In this article Bertil Damato, MD, PhD, FRCOphth and Sarah E. Coupland, MBBS, PhD, FRCPath review their experience in translating uveal melanoma cytogenetics into clinical practice, highlighting the hurdles and discussing the benefits that have accrued.
Initially, they believed it would be a simple matter to type uveal melanomas according to their chromosome 3 status and to manage patients accordingly. But in practice, the deployment of uveal melanoma cytogenetics at the bedside proved more difficult than expected because of technical difficulties, problems harvesting tumor samples, psychological concerns and ethical dilemmas.
They also found that cytogenetic classification of uveal melanomas into "lethal" and "nonlethal" types was insufficient for estimating risk of metastasis because prognostication also required consideration of other factors, such as: clinical tumor stage, histologic grading of malignancy and influence of age and sex on life expectancy.
They also found that metastatic deaths occurred without monosomy 3, possibly because small deletions were missed or because of tumor heterogeneity.
Still, there have been several benefits. Mainly, it allows clinicians to reassure patients with a good prognosis while targeting systemic screening at high-risk cases.
They note that some ocular oncologists are critical of predicting metastasis when such disease is essentially untreatable. However, they write that their experience has been quite different.
"Patients did not regret being given a poor prognosis, which they felt was less stressful than not being given a prognosis at all. Several patients reported that the information they were given enabled them to get their affairs in order while they still felt well. The patients with monosomy 3 seemed to be less distressed by their poor prognosis than expected, either because they had not fully grasped the implications or because they hoped that screening would prolong life or because of various other coping mechanisms. Patients given a good prognosis were obviously greatly relieved. Most needed convincing, however, that the reassurance they received was well founded. The most unhappy patients were the ones in whom biopsy failed, which is why we are now more circumspect about recommending this procedure if the tumor is small."
While some might question the ethics of performing genomic studies in the absence of sufficient evidence regarding the sensitivity and specificity of any predictions, they disagree.
"We felt that even if not infallible, genomic studies were justified as long as they improved any chances of providing an accurate prognosis. We now believe that it may be unethical to deprive patients of genomic studies, especially with small tumors, when the chances of providing reassurance are greatest."
Dr. Chévez-Barrios receives grant support from the Children's Oncology Group, which is sponsored by the National Cancer Institute.