Dr Shoushtari on the Promise and Current Limitations of ctDNA Monitoring in Uveal Melanoma

“We need to incorporate [ctDNA monitoring] into trials, and we need to prove that these decisions are as good, if not better, than using our scans.”

Alexander N. Shoushtari, MD, an associate attending physician at Memorial Sloan Kettering Cancer Center, discussed the growing interest in circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) monitoring across solid tumor oncology and where it currently stands in metastatic uveal melanoma.

Broadly across solid tumor oncology, motivations are rising to check for cfDNA method for finding residual disease, Shoushtari said. Metastatic uveal melanoma is one of the better-studied scenarios in which cfDNA could be helpful, though the approach remains limited: not every patient has detectable ctDNA or cfDNA at baseline, he noted. Testing for this can often be useful when considering the use of agents such as tebentafusp-tebn (Kimmtrak), where patients can benefit even when a scan shows little shrinkage or a slight increase in the size of some lesions, according to Shoushtari.

Where the field needs to go, Shoushtari explained, is to incorporate ctDNA monitoring into trials and prove that decisions based on its results are as good as, if not better than, those based on imaging. He noted that work is still lagging, and it is difficult to accomplish, adding that demonstrating this would require a large study in which ctDNA serves as a primary or co-primary end point. Although other investigators are incorporating the approach, he and his colleagues are largely using it as an embedded secondary aim.

The harder goal, Shoushtari said, is to use ctDNA contemporaneously in a large phase 3 trial and returning results to investigators and patients in real time, as quickly as a CT scan or MRI, so they can make a better decision together. That real-time application has been missing in uveal melanoma management, and not for lack of trying, he added.

Until high-quality data establish that ctDNA results are more actionable than those from RECIST-based imaging, Shoushtari said he cannot use ctDNA testing universally in his own practice. Although he explained that it can sometimes be useful, he countered that at other times, the scans speak for themselves, as does the trajectory of patients’ symptoms. As a result, the field remains in a heterogeneous situation without clear guidance mandating the use of ctDNA monitoring, he concluded, though it is valuable to have available for select cases.