Figure 4.

Balancing sensitivity and specificity in the cfDNA-based liquid biopsy model

The optimal cutoff value for the cfDNA-based liquid biopsy model should be determined based on different clinical sensorias ahead of its application in the intended-use population. For example, specificity is more important when PPV is taking into consideration in screening assay with cancer of a low prevalence. Assuming that the prevalence for a certain cancer in the general population is 1%, at 90% specificity and 90% sensitivity, the PPV is 8.3%, indicating that a true patient with cancer has been detected, with 11 false positives. If the specificity is increased from 90% to 99%, the PPV is dramatically increased to 47.6%. Comparatively, if the sensitivity increases from 90% to 99%, the PPV is mildly increased to 9.1%. However, under several scenarios, such as early detection in cancers that have specific high-risk factors or convenient diagnostic procedures, cfDNA test with high sensitivity and mild specificity is more acceptable. We propose a simplified formula for consideration to minimize the extra socioeconomic burden. Sen, sensitivity; Spe, specificity.