A personalized blood test can predict which patients with colorectal cancer (CRC) who have undergone surgery, will benefit from adjuvant chemotherapy treatment (ACT) post-surgery, without compromising survival outcomes.

The study was conducted on over 1000 CRC patients using a custom-built circulating tumor DNA (ctDNA) test for monitoring treatment and assessing molecular residual disease (MRD) in patients diagnosed with cancer. The personalized blood test called Signatera MRD was developed by Natera, a company that focuses on cell-free DNA testing for oncology.

Most high-risk CRC patients are automatically recommended for chemotherapy after surgery to clear any residual cancer cells and reduce risk of relapse. However, earlier studies have shown only 30% CRC patients benefit from chemotherapy post-surgery, 50% of them being already cured by the surgery, while 20% experience disease recurrence despite additional chemotherapy.

The new test, if incorporated into the care guidelines for CRC, could potentially spare patients the unnecessary pain of additional chemotherapy while reducing the burden on the healthcare system. The findings were published as the cover story in the journal Nature Medicine on January 16, 2023 “Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer.”

“Until now, oncologists did not have adequate tools to determine which colorectal cancer patients are likely to benefit from adjuvant systemic therapy,” said Takayuki Yoshino, MD, PhD, of the National Cancer Center Hospital East, Kashiwa, Chiba, Japan and the study’s principal investigator. “This study provides strong evidence that Signatera MRD-positive patients will benefit significantly from adjuvant therapy, while MRD-negative patients may be safely observed, regardless of clinical or pathological stage.”

The ctDNA findings reported are from the observational GALAXY arm of the ongoing CIRCULATE-Japan study (UMIN000039205). The study analyzed pre- and post-surgical ctDNA in 1,039 patients with operable, stage II-IV CRC. In this group of patients, the investigators found the presence of ctDNA at around four weeks was linked with higher risk of relapse and constituted the most significant prognostic factor associated with risk of recurrence in patients with stage II or III CRC.

Essentially, the study shows patients who were MRD-positive four weeks after surgery (18%) derived significant benefit from ACT while patients who were MRD-negative (82%) did not see significant benefit from the treatment.

“Post-surgical ctDNA positivity identified stage II/III patients who derived benefit from ACT,” the authors noted. “Our study represents one of the largest and most comprehensive prospective analysis of ctDNA in resectable CRC, supporting the use of ctDNA testing to identify patients who are at increased risk of recurrence and are likely to benefit from ACT.”

Minetta Liu, MD, chief medical officer of oncology at Natera said, “We are proud to partner with the CIRCULATE consortium and look forward to making Signatera accessible to all colorectal cancer patients in the U.S., Japan, and worldwide.”

The National Cancer Care Network (NCCN) is expected to incorporate these findings into its guidelines for CRC in 2023. This step would represent the translation of precision medicine into clinical care with the potential of improving outcomes for patients. The findings also add to the budding field of fragmentomics that focuses on circulating DNA, particularly  in the context of cancer screening.

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