Development and External Validation of a Prognostic Nomogram for Metastatic Uveal Melanoma

Abstract

BackgroundApproximately 50% of patients with uveal melanoma (UM) will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM) is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians.Patients and MethodsTwo cohorts of mUM patients, from Veneto Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to develop and externally validate, a prognostic nomogram.ResultsThe median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6), and a WHO performance status=1 (HR 1.5) or 2–3 (HR 4.6) were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9). The nomogram had a concordance probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE .009) in the external validation (MC). Nomogram predictions were well calibrated.ConclusionsThe nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials.

Validation of a Prognostic Staging for Metastatic Uveal Melanoma: A Collaborative Study of the European Ophthalmic Oncology Group

“…19 We did not record the disease free interval in the present validation study, but it was not an independent prognostic factor in our building dataset. 3 A potential explanation for these differences is that the eventual true survival was not yet known for 29% of patients in the building and for 69% of patients in the validation datasets used to construct the nomogram who were either alive or were lost to follow-up at the time of analysis, 19 whereas we followed all patients until they had died and their exact survival time was known. 3 Percentages of patients assigned to stages IVa to IVc, 43%, 40% and 17% in the original M A N U S C R I P T The median observed survival for each stage likewise was longer than that in the original dataset: 17.2 vs. 14.9 months for stage IVa, 10.0 vs. 8.9 months for IVb, and 4.2 vs. 2.0 months for IVc.…”

“…The investigators who described the recent prognostic nomogram for metastatic uveal melanoma have not yet provided a comparison of predicted with observed survival times. 19 In the building dataset, 73% of patients received chemo-or chemoimmunotherapy, and 10% underwent surgical resection. 3 In the validation set, these percentages were 67% and 18%, which reflects the participation of two OOG centers in which surgery is the preferred approach to metastatic uveal melanoma.…”

“…10,18 Recently, a nomogram-based system for this purpose was developed and externally validated. 19 A previous multivariate analysis of the overall survival of 91 consecutive patients who died of metastatic uveal melanoma identified three variables -performance index reflecting general health of the patient, largest diameter of the largest metastasis (LDLM) reflecting measurable metastases, and serum alkaline phosphatase (AP) level reflecting both liver function and, indirectly, unmeasurable miliary metastases as being independently associated with survival. 3 A prognostic Helsinki University Hospital Working Formulation based on this multivariate model divides newly diagnosed metastatic (stage IV 20 ) uveal melanoma in three prognostic categories with a predicted median overall survival of either ≥12 months (IVa), <12-6 months (IVb), and <6 months (IVc).…”

“…We recommend that the validated Working Formulation 3 or the recent prognostic nomogram, 19 both of which share performance index, extent of measurable metastases and liver function tests as their basis for staging, be used for evidence-based, stage-specific reporting of survival of patients with metastatic uveal melanoma in prospective studies. …”

“…In a recent study, data of 152 patients were used to build and data from an additional 102 patients were used to validate a new nomogram-based prognostic system for metastatic uveal melanoma. 19 The nomogram includes performance status, percentage of liver involvement, lactate dehydrogenase level, and disease-free interval. The authors measured the largest diameter of liver metastases but elected not to analyze this variable because, on theoretical grounds, they considered the percentage of liver substitution to be the best indicator of the effective volume of hepatic disease.…”