Abstract
Purpose
To determine the clinical factors that influence survival in patients with metastatic uveal melanoma.
Study design
Single-center, retrospective review of patients’ medical records.
Methods
The following data of ninety-nine consecutive patients (49 men, 50 women) with metastatic uveal melanoma were registered: patient demographics; primary tumor characteristics; features of first melanoma-related metastasis; symptoms and patient status at distant disease debut and metastasis treatment. Overall survival was analyzed by Kaplan-Meier estimates. A Cox proportional hazards regression model was applied to identify independent predictors associated with survival.
Results
Mean patient age at metastatic diagnosis was 60.7 years (standard deviation, 12.8). The liver was the first metastatic site in most (92.9%) cases. The median disease-free interval was 26 months (interquartile range, 34). Median overall survival after detection of the first metastasis was 8 months (interquartile range, 14). The baseline characteristics of the primary uveal melanoma were not associated with survival in patients with stage IV disease. In the multivariate analysis, the following factors at first metastatic diagnosis were associated with improved overall survival: disease-free interval > 36 months; better performance status; and normal serum lactate dehydrogenase and gamma glutamyl transpeptidase levels. Overall survival was not influenced by specific metastatic treatment.
Conclusion
Although metastatic uveal melanoma has a poor prognosis, this study reveals the existence of several independent prognostic factors for prolonged overall survival. These findings may help improve survival estimates in patients with advanced disease.
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References
Egan KM, Seddon JM, Glynn RJ, Gragoudas ES, Albert DM. Epidemiologic aspects of uveal melanoma. Surv Ophthalmol. 1988;32:239–51.
Virgili G, Gatta G, Ciccolallo L, Capocaccia R, Biggeri A, Crocetti E, et al. Incidence of uveal melanoma in Europe. Ophthalmology. 2007;114:2309–15.
Caminal JM, Ribes J, Clèries R, Ibañez N, Arias L, Piulats JM, et al. Relative survival of patients with uveal melanoma managed in a single center. Melanoma Res. 2012;22:271–7.
Bishop KD, Olszewski AJ. Epidemiology and survival outcomes of ocular and mucosal melanomas: a population-based analysis. Int J Cancer. 2014;134:2961–71.
Shields C, Furuta M, Thangappan A, Nagori S, Mashayekhi A, Lally DR, et al. Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol. 2009;127:989–98.
Lorigan J, Wallace S, Mavligit G. The prevalence and location of metastases from ocular melanoma : imaging study in 110 patients. AJR AM J Roentgenol. 1991;157:1279–81.
Group COMS. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma. Arch Ophthalmol. 2005;123:1639–43.
Buder K, Gesierich A, Gelbrich G, Goebeler M. Systemic treatment of metastatic uveal melanoma: review of literature and future perspectives. Cancer Med. 2013;2:674–86.
Agarwala SS, Eggermont AMM, O’Day S, Zager JS. Metastatic melanoma to the liver: a contemporary and comprehensive review of surgical, systemic, and regional therapeutic options. Cancer. 2014;120:781–9.
Gragoudas ES, Egan KM, Seddon JM, Glynn RJ, Walsh SM, Finn SM, et al. Survival of patients with metastases from uveal melanoma. Ophthalmology. 1991;98:383–9.
Eskelin S, Pyrhönen S, Hahka-Kemppinen M, Tuomaala S, Kivelä T. A prognostic model and staging for metastatic uveal melanoma. Cancer. 2003;97:465–75.
Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118:1881–5.
Harbour JW, Chao DL. A molecular revolution in uveal melanoma: implications for patient care and targeted therapy. Ophthalmology. 2014;121:1281–8.
Kaliki S, Shields C, Shields J. Uveal melanoma: estimating prognosis. Indian J Ophthalmol. 2015;63:93–102.
Valpione S, Moser J, Parrozzani R, Bazzi M, Mansfield S, Mocellin S, et al. Development and external validation of a prognostic nomogram for metastatic uveal melanoma. PLoS One. 2015;10:e0120181.
Kivelä T, Piperno-Neumann, Desjardins L, Schmittel A, Bechrakis N, Midena E, et al. Validation of a prognostic staging for metastatic uveal melanoma: a collaborative study of the European ophthalmic oncology group. Am J Ophthalmol. 2016;168:217–26.
Group COMS. Assessment of metastatic disease status at death in 435 patients with large choroidal melanoma in the Collaborative Ocular Melanoma Study (COMS): COMS report no. 15. Arch Ophthalmol. 2001;119:670–6.
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. Malignant melanoma of the uvea. In: Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. 7th edn. New York: Springer; 2010:547–59.
Group COMS. Design and methods of a clinical trial for a rare condition. Control Clin Trials. 1993;14:362–73.
Group COMS. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report no. 28. Arch Ophthalmol. 2006;124:1684–93.
Caminal JM, Mejia K, Masuet-Aumadell C, Arias L, Piulats JM, Guitérrez C, et al. Endoresection versus iodine-125 plaque brachytherapy for the treatment of choroidal melanoma. Am J Ophthalmol. 2013;156(334–42):e1.
Caminal JM, Padrón-Pérez N, Arias L, Masuet-Aumatell C, Gutiérrez C, Piulats JM, et al. Transscleral resection without hypotensive anaesthesia vs iodine-125 plaque brachytherapy in the treatment of choroidal melanoma. Eye. 2016;30:833–42.
Kivelä T, Puusaari I, Damato B. Transscleral resection versus iodine brachytherapy for choroidal malignant melanomas 6 millimeters or more in thickness: a matched case-control study. Ophthalmology. 2003;110:2235–44.
