Reference
"Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications" by Dr. Tomoko Akaike, et al., Journal of Clinical Oncology.
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ctDNA Testing Helps Predict Recurrence in Merkel Cell Carcinoma
Key Takeaways
- ctDNA testing effectively stratifies Merkel cell carcinoma patients into high and low recurrence risk categories, influencing surveillance strategies.
- The study's cohorts revealed significant recurrence rate differences based on ctDNA status, even after adjusting for cancer stage and other factors.
Researchers found that some patients with Merkel cell carcinoma may benefit from less imaging if their ctDNA remains undetectable each quarter of the year.
Image generated by Adobe Firefly.
Using circulating tumor DNA (ctDNA) testing has been shown to be an accurate and prognostic biomarker as a surveillance method for patients with Merkel cell carcinoma, a type of rare skin cancer, according to a study.
The National Cancer Institute defines ctDNA as small fragments of DNA that are released into patients’ bloodstreams as tumor cells die. Taking samples of patients’ blood can help identify and measure the amount of ctDNA remaining and can determine specific DNA changes (mutations).
In the study published in the Journal of Clinical Oncology, the researchers established that ctDNA testing helped determine patients with Merkel cell carcinoma who are low-risk and do not require imaging frequently and those who are high-risk and require imaging more frequently.
The study was divided into two cohorts, which included 167 patients in the discovery cohort (group identifying any new information) and 152 patients in the validation cohort (group confirming known information).
At enrollment, 40% (66 of 167 patients) of patients in the discovery cohort had clinically evident disease, according to the study. Among these patients, 63 of the 66 patients showed ctDNA positivity. In the same cohort of patients, 96 had no signs of clinically evident disease and 86 of these patients tested negative for ctDNA.
In the validation cohort at enrollment, 41% (63 of 152 patients) showed clinically evident disease, the study stated.
Risk of Recurrence via ctDNA Status in Merkel Cell Carcinoma
During the surveillance (watching) portion of the study, 119 patients and 96 patients from the discovery and validation cohorts, respectively, underwent consecutive ctDNA testing, the researchers noted. There was a median of 91 days between receiving ctDNA tests in the discovery cohort and a median of 83 days in the validation cohort.
Of note, 24 patients in the discovery cohort experienced a recurrence (return of cancer) and two patients died after a median follow-up of 267 days. Among patients in the validation cohort, 25 experienced a recurrence, with no reported deaths within the follow-up of 194 days.
“The risk of recurrence was significantly higher in patients who were ctDNA-positive at any point during surveillance compared with those who remained ctDNA-negative in both the discovery cohort and the validation cohort,” the researchers wrote in the study.
READ MORE: Jimmy Buffet Had Merkel Cell Carcinoma, a Cancer That ‘Strikes Fear in the Hearts of Many’
Differences in recurrence among the groups with ctDNA positivity and negativity were significant when adjusting for certain factors, the researchers noted. These factors included cancer stage, immunosuppression status (immune system functionality), sex and age in the discovery and validation cohorts, respectively.
Predicting Cancer Recurrence Through ctDNA Testing
In both the discovery and validation cohorts, patients experienced a gradual increase in positive prediction value, which helped determine a prediction for recurrence, according to the study. A negative prediction value was reported to be high at 4.5 months (135 days) after having a negative ctDNA test in either cohort and remained high at 5.9 months (180 days).
“National guidelines recommend surveillance imaging for high-risk patients and as clinically indicated for others but do not specify an interval in either population,” the researchers wrote. “The results of our study support using ctDNA to guide imaging frequency in patients under surveillance after treatment of Merkel cell carcinoma.”
READ MORE: Mohs Surgery Offers ‘Survival Advantage’ in Early Merkel Cell Carcinoma
They also noted that having a high negative prediction value of 93% at 135 days of follow-up reassured patients and doctors that the Merkel cell carcinoma would likely not recur after three to four months.
“Considering this, it may be reasonable to forgo imaging if ctDNA remains undetectable quarterly,” they wrote.
Post-Treatment ctDNA Status for Patients With Merkel Cell Carcinoma
An analysis within the study included 84 patients who had undergone ctDNA tests within four months following a curative-intent surgery or radiation. Twenty-three of the 84 patients experienced recurrences with no reported deaths within a follow-up of 314 days.
At the time of post-treatment, 14 patients were ctDNA-positive and had significantly higher recurrence rates compared with 70 patients who were ctDNA-negative. Researchers reported that significant differences in recurrence occurred after adjusting factors for cancer stage, immunosuppression status, sex and age.
“At 12 months, the recurrence-free probability was 9% among patients with a positive ctDNA at any time during surveillance, compared with 91% for patients who remained ctDNA-negative,” the researchers wrote. “In our patient cohort, ctDNA outperformed traditional recurrence risk factors in its ability to distinguish between stage 1 to 3 patients who are more likely to be cured by surgery and radiation therapy and those likely to recur.”
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