Universal cancer screening: revolutionary, rational, and realizable

Abstract

Cancer remains the second leading cause of mortality worldwide, and overall cancer-related deaths are increasing. Despite the survival benefit from early detection, screening has to date targeted only those few organs that harbor tumors of sufficient prevalence to show cost-effectiveness at population levels, leaving most cancer types unscreened. In this perspective overview, a case is made for universal cancer screening as a logical and more inclusive approach with potentially high impact. The centrally important conceptual drivers to universal screening are biological and epidemiological. The shared biology of tumor marker release into a common distant medium, like blood, can be exploited for multi-cancer detection from a single test. And, by aggregating prevalence rates, universal screening allows all cancers (including less common ones) to be included as targets, increases screening efficiency and integration across tumor types, and potentially improves cost-effectiveness over single-organ approaches. The identification of new tumor marker classes with both broad expression across tumor types and site-prediction, remarkable advances in assay technologies, and compelling early clinical data increase the likelihood of actualizing this new paradigm. Multi-organ screening could be achieved by targeting markers within or stemming from the circulation (including blood, urine, saliva, and expired breath) or those exfoliated into common excretory pathways (including the gastrointestinal and female reproductive tracts). Rigorous clinical studies in intended use populations and collaborations between academia, industry, professional societies, and government will be required to bring this lofty vision to a population application.

Projected Reductions in Absolute Cancer–Related Deaths from Diagnosing Cancers Before Metastasis, 2006–2015

“…To date, screening asymptomatic persons for cancer involves isolating single anatomic regions for imaging, direct visualization, or retrieval of abnormal cells (5). At present, three single cancer types are recommended for population-wide screening by the U.S. Preventive Services Task Force (USPSTF): breast (6), cervical (7), and colorectal (8,9).…”

The Translational Status of Cancer Liquid Biopsies

“…However, most cancers present symptomatically and are only diagnosed at difficult to treat stages. Arguably, pre-symptomatic population wide screening for early cancer detection is one of the most attractive applications of liquid biopsies and could in principle improve clinical outcomes [3]. However, this application comes with a unique set of challenges that will need to be addressed before clinical adoption.…”

“…Metastatic spread to distal sites, which is the definition of late-stage cancer, accounts for 90% of cancer-related deaths [2]. There is a case to be made that population-wide screening and early cancer detection might have a substantial positive impact on cancer morbidity and mortality [3]. Despite this need for earlier detection of cancer, screening tests with proven clinical utility are uncommon.…”

“…The half-life of ctDNA is short (2)(3)(4)(5) h in blood and urine [33,34,38]) and concentrations can decrease rapidly in response to treatment [33]. ctDNA levels are therefore useful as a monitoring biomarker [33] for estimating cancer burden in patients and assessing treatment responses.…”

Biomarkers for Early Cancer Diagnosis: Prospects for Success through the Lens of Tumor Genetics

“…As a result, the possible molecular nature of a biomarker today is as varied as there are substances in the body, and includes circulating tumoral DNA (e.g., mutated EGFR gene [ 7 ] ), the various types of RNA (particularly microRNA [ 8 ] ), peptides and proteins (e.g., hormones, receptors, antibodies), [ 9 ] lipids and other metabolites, [ 10 ] circulating tumor cells, and non‐cellular vesicles called “exosomes”. [ 11 ] There are currently great expectations (e.g., [ 12–15 ] ) that these molecular and cellular biomarkers will provide the needed specificity, sensitivity, reproducibility, and cost‐effectiveness for the early diagnosis of particular types of cancer. Here, we discuss current progress, set‐backs, misconceptions, and future promises in the development of biotechnology‐based biomarkers for early cancer detection.…”