Validating the Helsinki University Central Hospital (HUCH) working formulation for staging metastatic uveal melanoma

Purpose: To validate the Helsinki University Central Hospital (HUCH) Working Formulation, the first substaging system designed to predict prognosis of metastatic uveal melanoma and to facilitate design, reporting and interpretation of controlled clinical trials. Methods: Data of 226 patients who died of disseminated uveal melanoma were collected from members of the European Ophthalmic Oncology Group (OOG). Karnofsky or WHO performance status, largest diameter of largest metastasis and serum alkaline phosphatase (AP) level at diagnosis of metastases, and time to death were requested. The working formulation is based on a multivariate model that identified these variables as independent predictors of survival, modeling time on chemotherapy as a confounding variable (Eskelin et al. Cancer 2003; 97: 65–75). Patients whose predicted survival was less than 6 months were assigned to stage IVc, between 6 and 12 months to stage IVb and over 12 months to stage IVa. Observed survival time was calculated for each stage. Results: The median AP level was 0.69 (range, 0.24-11) times upper normal limit, median largest metastasis was 3.5 cm (range, 0.8-19), and percentage of patients representing WHO performance index 0, 1-2 and 3 was 61%, 38% and 1%, respectively. Of the 226 patients, 100 (44%) were assigned to stage IVa, 97 (43%) to IVb and 29 (13%) to IVc. The median observed survival times were 18.3, 10.0 and 4.6 months, respectively. In Kaplan-Meier analysis, the stages reflected best to worst survival (P<0.0001, log-rank test for trend). Conclusions: The collaborative OOG study confirms the HUCH Working Formulation as a repeatable, valid system for dividing patients with metastatic uveal melanoma into groups of differing prognosis.