• How Useful Is PRAME Testing in Choroidal Melanoma?


    Two ocular oncologists debated the benefits and drawbacks of a new prognostic test for choroidal melanoma during the Friday Ocular Oncology and Pathology Subspecialty Day “Pro/Con Debates” session (Pth02V). Preferentially expressed antigen in melanoma, or PRAME, is a cancer-test antigen that is overexpressed in melanoma and is typically a marker of poor outcomes. Up first, Zélia M. Corrêa, MD, PhD, explained why she favors testing for PRAME.

    Improved prognostic testing accuracy. In class 1 and class 2 uveal melanoma, PRAME testing improves the accuracy of prognostic testing. For example: Class 1 PRAME-positive tumors carry a 31% to 38% risk of metastasis over a five-year period, which drops to 0% to 5% for PRAME-negative tumors.

    Improved chromosomal testing accuracy. PRAME enables physicians to better distinguish which patients have better odds of progression-free survival or disease-free survival.

    Expression tied to outcomes. PRAME expression is associated with increased aneuploidy, which can drive tumor progression, including chromosome copy number variations such as 6p gain, 6q loss, 8q gain, and 16q loss.

    Therapeutic target. PRAME is quickly becoming an important companion prognostic test in uveal melanoma, indicating which patients may be candidates for PRAME-based targeted molecular therapy.

    “PRAME is, without a doubt, the most important new prognostic biomarker in uveal melanoma since the gene expression profile test,” Dr. Corrêa concluded. Next, Carol L. Shields, MD, provided her views on PRAME.

    Current testing might suffice. Dr. Shields questioned whether more information on prognostication is better or necessary. Is it worth the extra cost? Current DNA/RNA testing, which samples for chromosomes 1, 6, and 8, might suffice, she argued.

    Personalized prognosis with DNA. Currently, there are 52 different cytogenetic profiles for uveal melanoma (based on chromosomes 3, 6, and 8). The hazard ratio for metastasis within these profiles ranges from 1 to 123.

    Use the TCGA instead. Dr. Shields explained that The Cancer Genome Atlas (TCGA) is a simple and highly predictive classification for uveal melanoma. Four classifications enable physicians to easily prognosticate melanoma using DNA analysis of chromosomes 1, 3, 6, and 8.

    Dr. Shields, who made liberal use of graphics in her talk—and at one point likened PRAME to a “souped-up” Lamborghini—explained that she already has all the tools she needs to treat uveal melanoma. Know your tools and how best to use them, she advised. “I have one hammer in my toolbox. I don’t need two hammers or three hammers,” she said. “It may not make you a better carpenter.”

    The final verdict from the audience? Dr. Shield’s argument was apparently persuasive, winning a convincing 59% of the final vote.  —Keng Jin Lee, PhD

    Watch the Retina Subspecialty Day. If you are registered for AAO 2020 Virtual, you have access to the archived presentations on the virtual meeting platform until Feb. 15, 2021. Log in to the virtual platform. Next, from the Lobby screen, select “Sessions” from the top navigation; click “Agenda” from the drop-down menu; and click on the “Friday” tab.  

    Financial disclosures. Dr. Corrêa: Castle Biosciences: C; Immunocore: C. Dr. Shields: Aura Biosciences: C; Immunocore: C.

    Disclosure key. C = Consultant/Advisor; E = Employee; L = Speakers bureau; O = Equity owner; P = Patents/Royalty; S = Grant support.

    Read more news from AAO 2020 Virtual.