The goal of earlier cancer detection is to identify the disease at a stage when it can be effectively treated, thereby offering the patient a better chance of long-term survival. Adherence to screening modalities known to decrease cancer mortality such as colonoscopy, mammography, low-dose computed tomography, and Pap smears varies widely. Moreover, the majority of cancer types are diagnosed only when symptoms occur. Multicancer blood tests offer the exciting possibility of detecting many cancer types at a relatively early stage and in a minimally invasive manner.

Evaluation of the feasibility and safety of multicancer blood testing requires prospective interventional studies. We designed such a study to answer four critical questions: (i) Can a multicancer blood test detect cancers not previously detected by other means? (ii) Can a positive test result lead to surgical intervention with curative intent? (iii) Can testing be incorporated into routine clinical care and not discourage patients from undergoing recommended screening tests such as mammography? (iv) Can testing be performed safely, without incurring a large number of unnecessary, invasive follow-up tests?

We evaluated a blood test that detects DNA mutations and protein biomarkers of cancer in a prospective, interventional study of 10,006 women who were 65 to 75 years old and who had no prior history of cancer. Positive blood tests were followed by diagnostic positron emission tomography–computed tomography (PET-CT), which served to independently confirm and precisely localize the site and extent of disease if present. The study design incorporated several features to maximize the safety of testing to the participants.

Of the 10,006 enrollees, 9911 (99.1%) could be assessed with respect to the four questions posed above. (i) Detection: Of 96 cancers incident during the study period, 26 were first detected by blood testing and 24 additional cancers by conventional screening. Fifteen of the 26 patients in whom cancer was first detected by blood testing underwent PET-CT imaging, and 11 patients developed signs or symptoms of cancer after the blood test that led to imaging procedures other than PET-CT. The specificity and positive predictive value (PPV) of blood testing alone were 98.9% and 19.4%, respectively, and combined with PET-CT, the specificity and PPV increased to 99.6% and 28.3%. The blood test first detected 14 of 45 cancers (31%) in seven organs for which no standard-of-care screening test is available. (ii) Intervention: Of the 26 cancers first detected by blood testing, 17 (65%) had localized or regional disease. Of the 15 participants with positive blood tests as well as positive PET-CT scans, 9 (60%) underwent surgery with curative intent. (iii) Incorporation into clinical care: Blood testing could be combined with conventional screening, leading to detection of more than half of the total incident cancers observed during the study period. Blood testing did not deter participants from undergoing mammography, and surveys revealed that 99% of participants would join a similar, subsequent study if offered. (iv) Safety: 99% of participants did not require any follow-up of blood testing results, and only 0.22% underwent an unnecessary invasive diagnostic procedure as a result of a false-positive blood test.

A minimally invasive blood test in combination with PET-CT can safely detect and precisely localize several types of cancers in individuals not previously known to have cancer, in some cases enabling treatment with intent to cure. Further studies will be required to assess the clinical utility, risk-benefit ratio, and cost …