MCED Blood Test Shows Utility for Surveillance in Cancer Survivors

Performance of a targeted methylation-based multicancer early detection (MCED) test (Galleri) in cancer survivors is comparable to that in the general population, according to new data from the PATHFINDER study (NCT04241796) published in JCO Precision Oncology.¹ These findings suggest that blood-based MCED testing may help address the significant "survivorship gap" in long-term surveillance by detecting both second primary cancers and late recurrences that are often missed by current standard-of-care (SOC) guidelines.

The prospective study, led by Catherine R. Marinac, PhD, and colleagues, analyzed 1609 cancer survivors who were at least 3 years post-diagnosis and had no current suspicion of cancer. The cohort represented a subset of the 6662 participants in the broader PATHFINDER trial. Investigators found that the MCED test’s performance metrics—including positive predictive value (PPV) and specificity—did not differ significantly between those with a history of cancer and those without, providing clinical validation for the use of liquid biopsy in this high-risk population.

Key Performance Metrics

A cancer signal was detected in 1.2% (n = 20/1609) of the survivor cohort. Following diagnostic workup, 10 new cancer diagnoses were confirmed in 9 patients, resulting in a PPV of 50.0% (95% CI, 26.0%–74.0%).¹ This PPV is nearly identical to the 42.7% observed in participants without a history of cancer in the same study. Specificity remained high at 99.3%, ensuring that the rate of false positives was minimized—a critical factor for reducing the "diagnostic odyssey" in survivors already prone to health-related anxiety.

Of the 10 cancers detected, 5 were second primary cancers and 5 were recurrences. Notably, the second primaries included a stage I uterine cancer, stage II sarcoma, and stage III ovarian cancer, while the recurrences were all late-stage breast cancer occurring 4 to 11 years after the original diagnosis.

Addressing the Surveillance Gap

The US is currently home to an estimated 18.6 million cancer survivors, a number projected to exceed 22 million by 2035.²^,³ While these individuals face an elevated risk of developing new or recurrent malignancies, clear evidence-based guidance for long-term surveillance is often lacking once they move past the initial 5-year window of intensive follow-up.

Current screening guidelines from the US Preventive Services Task Force (USPSTF) only cover a handful of cancer types, such as breast, cervical, colorectal, and lung cancers.⁴ In the Marinac et al study, 80% of the second primary and recurrent cancers detected by the MCED test were types for which no standard USPSTF grade A or B screening currently exists.¹

Clinical Implementation and Workup

For clinicians, the efficiency of the diagnostic workup following a "signal detected" result is a primary concern. The study reported a median time to diagnostic resolution of just 13 days in the survivor group. This rapid turnaround was facilitated by the test’s "cancer signal origin" (CSO) feature, which predicted the anatomical location of the malignancy with high accuracy, thereby guiding targeted imaging and biopsies.

The most common previous cancers in the cohort were breast (47%), melanoma (10%), and prostate (9%). The average time since the original diagnosis was 11.2 years, highlighting the test’s utility in a long-term survivor population.

Limitations and Future Directions

While the results are promising, the authors noted that the MCED test is intended to complement, not replace, existing standard-of-care screenings. Furthermore, the study was not powered to assess the impact of MCED testing on overall mortality. Further longitudinal research is required to determine if early detection via methylation-based testing translates into improved survival outcomes for this specific patient population.

REFERENCES

1. Marinac CR, O'Donnell EK, Clarke CA, et al. Multicancer early detection blood test performance in cancer survivors from the PATHFINDER study. JCO Precis Oncol. 2025;9:e2500498. doi:10.1200/PO-25-00498

2. New ACS Study: Number of Cancer Survivors in the U.S. Reaches 18.6 Million. News release. American Cancer Society. May 30, 2025. Accessed December 22, 2025. https://pressroom.cancer.org/Cancer-Survivors-Increase

3. Miller KD, Nogueira L, Devasia T, et al. Cancer treatment and survivorship statistics, 2022. CA Cancer J Clin. 2022;72(5):409-436. doi:10.3322/caac.21731

4. A and B Recommendations. US Preventive Services Task Force. Accessed December 22, 2025. https://tinyurl.com/5yavkuuw