Cancer screening and early detection remain critical tools in reducing cancer-related illness and death—yet many cancers still lack effective screening tests. According to Jose Delgado, MD, a board-certified internal medicine physician practicing in Boulder, Colorado, advances in prevention, early detection, and emerging blood-based cancer screening technologies offer promise, but also require careful consideration. In this article, Dr. Delgado reviews current cancer screening guidelines, the importance of lifestyle-based prevention, and what patients should know about newer multicancer detection tests.
by Jose Delgado, MD
Internal Medicine at Boulder Medical Center
Despite overall declining mortality rates from cancer due to reduced exposures (i.e., tobacco smoking), cancer screening, and more effective treatments, cancer remains the second most common cause of death in the U.S. and Europe behind cardiovascular diseases.
However, certain cancers continue to have very poor survival rates because of their aggressive nature, late-stage diagnosis due to the lack of available screening tests, and/or resistance to treatment. These include cancers of the brain, liver, esophagus, stomach, and pancreas. [1]
For other cancers, such as uterine cancer and breast cancer in certain age groups, mortality rates have remained unchanged. In contrast, mortality rates for throat and anal cancers are increasing, in part due to infection with the human papillomavirus (HPV). [2]
Current Cancer Screening Recommendations
Currently, screening tests are recommended for only four cancer types: colorectal, cervical, breast, and lung (for individuals with a sufficient smoking history). This is because research has proven that screening for these specific cancers demonstrates a well-established net benefit.
Prostate cancer screening with the PSA blood test is more complicated, as available data have not shown a clear mortality benefit that outweighs the risks of complications from diagnostic procedures and treatments. [3]
However, over the last five years, our ability to diagnose and treat prostate cancer has improved significantly through prostate MRIs, advanced tests such as the 4Kscore, SelectMDx, ExoDx, and active surveillance strategies. With updated research, prostate cancer screening may eventually become officially recommended.
Skin cancer screening should not be overlooked and is beneficial, particularly for individuals at higher risk for melanoma or certain skin types. Frustratingly, up to 70% of cancer deaths are from cancers for which no screening test currently exists. [4]
Why Early Detection Matters
Despite major advances in the treatment of certain cancers, early detection, before symptoms develop, remains the most effective way to combat this disease.
Primary Prevention: Reducing Cancer Risk Before It Starts
To state the obvious, prevention remains the foundation of cancer care. As Benjamin Franklin famously said, “An ounce of prevention is worth a pound of cure.”
An estimated 90–95% of cancers are related to modifiable lifestyle and environmental factors rather than genetics. These include smoking, poor diet (processed food, red meat, diets low in fruits and vegetables), obesity, physical inactivity, excess alcohol consumption, sun exposure (UV radiation), infections (HPV, HIV, viral hepatitis), and environmental pollutants.
The importance of focusing on a healthy lifestyle and living in a safe environment with access to clean air, water, and healthy food choices cannot be overstated.
Preventive strategies also include the Pap test for cervical cancer screening and colonoscopy for colorectal cancer screening, both of which offer the potential to diagnose and treat precancerous lesions before they progress to cancer. The HPV vaccine (Gardasil 9) represents the first vaccine capable of preventing many HPV-related cancers.
Advances in Multicancer Detection (MCD) Tests
Over the last few years, advances in genomics and machine learning have led to the development of multicancer detection (MCD) tests. Although none are yet FDA-approved, this field is growing rapidly, with numerous large-scale research trials underway.
An MCD test is basically a blood test, or so-called liquid biopsy, that detects various biological signals released by abnormal or cancerous cells. These signals include cancer-specific DNA mutations, methylation patterns, small-molecule metabolites, and other tumor-derived biomarkers. There are currently six MCD tests commercially available in the U.S. and another five available outside the U.S. (5).
These are offered as Laboratory Developed Tests (LDTs) that do not require FDA approval, provided a CLIA-certified Lab performs them. The two I will focus on are at the forefront, with the best research and ongoing large clinical trials: Galleri (GRAIL) and Cancerguard (Exact Sciences).
Galleri Multicancer Detection Test
The Galleri MCD test detects cancer-specific DNA methylation patterns in cell-free DNA shed by tumors into the bloodstream. It can detect more than 50 cancer types and uses machine learning to predict the tissue of origin, known as the cancer signal origin (CSO).
