Multicancer early detection blood test preferentially detects high-grade prostate cancer

The methylation-based multicancer early detection (MCED) Galleri blood test demonstrated the ability to preferentially detect high-grade, clinically significant prostate cancer without overdetection of indolent disease, according to findings recently published in JCO Precision Oncology.¹

The median tumor methylated fraction was higher among detected cases vs nondetected cases.

The data were previously presented at the 2024 American Association for Cancer Research Annual Meeting in San Diego, California.

"All screening tests run the risk of overdiagnosis. In the case of prostate cancer, this is largely due to the high prevalence of low-grade, indolent cancers," said lead author Brandon Mahal, MD, a radiation oncologist at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Florida, in a news release on the findings.² “The results of this study demonstrate that the use of MCED tests in a population-based screening program is unlikely to contribute to overdiagnosis of slow-growing prostate cancers that may not need treatment. That being said, clinically validated MCED tests like Galleri reveal that when a prostate cancer signal is detected, it usually indicates aggressive disease and additional diagnostic evaluation is necessary."

For the study, the investigators collected data from 420 patients from substudy 3 of the Circulating Cell-Free Genome Atlas (CCGA) trial (NCT02889978) and 18 patients from the PATHFINDER trial (NCT04241796). The median age among patients in each trial was 65 years.

In the substudy 3 CCGA data, the test sensitivity was 11.2% (47/420). In PATHFINDER, the episode sensitivity was 5.6% (1/18). Notably, the test detected no grade group 1 cancers, 1.9% of grade group 2 cancers, and 4.2% of stage 1 and stage 2 cancers across both studies combined.

Specifically, in the CCGA data, the test detected 0% (0 of 58) of grade group 1 cancers, 1.9% (3 of 157) of grade group 2 cancers, 3.2% (3 of 95) of stage 1 cancers, and 4.7% (11 of 235) of stage 2 cancers. Data in PATHFINDER were similar, with no detection of grade group 1-2 or stage 1-2 cases.

According to the authors, “These results are unsurprising given the preponderance of early-stage disease (79% stage I or II) in these 2 studies and previous observations that cfDNA concentrations in men with localized [prostate cancer] are low and similar to concentrations in healthy individuals without cancer.”¹

Rather, data from the study indicated that the test preferentially detected high-grade, clinically significant prostate cancer, with 93% of detected cancers being GG3-5 and 67% being stage 3 or 4. Among detected cancers, the cancer signal origin (CSO) prediction accuracy was 91.5% (43/47).

Specifically, the test detected 5.1% (4 of 78) of grade group 3 cancers, 31.9% (36 of 113) of grade group 4 and 5 cancers, 14.9% (7 of 47) of stage 3 cancers, and 81.5% (22 of 27) of stage 4 cancers in the CCGA dataset. In PATHFINDER, 33% (1 of 3) of grade group 3-5 cases and 50% (1 of 2) of stage 3-4 cases were detected.

Findings also showed that the median tumor methylated fraction (TMeF) was higher among detected cases vs nondetected cases (PPM, 2,106.0; IQR, 349.8-24,376.3 vs. PPM, 24.4; IQR, 17.8-38.5; P < .05). TMeF was also correlated with serum PSA levels in the detected cases (Spearman's rank correlation coefficient, r = 0.42).

The investigators also compared overall survival (OS) data to expected OS estimates from the SEER database. Compared with these estimates, nondetected cases had an approximately 3 times better OS (HR, 0.263; 95% CI, 0.104 to 0.533; P < .05), and detected cases had a similar OS (HR, 0.672; 95% CI, 0.323 to 1.21; P = .2) in accordance with age, grade group, and stage.

Senior author Eric A. Klein, MD, a Distinguished Scientist at GRAIL, concluded in the news release, “This prostate cancer analysis underscores the power of Galleri in a general population of men at-risk for prostate cancer as it is able to detect biologically significant cancers that need treatment without potentially contributing to the burden of overdiagnosis. The very high accuracy of the CSO prediction for prostate cancer indicates the need for a prompt diagnostic work-up in those with a cancer signal detected."²

References

1. Mahal BA, Margolis M, Hubbell E, et al. A targeted methylation–based multicancer early detection blood test preferentially detects high-grade prostate cancer while minimizing overdiagnosis of indolent disease. JCO Precis Oncol. 2024. doi:10.1200/PO.24.00269

2. Results of GRAIL's Galleri multi-cancer early detection blood test in prostate cancer published in JCO Precision Oncology. News release. GRAIL, Inc. August 29, 2024. Accessed August 30, 2024. https://www.prnewswire.com/news-releases/results-of-grails-galleri-multi-cancer-early-detection-blood-test-in-prostate-cancer-published-in-jco-precision-oncology-302234482.html