Liquid biopsy for colorectal cancer may guide therapy for tumors

A new study from the University of Washington School of Medicine in St. Louis shows that a liquid biopsy examining blood or urine may help assess the effectiveness of therapy for colorectal cancer that has just begun to spread beyond the original tumor. This biopsy can detect persistent disease and can serve as a guide for deciding whether a patient should undergo further treatment due to some tumor cells escaping an initial attempt to eradicate cancer.

The study appears online on February 12 at Journal of Clinical Oncology Precision Oncology, a journal of the American Society of Clinical Oncology.

Although some liquid biopsies have been approved by the Food and Drug Administration, mainly for lung, breast, ovarian and prostate cancer, none have been approved for colorectal cancer.

The patients in this study had what is known as oligometastatic colorectal cancer, which means that each patient’s cancers have spread beyond their original tumor, but only to a small number of sites. These patients undergo chemotherapy to shrink tumors before surgery to remove what is left of the primary tumor. There is debate in the field about whether, after initial therapy, oligometastatic cancer should be treated as metastatic cancer, with more chemotherapy – or as localized cancer, with more surgery and radiation in these limited locations.

Contributing to the problem is that doctors have a limited ability to predict how patients will respond to early chemotherapy, especially since most patients do not have access to cancer genome sequencing to identify DNA mutations in their original tumors.

“Being able to measure response to early chemotherapy without prior knowledge of tumor mutations is a new and important idea for being able to determine whether the patient responded well to therapy,” said senior author Aadel A. Chaudhuri, MD, Ph. D., assistant professor of radiation oncology. “This can provide guidance on how to treat oligometastatic disease. For example, if a liquid biopsy indicates that a patient responded well to early chemotherapy, perhaps the possibility of further surgery should be offered, which could potentially cure the disease. They did not respond. well, the cancer is likely to be very widespread and cannot be eradicated with surgery, so these patients should receive more chemotherapy to control their disease. “

Liquid biopsies for colorectal cancer detect the DNA of the tumor that has been released from the cancer and is circulating in the blood and, to a lesser extent, was collected in the urine. The biopsies described in this study are unique compared to other liquid biopsies developed for colorectal cancer in three main ways. First, most of these biopsies were developed to screen for metastatic cancers or to verify that local cancers have not started to spread. Second, most liquid cancer biopsies are based on knowledge of the mutations of the original tumor, to see if those mutations are still present in the blood after therapy. But many patients do not have the opportunity to sequence their original tumors. Instead, the new biopsies depend on detecting DNA mutations in the blood or urine and comparing them with the DNA mutations measured in the treated primary tumor, after being surgically removed. And finally, urine biopsy is exclusive to colorectal cancer, as most urine biopsies have been limited for use in cancers of the genitourinary system, especially bladder cancer.

“The levels of circulating tumor DNA that we were able to measure in urine were lower than we measured in blood, but this is still proof of concept that it is possible to measure residual disease in non-urinary cancer in this totally non-invasive way,” said Chaudhuri , who also treats patients at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “We need to develop more sensitive techniques to detect colorectal tumor DNA in the urine to make this a useful clinical test. But this is a promising start.”

The study showed that lower levels of circulating tumor DNA correlated with better responses to early chemotherapy. In fact, most patients who had undetectable levels of tumor DNA in blood samples also did not have measurable cancer in their surgical samples.

There was also evidence that the residual disease detected in liquid biopsies was more predictive of results than the residual disease found in surgical specimens. For example, the researchers described the experience of a man who, after early chemotherapy to reduce or eliminate the tumor, still had the detectable cancer removed during surgery. But his blood sample collected on the same day showed no circulating tumor DNA. He experienced long-term survival without cancer recurrence. On the other hand, it was found that a woman with no detectable cancer cells in her surgical sample, removed after early chemotherapy, had circulating tumor DNA in her blood sample from the same day. Eight months later, the cancer returned to his liver.

The study suggests that these liquid biopsies may help to personalize the treatment of oligometastatic colorectal cancer. In addition to identifying patients at high risk of recurrence and helping to guide decisions about which traditional therapies should be administered, the new study also identified patients who could benefit from immune therapies and other targeted treatments.

“Based on the mutations in the blood biopsy, we can identify patients who can benefit from a type of immune therapy called immune control point inhibitors after initial therapy is complete,” said Chaudhuri. “We also found mutations that could target targeted drugs approved for other types of cancer. Our current study is observational, but it paves the way for the design of future clinical trials that can test some of these potential therapies.”

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More information:
Pellini et al. Detection of MRD ctDNA and personalized oncogenomic analysis in colorectal and urine colorectal cancer. JCO Precision Oncology. February 12, 2021.