Detecting Cancer Years Before Diagnosis: The Rise of Blood-Based Screening

Conventionally, a cancer diagnosis was only possible when symptoms appeared, and images and biopsies revealed abnormalities. By this point, the cancer may have already progressed to an advanced stage, making it difficult, if not impossible, to treat. As such, the resulting poor prognosis is often associated with cancer’s low survival rates. In a groundbreaking new study, researchers developed liquid biopsies that can measure certain molecular markers in the blood, making cancer detection possible years before a clinical diagnosis.

Cancer cells release fragments of genetic material and other biomarkers into the bloodstream as they grow and divide. These biomarkers include circulating tumor DNA (ctDNA), which carries fragments of DNA with mutations specific to a tumor; altered DNA methylation patterns, which the way in which methyl groups are added to DNA; circulating tumor cells, which break away from the original tumor and can grow to form new tumors; and cancer-associated proteins (Wan et al., 2017). While these signatures are expressed at minimal levels in early-stage disease, advances in next-generation sequencing and bioinformatics allow these signatures to be identified with increasing sensitivity.

Liquid biopsies work by analyzing a routine blood sample for these cancer-specific markers. Compared to traditional biopsies, which are highly invasive and involve the collection of tissue samples from all suspicious areas, liquid biopsies are minimally invasive and can be repeated over time, making them well-suited for early detection and longitudinal monitoring (Heitzer et al., 2019). Certain studies have found that ctDNA can be detected years before a tumor becomes clinically apparent. This finding indicates that cancer development can leave a molecular footprint long before actual symptoms surface.

CancerSEEK, a type of blood test, aims to identify eight common types of cancer by examining ctDNA mutations and protein biomarkers. These cancers include ovarian, liver, and pancreatic carcinoma, for which there are currently no effective screening tests. This novel blood test demonstrated a median sensitivity of approximately 70% across all cancer types, with specificity of over 99%, suggesting that there were very few false positives (Cohen et al., 2018). Although detection sensitivity varied significantly between cancer type and stage, the study established blood screening as a reliable method to identify cancer biomarkers.

Additional evidence corroborating the proficiency of blood tests comes from retrospective analyses that use stored blood samples. Researchers at Johns Hopkins University examined plasma samples collected years before cancer diagnosis, and they found that ctDNA could be detected up to three years before clinical detection in some patients, suggesting that tumors release detectable DNA early in their development (Phallen et al., 2017).

More recently, large multi-cancer early detection (MCED) programs have expanded on the concept of early cancer detection with blood tests. The Circulating Cell-free Genome Atlas (CCGA) study analyzed DNA methylation patterns in blood samples to detect and localize more than 50 cancer types. The study’s results show a specificity of 99.5% and an overall sensitivity that increased with cancer stage, reaching the highest accuracy for aggressive and deadly cancers (Liu et al., 2020). The test was also able to predict the tissue of origin and most positive cases, addressing key challenges in previous multi-cancer screening procedures.

The success of these studies rely on highly sensitive sequencing techniques capable of detecting rare, tumor-derived DNA fragments among millions of normal DNA fragments. To achieve this goal, blood samples are first processed to isolate the plasma from which cell DNA is extracted and sequenced. Subsequently, machine learning algorithms are used to distinguish
cancer-associated patterns from normal biological variation, allowing for rigorous cancer screening (Wan et al., 2017).

Longitudinal or retrospective research designs are common, in which blood samples collected years prior are matched to eventual cancer diagnoses. This approach allows researchers to determine when cancer biomarkers first occur and to assess how effectively blood-based screening would function in a practical setting. However, because early-stage cancers shed minuscule amounts of DNA, obtaining high sensitivity remains a challenge, particularly for indolent cancers, which are characterized by slow-growing early tumors.

Although liquid biopsy technology has evolved rapidly, it still needs to overcome major challenges prior to widespread adoption. The possibility of overdiagnosis, uncertainty about how to manage positive results, and lack of equitable access to testing are just a few examples.

Additionally, other active areas of debate include cost, follow-up imaging, and ethical considerations about detecting cancers that may never cause harm within a patient’s lifetime. As of now, the majority of blood-based screening tests are not a part of routine clinical care for the general population. Regulatory approval has also so far been limited to specific clinical uses, such as monitoring treatment response or detecting minimal residual disease. Nonetheless, several tests are currently undergoing large prospective trials to determine whether early detection through blood screening leads to improved survival rates and reduced cancer mortality.

The ability to detect cancer earlier could fundamentally reshape the field of oncology. Earlier detection typically means simpler treatments, fewer side effects, and significantly higher survival rates. On a population level, blood-based screening can complement existing screening programs and fill gaps for cancers that currently lack effective early detection methods.
Scientifically, these findings represent an enhanced understanding of cancer biology through a review of how early tumors evolve and interact with the body. As technology improves, liquid biopsies could become a cornerstone of preventative medicine, shifting cancer care from late-stage treatment to early intervention and long-term disease prevention.

Blood-based cancer screening is one of the most promising advances in oncology. By detecting molecular traces of cancer before symptoms appear, liquid biopsies have the potential to transform cancer care. Although further validation, exploration, and research, as well as a carefully organized implementation, are needed, the growing body of evidence suggests early detection through blood testing may soon become a powerful tool in our fight against cancer.


References

Cohen, J. D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., Douville, C., Javed, A. A., Wong, F., Mattox, A., Hruban, R. H., Wolfgang, C. L., Goggins, M. G., Dal Molin, M., Wang, T.-L., Roden, R., Klein, A. P., Ptak, J., Dobbyn, L., & Schaefer, J. (2018). Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science, 359(6378), 926–930. https://doi.org/10.1126/science.aar3247
Heitzer, E., Haque, I. S., Roberts, C. E. S., & Speicher, M. R. (2018). Current and future perspectives of liquid biopsies in genomics-driven oncology. Nature Reviews Genetics, 20(2), 71–88. https://doi.org/10.1038/s41576-018-0071-5
Liu, M. C., Oxnard, G. R., Klein, E. A., Swanton, C., Seiden, M. V., Cummings, S. R., Absalan, F., Alexander, G., Allen, B., Amini, H., Aravanis, A. M., Bagaria, S., Bazargan, L., Beausang, J. F., Berman, J., Betts, C., Blocker, A., Bredno, J., Calef, R., & Cann, G. (2020). Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Annals of Oncology, 31(6).
https://doi.org/10.1016/j.annonc.2020.02.011
Wan, J. C. M., Massie, C., Garcia-Corbacho, J., Mouliere, F., Brenton, J. D., Caldas, C., Pacey, S., Baird, R., & Rosenfeld, N. (2017). Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nature Reviews. Cancer, 17(4), 223–238. https://doi.org/10.1038/nrc.2017.7