC occurrence based on incidence from population-based cancer registries and mortality from the National Center for Health Statistics. Overall, CRC incidence declined by 0.9% annually during 2013-2022 driven by decreases of 2.5% annually in adults aged 65 years and older. In sharp contrast, incidence rates increased by 3% annually in adults aged 20-49 years and by 0.4% annually in adults aged 50-64 years dominated by tumors in the distal colon and rectum. Consequently, overall rectal cancer incidence increased by 1% annually from 2018 to 2022 after decades of decline and now accounts for 32% of all CRC, up from 27% in the mid-2000s. Increasing CRC incidence in adults aged 50-64 years was confined to regional and distant-stage diagnosis (1.1%-1.3% annually during 2013-2022), likely contributing to an upturn in mortality in this age group of 1% annually since 2019 that was steepest (2.3% annually) in White individuals. Mortality has increased in adults younger than 50 years by 1% annually since 2004, whereas rates have decreased in adults 65 years and older by 2.3% annually since 2012. Despite steady progress for older adults, both CRC incidence and mortality are increasing in adults younger than 65 years who are in the prime of life, underscoring an urgent need for etiologic research to discover the cause of the rising trend. Meanwhile, morbidity and mortality could be mitigated with earlier diagnosis, through screening and educating clinicians and the general public about CRC symptoms, and greater attention to the unique needs of younger patients, including discussion about the preservation of fertility and sexual health.

PMID:41769777 | PMC:PMC12951547 | DOI:10.3322/caac.70067

Published March 12, 2026

Adv Radiat Oncol. 2025 Nov 9;11(2):101952. doi: 10.1016/j.adro.2025.101952. eCollection 2026 Feb.

ABSTRACT

PURPOSE: Although salvage surgery is the standard of care for locoregionally recurrent anal cancer, few local options exist for inoperable pelvic recurrences. Newly diagnosed anal cancer arising in a previously irradiated field also provides a unique treatment challenge, as delivery of standard doses would result in unsafe cumulative dose to pelvic structures. We aimed to evaluate efficacy and toxicity of a hyperfractionated accelerated reirradiation (reRT) regimen for such patients.

METHODS AND MATERIALS: Patients treated with hyperfractionated accelerated reRT at a single institution between 2005 and 2024 for nonmetastatic inoperable locoregionally recurrent anal cancer or primary anal cancer in a previously irradiated field were included. The reRT regimen consisted of 1.5 Gy in twice daily fractions separated by 6 hours to a median (range) of 39 (30-51) Gy. Complete clinical response rates, recurrence rates, and toxicities were reported.

RESULTS: The median (IQR) follow-up was 13.4 (7.5-42.2) months. Twenty-six (74.3%) patients were treated with reRT for recurrent anal cancer, and 9 (25.7%) patients were treated with reRT for a new squamous cell carcinoma of the anus (SCCA) primary after prior pelvic radiation. The complete clinical response rate was 46.2% among patients with recurrent anal cancer and 77.8% among patients with a new SCCA primary after prior pelvic radiation. Two-year locoregional recurrence rate was 64.0% among patients with recurrent anal cancer and 22.0% among patients treated with reRT for a new SCCA primary after prior pelvic radiation. Eight patients (22.9%) developed acute grade 3 toxicity and 10 (28.6%) developed late grade 3-4 toxicity.

CONCLUSIONS: Hyperfractionated accelerated reRT results in promising complete clinical response rates that appear to translate into durable pelvic control for patients with recurrent anal cancer or a new SCCA primary after prior pelvic radiation. Acute toxicity appears similar to initial standard chemoradiation, but limiting reRT doses to 39 Gy may reduce the risk of serious late toxicity.

PMID:41726003 | PMC:PMC12918202 | DOI:10.1016/j.adro.2025.101952

Published March 12, 2026

Sci Rep. 2026 Feb 13. doi: 10.1038/s41598-026-39644-8. Online ahead of print.

ABSTRACT

Somatic mutations in KRAS are a common driver of colorectal cancer (CRC) and present at different frequencies by race, sex, tumor site, ethnicity, and genetic similarity. Inherited germline variants may influence tumor somatic mutation frequency by altering mutation or DNA repair processes or altering cellular, immunological and/or microenvironmental responses after a mutation. We hypothesized that the germline genetic background modifies somatic KRAS mutation frequency in CRC. To test this, we performed a genome-wide association study (GWAS) in 7071 individuals with CRC, using KRAS mutation status as the phenotype. Single-nucleotide variants were chosen for validation analyses based on P values from the discovery GWAS, predicted in silico functional effects, and proximity to genes with potential cancer relevance. A validation analysis of 101 SNVs of interest was performed in 2482 individuals. No SNVs were significantly associated with KRAS-mutant CRC (P value < 0.0005). One variant rs73067863-T showed a non-significant exploratory association with fewer KRAS-mutant tumors in the combined sample (P value = 9.7 × 10^-7, OR = 0.75). Follow-up studies are needed to determine if these or other germline variants impact population differences in KRAS mutations in CRC.

PMID:41688657 | DOI:10.1038/s41598-026-39644-8

Published March 12, 2026

BMC Med. 2026 Feb 5;24(1):146. doi: 10.1186/s12916-026-04675-5.

ABSTRACT

BACKGROUND: Physical activity is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene-physical activity interaction analysis.

METHODS: Using logistic regression (1-d.f), two-step screening and testing method (EDGE), and joint tests (3-d.f), we analyzed interactions between common genetic variants across the genome and physical activity in relation to CRC risk. Self-reported physical activity levels were categorized as active (≥ 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk; 39,992 participants) and as study- and sex-specific quartiles of activity (42,602 participants).

RESULTS: Physical activity was inversely associated with CRC risk overall (OR [active vs. inactive] = 0.85; 95% CI = 0.81-0.90). The two-step EDGE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and physical activity for CRC risk (p-interaction = 2.6 × 10^-8). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95% CI = 0.75-0.85), but no significant physical activity-CRC associations among CT or TT carriers. When physical activity was modeled as quartiles, the 1-d.f. test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between physical activity and CRC (p-interaction = 3.5 × 10^-8). Stratification at this locus showed that an increase in physical activity (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95% CI = 0.72-0.82).

CONCLUSIONS: In summary, we identified two genetic variants that modified the association between physical activity and CRC risk. One of them, related to GREM1 and SCG5, suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be involved in the protective association between physical activity and colorectal carcinogenesis.

PMID:41645200 | PMC:PMC12973902 | DOI:10.1186/s12916-026-04675-5