Multi-cancer detection and localization for more than 50 cancer types

The early detection of cancer improves outcomes for patients – in terms of both reducing treatment burden and improving the chances of a cure. Screening programs are used for many common cancer types across the globe, including cervical, breast, colon and lung. However, uptake and compliance with these screening programs vary, and cancer diagnoses are often made when patients are symptomatic with later stage disease.

The possibility of a blood-based screen to detect multi-cancer types using circulating tumor cell-free DNA (cfDNA) represents an exciting potential step-change in the early detection of cancers. A prospective case-control sub-study, recently published in the Annals of Oncology assessed the use of a targeted methylation analysis of cfDNA to detect multiple cancer types, as well as the tissue of origin.1 The Circulating Cell-free Genome Atlas (CCGA) study (NCT02889978) included 6689 participants, of which 2482 were known to have one of 50 cancer subtypes and 4207 of participants without cancer.

VJOncology caught up with one of the co-authors of the paper, Eric Klein, MD, from the Glickman Urology & Kidney Institute, Cleveland, OH. In this interview, Prof. Klein reviews the rationale of this study, the main outcomes, the potential impact and next steps. This interview was recorded via an online conference call with The Video Journal of Oncology (VJOncology).

Prof. Klein comments that ‘the point of this study, the CCGA, was to exploit new technology, next-generation sequencing, to try and develop a liquid biopsy – a blood test – that samples all of the organs in the body at the same time, and determine whether or not we might be able to detect the presence of early-stage cancers, particularly those that are highly lethal but don’t have established screening paradigms’.

The study reported a high specificity of 99.3% (95% CI 98.3–99.8) with a low false-positive rate of 0.7%. The sensitivity in detection of cancers stage I–III was 67.3% (95% CI 60.7–73.3%) in 12 cancer types – anal, bladder, colon/rectum, esophageal, head and neck, liver/bile-duct, lung, lymphoma, ovarian, pancreatic, plasma cell neoplasm and stomach. The sensitivity across all cancer types was 43.9% (95% CI 39.4–48.5%). Detection sensitivity increased with cancer stage, and the tissue of origin was predicted in 96% of samples, and accurate in 93%.

These are exciting results, and the potential benefits of this study could have a huge impact on the early detection of multiple cancers.

In the interview, Prof. Klein highlights that ‘the next steps are further validation studies in larger patient populations’. These include the PATHFINDER study (NCT04241796), which is enrolling 70% of patients from an elevated risk group, including history of smoking, genetic cancer predisposition or history of hematological malignancy, and the rest from a non-elevated risk group.

Following this further validation work, Prof. Klein comments that ‘the ultimate goal, if it works, would be to make this available as a widescale screening test for the adult population, with or without, known risk factors for cancer’.


  1. Liu MC, Oxnard GR, Klein EA, et al. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol. 2020 Mar;