Is Early Detection of Cancer with Circulating Biomarkers Feasible?

Abstract

Early cancer detection before metastasis in asymptomatic patients is one of the primary objectives of cancer research initiatives. Early detection generally means more opportunities for intervention that ultimately lead to improvement in patient outcomes. Many studies have concluded that early detection of breast cancer in women older than 50 years with mammogram screening programs improves survival by 20%–25% (1). Patients with stage I ovarian cancer detected by transvaginal ultrasound (approximately 42-mm mean tumor diameter) have a 5-year survival rate of 93%, compared with 30% for patients with stage III to stage IV disease at diagnosis (2). Many blood-based biomarker tests are routinely used in clinical practice for cancer surveillance, therapy monitoring, prognosis, and risk stratification. Most experts, however, would agree that there are no blood-based biomarkers suitable for population screening or early diagnosis of cancer, despite the considerable intellectual and financial efforts worldwide. The majority of potential biomarkers fail the initial phases of the biomarker evaluation process and never make it to the clinic (3). The list of requirements for a circulating-biomarker test for early cancer detection is lengthy (4). The test must have adequate diagnostic sensitivity and specificity. In addition, the test must be inexpensive and safe if it is to be applied to mass populations. Other important criteria include analytic reproducibility and sufficient lead time. Lead time is defined as the time between asymptomatic cancer still localized to the organ of origin and clinical diagnosis. Aggressive cancers have shorter lead times than indolent cancers. Ultimately, the utility of a circulating-biomarker test for early cancer detection depends on the evidence that its benefits, such as patient survival, outweigh its harms, such as overdiagnosis and lead time bias. Overdiagnosis is often followed by overtreatments that themselves can have serious consequences with respect to patients' health. Lead time bias …