The following transcript has been edited for clarity:
I'm Timothy Murray, MD, from Miami Ocular Oncology and Retina, and I’m updating on our presentation at the Retina World Congress 2025 in Fort Lauderdale. I spoke about the small melanoma tumor conundrum, and we used a patient series to be able to report on this. We’re focusing on a shift toward earlier treatment and the incorporation of genetic testing for good diagnostic evaluation.
This was a consecutive series of about 226 small tumor eyes. This is the largest series in the country. All eyes showed clear melanoma characteristics, and all eyes were managed with vitrectomy laser ablation, peeling of the ILM, suppression of inflammation with steroid, and gene expression profiling with a fine-needle aspiration biopsy through the Castle Biosciences program. The GEP or gene expression profiling from Castle Biosciences is a reverse transcription polymerase chain reaction (RTPCR) analysis of 15 genes. It includes a learning algorithm and a predicted classification along with discriminate value.
There was a 5-year incidence of metastasis development, and that was related to class. Class 1A tumors had a 2% incidence, class 1B had a 20% incidence, and class 2 had a 70% incidence of metastasis. So that test is really important, but that test has changed its diagnostic criteria and it has moved where the mortality rates appear to be decreasing as we're shifting to earlier treatments. So, in this series for us of 226 eyes, the age was an average of 58 years. Two hundred and twelve or 93% had a focal retinal detachment, 54% had increasing tumor size; and the entry-level vision was 20/70 with a tumor thickness of 1.8 mm.
Remarkably the mean follow-up for this study is approximately 5 years. In this study, with a single surgical approach, we saw a significant functional recovery. The tumor size dropped from 1.8 mm on average to 1.3 mm. We were able to get a diagnostic test in 99% of our patients, which is remarkable for these small tumors. And when we looked at classification, 80% of our patients were class 1A, 18% were class 1B, and 12% or 27 patients were class 2. Why is that important? Class 2 patients with a 5-year follow-up should have a mortality rate expected between 50% and 70%. And when we were able to look at our patients, we in fact saw a significant decrease in mortality. Our argument has been that early intervention for small and small-to-medium tumors makes a significant difference in survival. So, the conundrum has been the risk of vision or functional globe loss vs the risk of mortality, and the feeling was the mortality risk was low, but now we know the mortality risk is not as low as we expected, and that early intervention can change that mortality.
So, in our class 1 patients, 1% of patients had metastatic incidents at 5 years. For our class 2 patients, 4% had a metastatic incident at 5 years. That's a reduction from 20% for class 1 to 1% and from 72% for class 2 to 4%—significant reductions in mortality.
We believe that these data support a conundrum of change where we move from delayed observational treatment to early intervention. The key is to be able to establish the diagnosis of clinical small malignant melanoma, and it requires a vitreoretinal surgical approach with very focused ablation and biopsy. We are seeing significant benefits anatomically and visually for our patients. Vision improved to 20/30. In 95% of these patients the tumor shrank, they're alive and well, and we're continuing to follow this cohort of a very large series of 226 patients. Thank you. RP
