P0366 - Performance of Colon and Rectal Cancer Detection with a Multi-Cancer Early Detection (MCED) Blood Test

Award: Presidential Poster Award

Matthew Margolis, MS¹, Kathryn N. Kurtzman, MD², Cheng Chen, PhD³, Jordan J.. Karlitz, MD, FACG^4
1GRAIL, LLC, Menlo Park, CA; ²GRAIL, Menlo Park, CA; ³GRAIL, Inc., Menlo Park, CA; ⁴GRAIL, LLC, Denver, CO

Introduction: A blood-based MCED test intended to complement, but not replace, recommended USPSTF screening can detect a cancer signal for multiple cancers simultaneously at a specificity of 99.5% (low false positive rate). In the case-control Circulating Cell-free Genome Atlas substudy 3 (CCGA3), MCED test performance across multiple cancer types was evaluated (Table 1). Sensitivity of cancer signal detection (CSD) for colorectal cancer (CRC) was 82.0%. As colon cancer (CC) and rectal cancer (RC) can be clinically distinct (CC is more common than RC, may be more likely to present with no/minimal symptoms, and can develop as interval cancers between colonoscopy or stool-based screenings), we provide a subanalysis of MCED test performance in CC and RC from CCGA3.

Methods: The MCED test uses a targeted methylation assay and machine learning classifier to detect a cancer signal in cell-free DNA and predict its origin.. We evaluated 197 CCGA3 participants with CRC and used pathology reports to determine tumor location (CC vs RC). Sensitivity of CSD stratified by stage and cancer type (CC vs RC) and overall survival were assessed.

Results: There was no significant difference in sensitivity between CC and RC across all stages (p≥0.05) (Figure 1). There was no significant difference in sensitivity for CC between stages II, III and IV (p≥0.05) and a significant difference at stage I (p< 0.05). No significant difference in sensitivity for RC was observed across stages (Figure 1). CRC and CC not detected by the MCED test had significantly better survival than those detected (Figure; p=0.0038 and p=0.014, respectively); however, no significant difference was found in RC (p=0.11).

Discussion: At a specificity of 99.5%, the MCED test can detect both CC and RC at earlier stages (prior to metastases). It has been shown to detect less-indolent, more aggressive disease (associated with worse survival), allowing opportunity for earlier intervention in higher-risk patients. High sensitivity for CC is especially useful as CC may be associated with fewer symptoms and more likely to present as interval cancers (potentially asymptomatic) between standard screening intervals. A study limitation is relatively low subgroup sizes. Lower sensitivity for stage I CC is explained by shallower depth of tumor invasion. In summary, high sensitivity of this MCED test allows detection of both CC and RC signals, including in those who may not be up to date with standard screening, while also detecting multiple other cancer types.




Disclosures:


Matthew Margolis, MS¹, Kathryn N. Kurtzman, MD², Cheng Chen, PhD³, Jordan J.. Karlitz, MD, FACG⁴. P0366 - Performance of Colon and Rectal Cancer Detection with a Multi-Cancer Early Detection (MCED) Blood Test, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.