Novel Tissue-Free MRD Assay Shows Promise in Colorectal Cancer Management

New data presented at the 2025 European Society for Medical Oncology GI Congress (ESMO GI) highlight the robust performance of a tissue-free molecular residual disease (MRD) assay, Latitude, in patients with resectable colorectal cancer (CRC).¹

Developed by Natera, this innovative diagnostic tool demonstrated excellent overall clinical utility, including high sensitivity and specificity for recurrence detection, strong prognostic capabilities, and significant predictive value for adjuvant chemotherapy benefit. The findings suggest that this liquid biopsy-based approach could play a pivotal role in refining treatment strategies and surveillance protocols for patients with CRC, particularly when tumor tissue is unavailable for analysis.

“This study demonstrates strong clinical potential for Natera’s tissue-free MRD assay,” said Yoshiaki Nakamura, MD, PhD, principal investigator of the study, in a press release. “We clearly observed the prognostic and predictive value of the assay, seeing [a] strong correlation of recurrence risk and adjuvant treatment outcomes.”

The assay's performance was rigorously evaluated in a cohort of approximately 200 patients, involving over 1300 plasma samples. These samples were derived from the GALAXY arm of the CIRCULATE-Japan study, a large-scale prospective investigation focused on MRD testing in resectable CRC. Such a comprehensive study design underscores the clinical relevance and generalizability of the results.

A key strength of the tissue-free molecular residual disease assay was its notable ability to detect cancer recurrence. In the critical postsurgical MRD window, the assay achieved 58% sensitivity, which increased to 81% in the surveillance setting. Importantly, the median diagnostic lead time for recurrence detection was 4.6 months, allowing clinicians a crucial advantage in identifying relapse earlier than conventional methods.

Complementing this sensitivity, the assay exhibited high clinical specificity, reporting 92% at the patient level and 97% at the sample level in the surveillance setting. This high specificity is vital to minimize false positives, thereby reducing unnecessary patient anxiety and overtreatment.

Beyond recurrence detection, the tissue-free molecular residual disease assay proved to be a highly prognostic indicator of recurrence risk. Patients who tested positive for MRD after surgery, both within the immediate MRD window and during ongoing surveillance, faced significantly inferior outcomes. The hazard ratios were substantial (HR, 10, P <.001 for the MRD window; HR, 18, P <.001 for the surveillance window), underscoring the assay's power to stratify patients by risk. This prognostic capability can guide clinicians in identifying patients who may require closer monitoring or more intensive treatment.

Among high-risk patients with stage II and stage III CRC, those who were MRD-positive following surgery demonstrated a significant clinical benefit from adjuvant chemotherapy (P <.001). Conversely, MRD-negative patients in the same high-risk categories did not show a statistically significant treatment benefit from adjuvant chemotherapy (P =.54). This finding has profound implications for personalized medicine in CRC, offering the potential to deescalate or intensify adjuvant chemotherapy based on individualized MRD status, thereby optimizing treatment efficacy while minimizing unnecessary toxicities for patients unlikely to benefit.

“These results reinforce the data previously presented at ASCO GI, where our tissue-free Latitude MRD assay demonstrated high overall concordance to Signatera as well as strong standalone clinical performance,” said Alexey Aleshin, MD, corporate chief medical officer and general manager of oncology at Natera, in the press release. “When offered alongside Signatera, our tissue-free assay gives patients and providers the latitude to get a reliable MRD assessment even when tissue is unavailable.”

REFERENCE:

Natera presents data at ESMO GI on its tissue-free Latitude™ MRD* assay, demonstrating excellent overall performance in colorectal cancer. News release. Natera, Inc. July 7, 2025. Accessed July 7, 2025. https://tinyurl.com/3ubc4ydh