Garcia-Arumi J, Leila M, Zapata MA, Velázquez D, Dinares-Fernandez MC, Tresserra F, et al. Endoresection technique with/without brachytherapy for management of high posterior choroidal melanoma: extended follow-up results. Retina. 2015;35:628–37.
Rajpal S, Moore R, Karakousis C. Survival in metastatic ocular melanoma. Cancer. 1983;52:334–6.
Bedikian AY, Legha SS, Mavligit G, Carrasco CH, Khorana S, Plager C, et al. Treatment of uveal melanoma metastatic to the liver: a review of the M. D. Anderson Cancer Center experience and prognostic factors. Cancer. 1995;76:1665–70.
Rietschel P, Panageas K, Hanlon C, Patel A, Abramson D, Chapman P. Variates of survival in metastatic uveal melanoma. J Clin Oncol. 2005;23:8076–80.
Kodjikian L, Grange J-D, Baldo S, Baillif S, Garweg JG, Rivoire M. Prognostic factors of liver metastases from uveal melanoma. Graefes Arch Clin Exp Ophthalmol. 2005;243:985–93.
Pons F, Plana M, Caminal JM, Pera J, Fernandes I, Pérez J, et al. Metastatic uveal melanoma. Melanoma Res. 2011;21:217–22.
Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, et al. Screening for metastasis from choroidal melanoma: The Collaborative Ocular Melanoma Study Group Report 23. J Clin Oncol. 2004;22:2438–44.
Chattopadhyay C, Kim DW, Gombos DS, Oba J, Qin Y, Williams MD, et al. Uveal melanoma: from diagnosis to treatment and the science in between. Cancer. 2016;122:2299–312.
Callejo SA, Antecka E, Blanco PL, Edelstein C, Burnier MN. Identification of circulating malignant cells and its correlation with prognostic factors and treatment in uveal melanoma. A prospective longitudinal study. Eye. 2007;21:752–9.
Blanco PL, Lim LA, Miyamoto C, Burnier MN. Uveal melanoma dormancy: an acceptable clinical endpoint? Melanoma Res. 2012;22:334–40.
Sosa MS, Bragado P, Aguirre-Ghiso JA. Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat Rev Cancer. 2014;14:611–22.
Eskelin S, Pyrhönen S, Summanen P, Prause J, Kivelä T. Screening for metastatic malignant melanoma of the uvea revisited. Cancer. 1999;85:1151–9.
Choudhary MM, Gupta A, Bena J, Emch T, Singh AD. Hepatic ultrasonography for surveillance in patients with uveal melanoma. JAMA Ophthalmol. 2016;134:174–80.
Augsburger JJ, Corrêa ZM, Trichopoulos N. Surveillance testing for metastasis from primary uveal melanoma and effect on patient survival. Am J Ophthalmol. 2011;152:5–9.
Hendler K, Pe’er J, Kaiserman I, Baruch R, Kalickman I, Barak V, et al. Trends in liver function tests: a comparison with serum tumor markers in metastatic uveal melanoma (part 2). Anticancer Res. 2011;31:351–7.
Mouriaux F, Diorio C, Bergeron D, Berchi C, Rousseau A. Liver function testing is not helpful for early diagnosis of metastatic uveal melanoma. Ophthalmology. 2012;119:1590–5.
Chen LL, Tian JJ, Su L, Jing Y, Zhang SC, Zhang HX, et al. DJ-1: a promising marker in metastatic uveal melanoma. J Cancer Res Clin Oncol. 2015;141:315–21.
Kaiserman I, Amer R, Pe’Er J. Liver function tests in metastatic uveal melanoma. Am J Ophthalmol. 2004;137:236–43.
Hsueh EC, Essner R, Foshag LJ, Ye X, Wang H-J, Morton DL. Prolonged survival after complete resection of metastases from intraocular melanoma. Cancer. 2004;100:122–9.
Frenkel S, Nir I, Hendler K, Lotem M, Eid A, Jurim O, et al. Long-term survival of uveal melanoma patients after surgery for liver metastases. Br J Ophthalmol. 2009;93:1042–6.
Corrêa ZM, Augsburger JJ. Independent prognostic significance of gene expression profile class and largest basal diameter of posterior uveal melanomas. Am J Ophthalmol. 2016;162:20–7.
Walter S, Chao D, Feuer W, Schiffman J, Chan D, Harbour J. Prognostic implications of tumor diameter in association with gene expression profile for uveal melanoma. JAMA Ophthalmol. 2016;134:734–40.
Acknowledgements
The authors wish to thank Bradley Londres, external biomedical editor, for his invaluable assistance in editing and improving this manuscript. This study was supported in part by a grant of the Spanish Ministry of Health, Instituto de Salud Carlos III, AES 2015 Proyectos de Salud-ISCIII (PI15/01461). The funding organization had no role in the design or conduct of this research.
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D. Lorenzo, None; J. M. Piulats, None; M. Ochoa, None; L. Arias, None; C. Gutiérrez, None; J. Català, None; E. Cobos, None; P. G. -Bru, None; B. Dias, None; N. P. -Pérez, None; J. M. Caminal, None.
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Corresponding author: Daniel Lorenzo
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Lorenzo, D., Piulats, J.M., Ochoa, M. et al. Clinical predictors of survival in metastatic uveal melanoma. Jpn J Ophthalmol 63, 197–209 (2019). https://doi.org/10.1007/s10384-019-00656-9
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DOI: https://doi.org/10.1007/s10384-019-00656-9