Gut Microbiome Test Predicts Melanoma Recurrence After Surgery

Melanoma remains prone to relapse even after surgery and adjuvant immunotherapy, with 25% to 40% of patients experiencing recurrence. Clinicians lack reliable pre-treatment indicators to identify those at highest risk, and improved risk stratification could better guide surveillance and treatment decisions. New findings now show that gut microbiome “fingerprints” can predict melanoma recurrence with up to 94% accuracy.

NYU Langone Health and its Perlmutter Cancer Center evaluated a microbiome “fingerprint” approach that analyzes the specific mix of intestinal bacteria to stratify recurrence risk. The work centers on the gut microbiome, whose constituents help train immune responses and may influence how patients respond to immunotherapies. Investigators identified bacterial groups most associated with changes in recurrence risk, including Eubacterium, Ruminococcus, Firmicutes, and Clostridium.

The method reads the sequence of DNA building blocks from all bacterial species present in stool, generating presence-absence profiles for each patient. Because predictive taxa can vary by geography, the team first matched patients by the overall similarity of their gut microbiomes and then derived region-appropriate signatures. Using a standard measure of microbial similarity, a signature built from North American patients accurately predicted recurrence in other regions, but only when patients shared a comparable microbial “fingerprint.”

Study analyses included 674 patients with resected melanoma enrolled in the global CheckMate 915 clinical trial. After surgery, participants received adjuvant immunotherapy—either nivolumab plus ipilimumab or nivolumab alone—across five geographic regions: North America, Eastern Europe, Western Europe, Australia, and the rest of the world. The gut microbiome remained remarkably stable during a year-long course of immunotherapy.

Across regions, the approach predicted recurrence with accuracies ranging from 83% to 94%, and up to 94% when patients were analyzed with the matching strategy. The findings were published in Cell on April 17. The research was provided by NYU Langone Health and conducted through its Perlmutter Cancer Center.

“Past studies have struggled because the gut bacteria that predict treatment success seemed to change from one region to another. Our study provides a new method that overcomes this barrier, showing that these markers are indeed generalizable if we account for the person's underlying microbiome,” said Jiyoung Ahn, Ph.D., professor in the Department of Population Health at NYU Grossman School of Medicine and associate director of Population Research at NYU Langone’s Perlmutter Cancer Center.

“This means that a single pre-treatment microbiome test could provide a reliable forecast of a patient's risk. The next step is to validate this matching approach in other cancers and to build the diverse databases needed to make this approach clinically feasible. In the future, we envision analyzing a patient's microbiome before treatment, comparing it to a global database, and providing a reliable prognosis that guides therapy from the start,” said Richard Hayes, DDS, MPH, Ph.D., professor in the Department of Population Health at NYU Langone.

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