Vol 72, No 5 (2022)
Guidelines / Expert consensus
Published online: 2022-10-19

open access

Page views 3757
Article views/downloads 332
Get Citation

Connect on Social Media

Connect on Social Media

Diagnostic and therapeutic management of patients with ocular melanomas – recommendations of the Polish Society of Oncology

Piotr Rutkowski1, Bożena Romanowska-Dixon2, Anna Markiewicz2, Krzysztof Zieniewicz3, Katarzyna Kozak1, Paweł Rogala1, Tomasz Świtaj1, Monika Dudzisz-Sledź1
Nowotwory. Journal of Oncology 2022;72(5):342-352.


Uveal melanoma is the most common malignant neoplasm of the eyeball, developing from melanocytes of the uveal membrane of the eye, which is significantly different from melanoma of the conjunctiva, mucous membranes and skin. The management of this disease is therefore different from that of other forms of melanoma. The disease is most often confined to the eye and its local treatment includes radiation therapy and surgery. Some patients, despite successful local treatment, develop distant metastases, most often located in the liver. The guidelines presented here cover the principles of diagnosis, prognostic evaluation and treatment of both the disease confined to the eyeball and the disease at the metastatic stage. The principles of management of conjunctival melanoma are also discussed. The recommen­dations are based on a review of the literature and expert opinion, and are accompanied by an assessment of their strength and reliability.

