Gastroenterology. 2026 Apr 1:S0016-5085(26)00303-3. doi: 10.1053/j.gastro.2026.02.047. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Colorectal cancer screening reduces mortality, yet uptake remains suboptimal. Various interventions aim to improve screening rates, but their comparative effectiveness is unclear. We aim to evaluate the effectiveness of colorectal cancer screening uptake interventions using a systematic review and network meta-analysis.

METHODS: We analyzed data from 76 randomized clinical trials across eight intervention strategies: patient navigation, mailed FIT outreach, educational multimedia, reminder-only, choice-based outreach, colonoscopy outreach, multistep, and usual care. Network meta-analysis compared interventions using risk ratios (RRs) and 95% confidence intervals (CIs). P-scores and rankograms assessed intervention rankings. Risk of bias was assessed, and certainty of evidence was graded using the GRADE framework.

RESULTS: Patient navigation (RR 1.58, 95% CI 1.23-2.02; P-score 0.81) and mailed FIT outreach (RR 1.36, 95% CI 1.07-1.74; P-score 0.79) were the most effective strategies, significantly outperforming usual care. Educational multimedia (RR 1.27, 95% CI 0.91-1.78) and reminder-only interventions (RR 1.24, 95% CI 0.98-1.57) showed modest effects. Choice-based outreach and colonoscopy outreach were not significantly more effective than usual care. Mailed FIT outreach was superior to colonoscopy outreach (RR 1.35, 95% CI 1.11-1.63), and patient navigation outperformed reminder-only interventions (RR 1.48, 95% CI 1.14-1.94). In low baseline uptake settings (<30%), mailed FIT outreach was most effective (RR 3.12, 95% CI 1.70-5.71), while educational multimedia performed best in higher uptake populations (≥30%) and in recent studies (2021-2024). Majority of studies were at low risk of bias while the certainty of evidence mostly ranged from moderate to low.

CONCLUSION: Patient navigation and mailed FIT outreach are the most effective strategies for increasing colorectal cancer screening uptake, particularly in low baseline uptake populations. Educational multimedia shows promise in recent years and high baseline uptake settings, offering a scalable alternative.

PMID:41932450 | DOI:10.1053/j.gastro.2026.02.047

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Gastroenterology. 2026 Mar 30:S0016-5085(26)00265-9. doi: 10.1053/j.gastro.2026.02.044. Online ahead of print.

NO ABSTRACT

PMID:41921823 | DOI:10.1053/j.gastro.2026.02.044

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Advocacy doesn’t start in a policy meeting. It starts with people—ordinary individuals who experience something extraordinary and choose to act.

Each month, we’re shining a light on advocates across the Fight CRC community who are turning personal experiences into meaningful change. These are the voices pushing for better research, stronger policies, and more support for every person affected by colorectal cancer.

This month, we’re honored to feature Alex Glade. Grounded in love for her family and a deep sense of purpose, Alex is transforming loss into action—working to ensure others have more time, more connection, and more hope.

Read more about Alex’s advocacy journey below.

What first got you involved in advocacy and the fight against colorectal cancer?

We took my mom to urgent care in late January 2023, drove her to the Emergency Department the same day, and she was diagnosed with Stage IV colon cancer. She was in and out of the emergency department and in pain until she passed away less than 80 days later. It was heartbreaking to witness her decline. She meant the world to our family and helped me raise my three kids.

I would say that the pain of losing her was so hard to articulate, and my grief had nowhere to go. I think I reached out to several people, and Brooks Bell shared that FightCRC was doing incredible work and collaboration to support CRC Fighters, survivors, and family members advancing research, policy, and actions to truly make the patient and caregiver experience healthier, more informed, and more supported.

I think I even missed the signup deadline to do Call-on Congress in 2024, but when I reached out, Olivia Henswel was kind enough to welcome me. Everyone at Call-on Congress was so genuinely caring. They truly welcome and empower any community member to find what they want to affect related to the fight.

FightCRC is one of those organizations that has no ego, it’s all about supporting people and making a positive impact. Of all the organizations I’ve worked for or volunteered with, it has been remarkable to see how much FightCRC cares about the mission and all people who are not only affected by CRC but also raising awareness about it (hopefully allowing more people to live fully).

What encouraged you to take your advocacy beyond Call-on Congress?

A few days before my mom passed, I had asked her if she had any wishes or hopes. She said she hoped that nobody would have to experience colorectal cancer. It thrust me into a total reexamination of how I invest the rest of my time on earth and what really matters.

Since then, I have wanted to double down on a few things, being in service to others and to care deeply and enact love for family, friends, and strangers. I’ve tried to better understand how we (as people) learn about our own health and what decisions we can make and when so that people can thrive and live healthier, connected, and purpose-filled lives.

I hoped to make mom’s life story mean something to people outside our family and use it to drive helpful action in the world. She lived a life of service to others and always cared about helping family, friends, and her community. She began her adult life as a teacher, and in a way, sharing her story can continue to educate and motivate others to care for their health in a preventive way while supporting those who are currently impacted by CRC.

It can shift a story of loss and allow my mom’s incredibly loving and caring spirit to continue helping others. I hope that our work could potentially give others more time with their families. My mom fought hard because she loved her family, and time with us was something she cherished. I would hope I could help others indirectly or directly have many more healthy years in which they thrive and ask how they can use their lives to support others.

The post Advocate Highlight appeared first on FightCRC.

Cancer Epidemiol Biomarkers Prev. 2026 Apr 1. doi: 10.1158/1055-9965.EPI-25-1754. Online ahead of print.

ABSTRACT

BACKGROUND: Red and/or processed meat are established colorectal cancer (CRC) risk factors. Genome-wide association studies (GWAS) have reported over 200 variants associated with CRC risk. We used functional annotation data to identify subsets of variants within known pathways to construct pathway-based Polygenic Risk Scores (pPRS) to assess interactions with meat intake.

METHODS: A pooled sample of 30,812 cases and 40,504 CRC controls from 27 studies were analyzed. Quantiles for red and processed meat intake were constructed. 204 GWAS variants were annotated to genes with AnnoQ and assessed for overrepresentation in PANTHER-reported pathways. pPRS’s were constructed from significantly overrepresented pathways. Covariate-adjusted logistic regression models evaluated interactions between pPRS and red or processed meat intake in relation to CRC risk.

RESULTS: A total of 30 variants were overrepresented in four pathways: Presenilin-Alzheimer disease, Cadherin/WNT-signaling, Gonadotropin-releasing hormone receptor, and TGF-β signaling. We found a significant interaction between TGF-β-pPRS and red meat intake (ORint = 0.95; 95% CI = 0.92-0.98; p = 0.003). When variants in the TGF-β pathway were assessed, we observed significant interactions of red meat with rs2337113 (intron SMAD7 gene, Chr18), and rs2208603 (intergenic region BMP5, Chr6) (p = 0.0005 & 0.036, respectively). There was no evidence of pPRS x red meat interactions for other pathways or with processed meat Conclusions:This pathway-based interaction analysis revealed a statistically significant interaction between variants in the TGF-β pathway and red meat consumption that impacts CRC risk.

IMPACT: These findings shed light into the possible mechanistic link between red meat consumption and CRC risk.

PMID:41920173 | DOI:10.1158/1055-9965.EPI-25-1754

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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. 

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

What do sensitivity and specificity mean? 

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

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 

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 

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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

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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

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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

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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

The post Automated Phenotyping With Artificial Intelligence Predicts Future Advanced Neoplasia Risk in Colitis-associated Low-grade Dysplasia appeared first on FightCRC.

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

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