Can a Blood Test Help Personalize Chemotherapy Before CRS/HIPEC?
Morgan R, Neilson T, You Y ... A prospective single-arm feasibility study using preoperative ctDNA to tailor neoadjuvant chemotherapy for patients with colorectal or appendiceal adenocarcinoma. Surgical Oncology Insight, 2026; 3
For patients with colorectal or appendix cancer that has spread to the lining of the abdomen, treatment may involve a combination of systemic chemotherapy and cytoreductive surgery (CRS), sometimes combined with HIPEC. One question doctors continue to study is how much chemotherapy patients need before surgery—and whether every patient needs the same amount.
A new study from researchers at MD Anderson Cancer Center is exploring whether a blood test called circulating tumor DNA (ctDNA) could help answer that question for some patients with colorectal or appendiceal adenocarcinoma and peritoneal metastases.
What is ctDNA?
Cancer cells can release tiny fragments of their DNA into the bloodstream. These fragments are known as circulating tumor DNA, or ctDNA. A blood test can sometimes detect this DNA and provide information about whether cancer may still be present or how the disease is behaving.
However, peritoneal metastases are somewhat different from many other types of metastatic cancer. Tumors confined to the peritoneum often release relatively little DNA into the bloodstream, meaning a patient can have known peritoneal disease and still have a negative ctDNA test. In previous research, ctDNA has been undetectable in as many as two-thirds of patients with known peritoneal metastases.
Researchers believe this limitation may actually provide useful information. If ctDNA is detectable in a patient whose visible disease appears limited to the peritoneum, it could potentially signal more aggressive cancer biology or microscopic disease elsewhere in the body that cannot yet be seen on scans.
How is the study using ctDNA?
Patients enrolled in this study first receive approximately two to three months of chemotherapy using commonly used colorectal cancer regimens. They are then evaluated again with imaging and a personalized ctDNA blood test.
The ctDNA result then helps guide the next step:
If ctDNA is undetectable and the cancer remains surgically treatable, the patient can move toward repeat evaluation and CRS, with or without HIPEC.
If ctDNA remains detectable, the patient receives another two to three months of systemic chemotherapy before surgery is considered.
The idea is to determine whether patients whose disease appears biologically lower-risk could safely proceed to surgery sooner, potentially reducing unnecessary chemotherapy and its side effects. At the same time, patients whose ctDNA suggests higher-risk disease might benefit from additional systemic treatment before undergoing a major operation.
Why could this matter for patients?
There is currently no single established answer for how long patients with colorectal or high-grade appendiceal cancer and peritoneal metastases should receive chemotherapy before CRS/HIPEC.
Longer chemotherapy can provide important cancer control, but it can also bring cumulative side effects, affect quality of life, and potentially make recovery from major surgery more difficult. On the other hand, shortening treatment too much could leave aggressive or microscopic disease inadequately treated.
A blood-based biomarker that helps doctors distinguish between these situations could move treatment toward a more personalized approach—using a patient's tumor biology, rather than a standard number of chemotherapy cycles, to help guide treatment decisions.
What has the study found?
This is where an important distinction is needed: the researchers have not yet reported whether the strategy improves recurrence or survival.
The study plans to enroll 48 patients, and only 16 had been enrolled when this article was published. Researchers will ultimately compare outcomes such as recurrence-free survival, overall survival, treatment response, and patterns of recurrence between patients with detectable and undetectable ctDNA.
The authors describe this as an early, hypothesis-generating study. Because it is a small, single-arm trial, larger randomized studies would be needed before ctDNA could be used routinely to determine how much chemotherapy a patient should receive before CRS/HIPEC.
The Takeaway
This study represents an intriguing step toward more individualized treatment for patients with colorectal or appendiceal cancer that has spread to the peritoneum.
Rather than automatically giving every patient the same duration of chemotherapy before surgery, researchers are asking whether a simple blood test could help identify who may be ready to proceed to CRS/HIPEC sooner—and who may benefit from additional systemic treatment first.
For now, ctDNA should not be viewed as a stand-alone test for determining whether peritoneal cancer is present or whether a patient should undergo surgery. But if ongoing research confirms its usefulness, ctDNA could become another tool multidisciplinary specialists use alongside imaging, pathology, surgical evaluation, disease burden, treatment response, and other factors to build a treatment plan tailored to the individual patient.
