Validation of a Prognostic Staging for Metastatic Uveal Melanoma: A Collaborative Study of the European Ophthalmic Oncology Group.
OBJECTIVE
To validate a staging system for metastatic uveal melanoma that will facilitate planning, reporting, and interpreting the results of clinical trials.


METHODS
Reliability and validity study.


METHODS
The performance index, the largest diameter of the largest metastasis and alkaline phosphatase level at the time of diagnosis of metastases, and overall survival of 249 patients from 7 ocular oncology centers who died of dissemination were analyzed. Predicted median survival time calculated according to the Helsinki University Hospital Working Formulation was used to assign patients to stages IVa, IVb, and IVc, which correspond to predicted survival times of ≥12, <12-6, and <6 months, respectively. The predictions were compared against observed survival.


RESULTS
The 3 variables used to assign stage were independent predictors of survival in the validation dataset. Of the 249 patients, 110 (44%), 109 (44%), and 30 (12%) were classified to Working Formulation stages IVa, IVb, and IVc, respectively. Corresponding median observed survival times were 18.6, 10.7, and 4.6 months and worsened by increasing stage (P < .001). Of 201 patients managed without surgical resection of metastases, 83 (41%), 89 (44%), and 29 (15%) were classified to stages IVa, IVb, and IVc, respectively, and their median observed survival times were 17.2, 10.0, and 4.6 months (P < .001). Survival of 47 patients who underwent resection did not differ by working formulation stage (P = .69).


CONCLUSIONS
This multicenter study confirms that the Working Formulation is a reliable and valid, repeatable system for dividing metastatic uveal melanoma into distinct prognostic subgroups, especially for stage-specific reporting of survival in prospective clinical trials.
Ocular Oncology Service, Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address: tero.kivela@helsinki.fi.
Tero T
TT
Kivelä
Department of Medical Oncology, Institut Curie, Paris, France.
Sophie
S
Piperno-Neumann
Department of Ocular Oncology, Institut Curie, Paris, France.
Laurence
L
Desjardins
Department of Hematology and Medical Oncology, Charité, Berlin, Germany.
Alexander
A
Schmittel
Department of Ophthalmology, Charité, Berlin, Germany.
Nikolaos
N
Bechrakis
Department of Ophthalmology, University of Padova, Padova, Italy.
Edoardo
E
Midena
Department of Oncology, University Hospital, Lausanne, Switzerland.
Serge
S
Leyvraz
Hopital Jules Gonin, University Hospital, Lausanne, Switzerland.
Leonidas
L
Zografos
Department of Ophthalmology, Croix-Rousse Hospital and Centre Léon Bérard, Lyon, France.
Jean-Daniel
JD
Grange
Department of Ophthalmology, Croix-Rousse Hospital and Centre Léon Bérard, Lyon, France.
Guillaume
G
Ract-Madoux
Clatterbridge Centre for Oncology, Bebington, Wirral, Merseyside, United Kingdom.
Ernest
E
Marshall
St Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom.
Bertil
B
Damato
Ocular Oncology Service, Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Sebastian
S
Eskelin
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000473:pathology* / Q000556:secondary*; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods / Q000592:standards; D011237:Predictive Value of Tests; D011379:Prognosis; D012044:Regression Analysis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016019:Survival Analysis; D014604:Uveal Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000556:secondary*; D000098943:Uveal Melanoma
D000469:Alkaline Phosphatase