Disclosures: GRAIL Inc. funded this study. Klein reports a consultant role with GRAIL. Please see the study for all other authors’ relevant financial disclosures.
June 25, 2021
3 min read
Save

‘New paradigm’ for screening? Blood test shows accuracy for early cancer detection

Disclosures: GRAIL Inc. funded this study. Klein reports a consultant role with GRAIL. Please see the study for all other authors’ relevant financial disclosures.
You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

A blood-based test demonstrated efficacy and high specificity in detecting multiple cancer types with diverse biological features, paving the way for a new screening option, according to research published in Annals of Oncology.

Developed by GRAIL Inc., the multicancer early detection (MCED) test — which researchers said not only accurately detected cancer signals across more than 50 cancer types, but did so often before symptoms arose — will be made available in the U.S. by prescription and to complement existing screening tests following final results of the prespecified, large-scale, clinical validation substudy of the Circulating Cell-free Genome Atlas (CCGA) study.

A blood-based test demonstrated efficacy and high specificity in detecting multiple cancer types with diverse biological features.
Data were derived from Klein EA, et al. Ann Oncol. 2021;doi:10.1016/j.annonc.2021.05.806.

“The goal is to improve the way we screen for cancer,” Eric A. Klein, MD, chairman of the Glickman Urological & Kidney Institute and staff member at Taussig Cancer Institute at Cleveland Clinic, told Healio.

Eric A. Klein, MD
Eric A. Klein

“There are only five established screening tests: colonoscopy for colon cancer, mammography for breast cancer, Pap smears for cervical cancers, PSA for prostate cancer, and low-dose CT for those at high risk [for] lung cancer,” Klein continued. “Compliance with these recommended screening tests is less than 100% and, furthermore, most cancer deaths come from cancers for which there are no established screening tests. This blood test addresses those shortcomings because it’s simple to obtain and detects many cancers that are not currently detectable before symptoms develop.”

The prospective, observational CCGA study, launched in 2016 and funded by GRAIL, aimed to develop assays for early detection of cancer in blood through deep sequencing of circulating cell-free nucleic acids.

In total, the CCGA study included 15,254 participants from 142 clinics in North America, with researchers collecting biological samples from those with a new diagnosis of cancer (n = 8,584) and from those without cancer (n = 6,670). CCGA was broken into three prespecified substudies: discovery, training and validation, and clinical validation.

This third and final CCGA substudy examined the performance of the methylation-based MCED test among 4,077 participants (with cancer = 2,823; without cancer = 1,254) in an independent validation cohort. Researchers measured specificity, sensitivity and cancer signal origin prediction accuracy.

Results showed the MCED test had a specificity of 99.5% (95% CI, 99-99.8) and overall sensitivity of 51.5% (95% CI, 49.6-53.3) for cancer signal detection. Additionally, the sensitivity increased with disease stage, from 16.8% (95% CI, 14.5-19.5) for stage I to 40.4% (95% CI, 36.8-44.1) for stage II; 77% (95% CI, 73.4-80.3) for stage III and 90.1% (95% CI, 87.5-92.2) for stage IV.

The MCED test detected cancer signals across more than 50 different cancer types.

Klein told Healio that highlights of the results included stage I to stage III sensitivity of 67.6% (95% CI, 64.4-70.6) in 12 prespecified cancers that account for approximately two-thirds of U.S. cancer deaths annually, compared with stage I to stage III sensitivity of 40.7% (95% CI, 38.7-42.9) in all cancers.

Results of a post hoc analysis showed sensitivity for solid tumors without screening options, including pancreatic, liver and esophageal cancers, was almost double that for solid tumors with screening options, including breast colorectal, cervical and prostate cancer (65.6% vs. 33.7%). For hematologic malignancies, researchers reported a sensitivity of 55.1%.

Klein also noted the MCED test had a very low false-positive rate of 0.5%.

Excluding patients with an unknown origin, the overall accuracy of cancer signal origin prediction was 88.7% (95% CI, 87-90.2).

“These results set the stage for a new paradigm of screening individuals for multiple cancers with a single blood test, as opposed to the current situation where we screen for individual cancers,” Klein said. “It is intended as a supplement to currently recommended screening tests.”

Klein added there was “a lot more to come” as they continue to gather data from large, prospective studies in the U.S. and U.K. and examine the test’s feasibility for screening populations.

“These data add to a growing body of literature that supports the use of next-generation sequencing for the detection of cell-free DNA in blood samples as a tool for earlier detection of common cancers that account for a significant number of deaths and other health problems worldwide,” Klein said in the press release. “A screening test that requires only a simply blood draw could provide an option for communities that have poor access to medical facilities. I’m excited about the potential impact this approach will have on public health.”

For more information:

Eric A. Klein, MD, can be reached at Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Ave., Mail Code Q10-1, Cleveland, OH 44195; email: kleine@ccf.org.