Article available in PDF format

View PDF Download PDF file


  1. Walewski J, Dziurda D, Bidziński M, et al. Consensus on methods of development of clinical practice guidelines in oncology under the auspices of Maria Sklodowska-Curie National Research Institute of Oncology and the Agency for Health Technology Assessment and Tariff System. Nowotwory. Journal of Oncology. 2022; 72(1): 44–50.
  2. Jager MJ, Shields CL, Cebulla CM, et al. Uveal melanoma. Nat Rev Dis Primers. 2020; 6(1): 24.
  3. Berus T, Halon A, Markiewicz A, et al. Clinical, Histopathological and Cytogenetic Prognosticators in Uveal Melanoma - A Comprehensive Review. Anticancer Res. 2017; 37(12): 6541–6549.
  4. Kaliki S, Shields CL. Uveal melanoma: relatively rare but deadly cancer. Eye (Lond). 2017; 31(2): 241–257.
  5. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011; 118(9): 1881–1885.
  6. Virgili G, Gatta G, Ciccolallo L, et al. EUROCARE Working Group, EUROCARE Working Group. Incidence of uveal melanoma in Europe. Ophthalmology. 2007; 114(12): 2309–2315.
  7. Rodrigues M, Koning Lde, Coupland SE, et al. UM Cure 2020 Consortium. So Close, yet so Far: Discrepancies between Uveal and Other Melanomas. A Position Paper from UM Cure 2020. Cancers (Basel). 2019; 11(7).
  8. Wojciechowska U, Didkowska J, Irmina M, et al. Nowotwory złośliwe w Polsce w 2018 roku. Krajowy Rejestr Nowotworów, Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie – Państwowy Instytut Badawczy. http://onkologia.org.pl/publikacje/.
  9. Kivelä T. The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death. Br J Ophthalmol. 2009; 93(9): 1129–1131.
  10. Shields CL, Kaliki S, Cohen MN, et al. Prognosis of uveal melanoma based on race in 8100 patients: The 2015 Doyne Lecture. Eye (Lond). 2015; 29(8): 1027–1035.
  11. Al-Jamal RT, Cassoux N, Desjardins L, et al. The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group. Ophthalmology. 2016; 123(4): 898–907.
  12. Kivelä T. Prevalence and epidemiology of ocular melanoma. In: Murray T, Boldt HC. ed. Ocular Melanoma: Advances in Diagnostic and Therapeutic Strategies. Future Science, London 2014: 21–38.
  13. Żygulska-Mach H. Epidemiologia czerniaka oka. Współczesna Onkologia. 1998; 8: 226–227.
  14. Cabanis EEA, Bourgeois H, Iba-Zizen MT. Imagerie en ophtalmologie. Masson, Paris 1996: 486–502.
  15. Shields CL, Furuta M, Thangappan A, et al. Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol. 2009; 127(8): 989–998.
  16. Folberg R, Rummelt V, Parys-Van Ginderdeuren R, et al. The prognostic value of tumor blood vessel morphology in primary uveal melanoma. Ophthalmology. 1993; 100(9): 1389–1398.
  17. Bronkhorst IHG, Jager MJ. Inflammation in uveal melanoma. Eye (Lond). 2013; 27(2): 217–223.
  18. Harbour JW, Onken MD, Roberson EDO, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010; 330(6009): 1410–1413.
  19. Romanowska-Dixon B, Jakubowska B, Karska-Basta I, et al. Uveal Tumors. Differential diagnosis of intraocular tumors. In: Romanowska-Dixon B, Jager MJ, Coupland S. ed. Ocular Oncology. PZWL Wydawnictwo Lekarskie, Warszawa 2020: 105–369.
  20. Shields JA, Shields CL. Management of posterior uveal melanoma: past, present, and future: the 2014 Charles L. Schepens lecture. Ophthalmology. 2015; 122(2): 414–428.
  21. Rantala ES, Hernberg M, Kivelä TT. Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Res. 2019; 29(6): 561–568.
  22. Amin MB, Greene F. AJCC Cancer Staging Manual. 8th ed. Springer International Publishing, Cham 2017.
  23. Dithmar S, Diaz CE, Grossniklaus HE. Intraocular melanoma spread to regional lymph nodes: report of two cases. Retina. 2000; 20(1): 76–79.
  24. Damato EM, Damato BE. Detection and time to treatment of uveal melanoma in the United Kingdom: an evaluation of 2,384 patients. Ophthalmology. 2012; 119(8): 1582–1589.
  25. Shields JA, Shields CL, Ehya H, et al. Fine-needle aspiration biopsy of suspected intraocular tumors. The 1992 Urwick Lecture. Ophthalmology. 1993; 100(11): 1677–1684.
  26. NCCN Guidelines. Uveal Melanoma. Version 3.2020.
  27. Shields JA, Mashayekhi A, Ra S, et al. Pseudomelanomas of the posterior uveal tract: the 2006 Taylor R. Smith Lecture. Retina. 2005; 25(6): 767–771.
  28. Shields CL, Dalvin LA, Ancona-Lezama D, et al. CHOROIDAL NEVUS IMAGING FEATURES IN 3,806 CASES AND RISK FACTORS FOR TRANSFORMATION INTO MELANOMA IN 2,355 CASES: The 2020 Taylor R. Smith and Victor T. Curtin Lecture. Retina. 2019; 39(10): 1840–1851.
