What role do blood tests play in cancer screening?

Blood Tests in Cancer Screening: Limited Role with Specific Exceptions

Blood tests currently play a very limited role in cancer screening for the general population, with the notable exception of PSA testing for prostate cancer (which remains controversial), and they are not recommended as standalone screening tools for most cancers. 1

Current Evidence-Based Blood Tests in Cancer Screening

Prostate-Specific Antigen (PSA) Testing

• PSA blood testing (alone or with digital rectal examination) detects prostate cancer at earlier stages than no screening, but evidence regarding mortality benefit remains conflicting and experts disagree about its value. 1
• The American Cancer Society recommends shared decision-making for PSA screening rather than routine testing, as men whose cancer is detected through screening may be treated without definite expectation of benefit. 1
• PSA testing can lead to false-positive results causing sustained anxiety, and abnormal results require prostate biopsies that can be painful and lead to complications like infection or bleeding. 1

Tumor Markers: Not Recommended for General Screening

• Traditional tumor biomarkers like CA 125 for ovarian cancer and AFP for hepatocellular cancer lack sufficient sensitivity and specificity for population-based screening. 1, 2
• CA 125 is elevated in only half of early ovarian cancers and can be increased by noncancerous gynecological diseases and other conditions, making it unsuitable as a screening test. 1
• No organization currently recommends screening average-risk women for ovarian cancer with blood tests due to lack of efficacy evidence. 1

Stool-Based Tests: The Blood Test Exception

Fecal Occult Blood Testing (FOBT) and Fecal Immunochemical Tests (FIT)

• For colorectal cancer screening, stool blood tests (FOBT and FIT) are the only blood-detection tests with proven mortality reduction, decreasing colorectal cancer deaths by 15-33% when performed properly. 1, 3
• These tests detect occult blood in stool, not blood circulating in the body, and must be performed as annual 3-day home testing with 2-3 samples from consecutive bowel movements—never as a single office test after digital rectal examination. 1, 3
• High-sensitivity FIT tests are preferred over guaiac-based tests because they require no dietary restrictions, have fewer false positives, and show better patient adherence. 1, 3

Critical Quality Requirements

• Any stool blood test must detect the majority of prevalent cancers at the time of testing—tests with unacceptably low sensitivity should not be offered to patients. 1
• Single-sample office FOBT has an unacceptably low sensitivity of only 4.9% for advanced neoplasia and 9% for cancer, yet 31.2% of physicians still use this inadequate method. 3
• All positive stool blood tests require follow-up colonoscopy, not repeat stool testing. 1, 3

Emerging Multi-Cancer Detection Blood Tests

Current Status: Not Ready for Clinical Use

• Multi-cancer early detection (MCED) blood tests are under investigation but are not yet validated or recommended for routine screening by any major guideline organization. 4, 5
• The National Comprehensive Cancer Network notes that false positives from multi-cancer detection tests can lead to unnecessary additional testing and patient anxiety. 4
• These tests show promise in preliminary studies with high specificity, but further validation is required before incorporation into general population screening. 5, 6

Why Blood Tests Have Limited Screening Utility

Fundamental Limitations

• Lack of sensitivity and specificity remains the consistent challenge—when combined with low prevalence of specific cancers in asymptomatic populations, most blood biomarkers produce unacceptable rates of false positives and false negatives. 7, 2
• The risk of overdiagnosis is particularly concerning, whereby lesions of no clinical consequence may be detected, creating difficult management decisions and exposing patients to treatment morbidity without benefit. 7
• No specific acceptance threshold for sensitivity or specificity has been established for cancer screening tests, but expert consensus requires that tests detect the majority of prevalent cancers. 1

Established Screening Alternatives

• The American Cancer Society recommends colonoscopy as the gold standard for colorectal cancer because it allows both detection and prevention through polyp removal. 4
• Traditional imaging-based screening (mammography for breast cancer, Pap tests for cervical cancer) remains the recommended approach for their respective cancer types. 4
• Structural tests like colonoscopy, flexible sigmoidoscopy, and CT colonography can detect both cancer and precancerous polyps, offering prevention opportunities that blood tests cannot provide. 1

Common Pitfalls to Avoid

• Never use FOBT as a diagnostic test for hospitalized patients with suspected GI bleeding—it is designed and validated only for outpatient colorectal cancer screening, not for diagnosing active bleeding. 8
• Never accept single-sample office FOBT as adequate screening—this practice provides false reassurance and wastes resources with sensitivity of only 4.9% for advanced disease. 3
• Never order tumor markers like CA 125 or CEA for cancer screening in asymptomatic average-risk individuals—these tests lack evidence of mortality benefit and lead to unnecessary workups. 1, 2
• Avoid rehydration of guaiac-based FOBT slides, as this substantially increases false positive rates without improving cancer detection. 3