Preliminary results from the ongoing PATHFINDER-2 trial demonstrate a positive predictive value (PPV) of 61.6%, an improvement over earlier trials that showed PPVs in the 30–40% range.[6]
The test has very high specificity and negative predictive value (over 99%), meaning a negative result is highly reassuring. Additional PATHFINDER-2 findings included a sevenfold increase in cancer detection beyond standard screening, accurate tumor-site identification in 92% of cases, and early-stage detection (stage I or II) in more than half of diagnosed cancers.
Cancerguard Multicancer Detection Test
The Cancerguard MCD test, developed by the makers of the stool-based Cologuard test, detects cell-free DNA and various proteins in the blood (specifically eight biomarkers and 16 cancer gene mutations) for more than 50 cancer types.
Unlike Galleri, Cancerguard does not identify the site of origin, so follow-up imaging, such as PET-CT, is required when results are positive. Results from the DETECT-A trial demonstrate an overall PPV of 28% and a negative predictive value of 99.3%. [7]
Do Multicancer Detection Tests Reduce Cancer Mortality?
To date, no trial has shown that detecting cancers using MCD tests reduces cancer-specific mortality, the ultimate goal of any screening program.
These definitive trials are difficult to conduct due to the large study populations, extended timelines, and substantial funding requirements. However, ongoing trials such as the Falcon Study (Cancerguard), the NHS-Galleri Study, and the NCI-Vanguard Study may help determine whether these tests provide a net benefit.
Whole-Body MRI Screening: Proceed With Caution
Whole-body MRI screening is commercially available but remains controversial. There is no proven mortality benefit, and there is a significant risk of overdiagnosis and overtreatment of lesions that are benign or unlikely to affect quality of life or lifespan.
Abnormal findings often lead to additional testing and procedures, increasing costs, radiation exposure, anxiety, and the risk of complications.
What Makes a Cancer Screening Test Effective?
For any screening test to be effective, two criteria must be met:
- Early detection identifies diseases that would otherwise cause significant morbidity or mortality
- Treatment is more effective when initiated before symptoms develop
For currently recommended cancer screening tests, these criteria have been carefully evaluated and demonstrate a clear net benefit. For newer tests that have not yet undergone rigorous randomized controlled trials, the decision to pursue screening is left to the individual.
Potential Harms and Limitations of Cancer Screening
Potential harms of screening are often overlooked. False-positive results can cause emotional distress, unnecessary costs, radiation exposure, and complications from procedures. False-negative results may provide misplaced reassurance and lead individuals to skip proven screening strategies.
True-positive results can also lead to overdiagnosis or overtreatment of low-risk disease. Additionally, MCD tests cannot detect precancerous lesions, are costly, and are not currently covered by insurance.
Looking Ahead: The Future of Cancer Screening
While still in their infancy, multicancer detection tests may eventually complement existing screening strategies and be targeted to specific age groups or patients with defined risk factors or symptoms.
Of the tests reviewed, the Galleri test currently appears to be leading the field, with favorable trial results anticipated in 2026. Other emerging tests to watch include OneTest and MCaST (Quest/MD Anderson).
Continued trust in science and the scientific process, and sustained investment in research, will be essential as these technologies evolve and reshape cancer detection and prevention.
About Dr. Jose Delgado, MD
Internal Medicine at Boulder Medical Center
As an internal medicine specialist, Dr. Delgado is trained in the prevention, diagnosis, and treatment of adult diseases and has treated virtually every imaginable health condition. He is comfortable with a wide spectrum of internal medicine, from routine primary care to the management of multiple chronic diseases. Dr. Delgado enjoys treating patients from diverse backgrounds and cultures and has extensive experience treating older adults. He welcomes new patients to his practice at BMC on Broadway.
Article References
- World Cancer Research Fund. https://www.wcrf.org/
- American Cancer Society. https://www.cancer.org/
- U.S. Preventive Services Task Force. https://www.uspreventiveservicestaskforce.org/uspstf/
- Eisenstein M. Putting early cancer detection to the test. Nature. February 21, 2025. doi:10.1038/d41586-025-00530-4
- Leila MD, MPH, et al. Multicancer detection tests for screening: a systematic review. Annals of Internal Medicine. 2025;178:1591–1604. doi:10.7326/ANNALS-25-01877
- Scrag D, MD, et al. PATHFINDER: A prospective cohort study of blood-based multicancer early detection. The Lancet. October 7, 2023;402(1049):1251–1260. doi:10.1016/S0140-6736(23)01700-2
- Lennon AM, et al. Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. Science. 2020;369(6506):969–977.
doi:10.1126/science.abb9601