Blood Test May Determine Which Patients With CRC Need Chemo After Surgery

Results of a blood test may help indicate which patients with colorectal cancer are at risk of relapse after surgery and should undergo chemotherapy, and which ones can skip it, according to recent research published in Nature Medicine.

The researchers measured circulating tumor DNA (ctDNA), which is cancer DNA that is found in the blood stream, in 1,039 patients with stage 2 through 4 resectable colorectal cancer. ctDNA levels were tested before and after resection (surgical removal of the cancer), and findings showed that ctDNA positivity four weeks after surgery was associated with a higher risk of disease recurrence and was the most significant prognostic factor for patients with stage 2 or 3 colorectal cancer.

“Except for BRAF and RAS status, ctDNA was observed to be the most significant risk factor for recurrence,” the researchers wrote. “This is exemplified by the fact that ctDNA-positive patients four weeks after surgery with stage 1 and low-risk stage 2 (colorectal cancer) had markedly higher rates of recurrence than ctDNA-negative patients with resected oligometastatic (colorectal cancer).”

Additionally, the findings showed that ctDNA positivity also identified which patients with stage 2 or 3 disease would benefit from post-surgical chemotherapy treatment.

Currently, clinicians use multiple factors to determine if a patient should undergo post-surgical chemotherapy treatment, such as stage, tumor size and lymphovascular invasion (the presence of cancer in the lymphatic or vascular systems).

Now, researchers hope that these findings support the use of ctDNA measurements in the treatment decision criteria. Not only would this get chemotherapy to the patients who really need it, but it could also spare patients from chemotherapy-related side effects — especially for patients with oligometastatic stage 3 colon adenocarcinoma, a patient group where data on the benefit of post-surgical chemotherapy is inconsistent.

Overall, the researchers cite that while this addition of chemotherapy has been shown to improve progression-free survival (time from treatment until disease worsens), this does not often translate to improved overall survival (time from treatment until death).

“It has been reported that standard (post-surgical chemotherapy) can decrease the absolute recurrence rate by only 10–15% in the overall population harboring clinicopathological risk factors, with side effects including oxaliplatin-induced peripheral neuropathy,” the researchers wrote. “However, clinically, the decision to administer (post-surgical chemotherapy) is frequently weighed against factors that include patient preference, patient performance status and clinical risk of recurrence.”

The researchers also explained that post-surgical treatment for patients with ctDNA positivity can be beneficial, as seen in the phase 3 IMvigor010 trial, which showed that patients with muscle-invasive bladder cancer with positive ctDNA scores after treatment experienced a decrease in ctDNA after being administered Tecentriq (atezolizumab). However, there was no Tecentriq-derived benefit for patients who were ctDNA-negative after undergoing surgery.

“…strong evidence of a similar relationship should be taken into account, and here, the similar trend reported in urothelial cancersupports our results,” the researchers wrote.

Now, continued research will look at how to best use ctDNA for patients with colorectal cancer.

“Ongoing prospective randomized trials will further investigate the optimal ctDNA-guided treatment strategy for surgically resectable CRC,” they wrote.

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