The Current State of Multicancer Screening with Blood Tests: Scientific Facts and Uncertainties
In this article
Multicancer Screening with a Blood Test
Early detectionis one of the most critical factors determining survival and treatment success in cancer. Developed in recent years, multicancer detection (MCD) testsaim to detect, from a single blood sample, multiple cancers . A review published on 16 September 2025in Annals of Internal Medicineprovides a comprehensive systematic reviewshedding light on these tests’ benefits, accuracy and potential harms. The conclusion? For now, they are not ready for routine screening.
🔬 How Do These Tests Work?
MCD tests analyze tumor-derived biomarkers in the bloodstream:
- Cell-free DNA (cfDNA) and methylation signatures
- Protein and metabolite panels
- Genomic sequencing and the interpretation of hundreds of markers using machine learning
The test usually reports ‘cancer signal detected/not detected’ . If the result is positive , further investigations identify which organ or which cancer is involved — the risk of a false positive here may lead to unnecessary imaging and invasive procedures.
📊 Figures from the Review (20 studies, 109,177 people)
A total of 19 different tests were examined. Accuracy measures varied over a wide range:
| Measure | Range | Comment |
|---|---|---|
| Sensitivity | 0.095 – 0.998 | High for some tests; others are close to random guessing in performance. |
| Specificity | 0.657 – 1.0 | The risk of false positives varies from test to test. |
| AUC | 0.52 – 1.0 | Performance is highly variable; not all tests are the same. |
A key nuance: In prediagnostic studies resembling real screening settings, sensitivity/AUC is lower. The high accuracy reported in case-control designs involving people already diagnosed with cancer cannot be generalized to screening in practice.
⚠️ Why Are They Not Ready for ‘Routine Screening’?
- No evidence of benefit: No controlled study has yet shown that MCD screening reduces mortality .
- Low PPV: Positive predictive value is often below 50% → a substantial proportion of positive results are not cancer.
- Risk of replacing routine screening: A negative MCD result may lead to mammography/colorectal screening and other standard screening being neglected .
- Regulatory status: No FDA approval; some tests are available only as a laboratory-developed test (LDT) .
🧩 Potential Harms and Effects on Clinical Practice
- False positive → unnecessary imaging, biopsy, cost and anxiety
- False negative → false reassurance and delayed diagnosis
- Burden on the healthcare system → more than half of those with positive results may not have cancer
The review found that evidence on patients’ adherence to standard screening and complications during diagnostic procedures after MCD was limited . Ongoing studies will clarify this area.
🧭 A Clinical Road Map: How Should We Approach This for Now?
- Do not neglect standard screening: Age- and risk-appropriate mammography, colorectal screening, cervical screening and so on remain the top priority .
- Shared decision-making: With people considering an MCD test, openly discuss PPV/NPV, false results, the follow-up burden and the balance of benefit and uncertainty .
- Uncertain target population: Even with a high familial/hereditary risk, an evidence-based role for MCD has not yet been defined.
- Experimental setting: Where possible, consider testing within a clinical trial ; otherwise, do not recommend it routinely .
❓ Frequently Asked Questions
My result was negative. Can I feel reassured? — To some extent. NPV is generally high, but MCD does not cover all cancers. Age- and risk-appropriate standard screening must continue.
My result was positive. Does this definitely mean cancer? — No. For many tests, PPV is below 50%. Confirmation with additional imaging and, when necessary, biopsy is required; the likelihood of a false positive is high.
Do these tests replace standard screening? — No. MCD may, at best, be added to mammography/colorectal/cervical screening in the future, not as a replacementbut alongside it . Replacing standard screening is not currently recommended.
Who might consider it? — Individuals with high anxiety or an interest in research may consider it within a clinical trial . Even with high familial risk, evidence for routine use is insufficient.
What is the FDA approval and availability status? — There is no FDA approval. Some tests are offered only as a laboratory-developed test (LDT) ; their performance has not been established in a screening setting.
Are there ongoing studies? — Yes. Large-scale controlled trials are ongoing. Their results are awaited to see a reduction in mortality and other real benefits .
📚 Source
- Kahwati LC, Avenarius M, Brouwer L, et al. Multicancer Detection Tests for Screening: A Systematic Review. Annals of Internal Medicine. 16 September 2025. doi: 10.7326/ANNALS-25-01877
Was this article helpful?
Your feedback helps us improve our content.
Reader comments
Share your comment
Your name and comment are published only after administrator approval. Your email address is never shown to visitors.
Be the first to comment.