  29. Shields CL, Shields JA, Cater J, et al. Plaque radiotherapy for uveal melanoma: long-term visual outcome in 1106 consecutive patients. Arch Ophthalmol. 2000; 118(9): 1219–1228.
  30. Melia BM, Abramson DH, Albert DM, et al. Collaborative Ocular Melanoma Study Group. Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16. Ophthalmology. 2001; 108(2): 348–366.
  31. Collaborative Ocular Melanoma Study Group. 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(12): 1684–1693.
  32. Simpson E, Gallie B, Laperrierre N, et al. The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma. Brachytherapy. 2014; 13(1): 1–14.
  33. Straatsma BR. Golden Jubilee Lecture. Randomised clinical trials of choroidal melanoma treatment. Indian J Ophthalmol. 2003; 51(1): 17–23.
  34. Diener-West M, Earle JD, Fine SL, et al. Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18. Arch Ophthalmol. 2001; 119(7): 969–982.
  35. Mortality in patients with small choroidal melanoma. COMS report no. 4. The Collaborative Ocular Melanoma Study Group. Arch Ophthalmol. 1997; 115(7): 886–893.
  36. Gragoudas ES, Lane AM, Munzenrider J. Long-term risk of local failure after proton therapy for choroidal/ciliary body melanoma. Trans Am Ophthalmol Soc. 2002; 100: 43–48; discussion 48-49.
  37. Damato B. The role of eyewall resection in uveal melanoma management. Int Ophthalmol Clin. 2006; 46(1): 81–93.
  38. Konstantinidis L, Groenewald C, Coupland SE, et al. Long-term outcome of primary endoresection of choroidal melanoma. Br J Ophthalmol. 2014; 98(1): 82–85.
  39. Kubicka-Trząska A, Morawski K, Markiewicz A, et al. Prevention and treatment of the toxic tumour syndrome following primary proton beam therapy of choroidal melanomas. Archives of Medical Science - Civilization Diseases. 2020; 5(1): 22–28.
  40. Turkoglu EB, Pointdujour-Lim R, Mashayekhi A, et al. PHOTODYNAMIC THERAPY AS PRIMARY TREATMENT FOR SMALL CHOROIDAL MELANOMA. Retina. 2019; 39(7): 1319–1325.
  41. Rundle P. Treatment of posterior uveal melanoma with multi-dose photodynamic therapy. Br J Ophthalmol. 2014; 98(4): 494–497.
  42. Grossniklaus HE. Progression of ocular melanoma metastasis to the liver: the 2012 Zimmerman lecture. JAMA Ophthalmol. 2013; 131(4): 462–469.
  43. Grossniklaus HE. Understanding Uveal Melanoma Metastasis to the Liver: The Zimmerman Effect and the Zimmerman Hypothesis. Ophthalmology. 2019; 126(4): 483–487.
  44. Rowcroft A, Loveday BPT, Thomson BNJ, et al. Systematic review of liver directed therapy for uveal melanoma hepatic metastases. HPB (Oxford). 2020; 22(4): 497–505.
  45. Fiorentini G, Aliberti C, Del Conte A, et al. Intra-arterial hepatic chemoembolization (TACE) of liver metastases from ocular melanoma with slow-release irinotecan-eluting beads. Early results of a phase II clinical study. In Vivo. 2009; 23(1): 131–137.
  46. Pelster MS, Gruschkus SK, Bassett R, et al. Nivolumab and Ipilimumab in Metastatic Uveal Melanoma: Results From a Single-Arm Phase II Study. J Clin Oncol. 2021; 39(6): 599–607.
  47. Piulats JM, Espinosa E, de la Cruz Merino L, et al. Nivolumab Plus Ipilimumab for Treatment-Naïve Metastatic Uveal Melanoma: An Open-Label, Multicenter, Phase II Trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402). J Clin Oncol. 2021; 39(6): 586–598.
  48. Rodriguez-Vidal C, Fernandez-Diaz D, Fernandez-Marta B, et al. Treatment of Metastatic Uveal Melanoma: Systematic Review. Cancers (Basel). 2020; 12(9).
  49. Sacco JJ, Carvajal R, Butler MO, et al. 64MO A phase (ph) II, multi-center study of the safety and efficacy of tebentafusp (tebe) (IMCgp100) in patients (pts) with metastatic uveal melanoma (mUM). Ann Oncol. 2020; 31: S1442–S1443.
  50. Nathan P, Hassel JC, Rutkowski P, et al. IMCgp100-202 Investigators. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021; 385(13): 1196–1206.
  51. Shields JA, Shields CL. Intraocular Tumors: An Atlas and Textbook 3rd ed. Wolters Kluwer 2015.
  52. Barker CA, Salama AK. New NCCN Guidelines for Uveal Melanoma and Treatment of Recurrent or Progressive Distant Metastatic Melanoma. J Natl Compr Canc Netw. 2018; 16(5S): 646–650.
  53. D’Amato B. Vasculopathy After Treatment of Choroidal Melanoma. In: Joussen AM, Gardner TW, Kirchhof B, Ryan S. ed. Retinal Vascular Disease. Springer 2007: 582–591.
  54. Finger PT, Chin KJ, Semenova EA, et al. Anti-vascular endothelial growth factor bevacizumab (avastin) for radiation retinopathy. Arch Ophthalmol. 2007; 125(6): 751–756.
  55. Nathan P, Cohen V, Coupland S, et al. United Kingdom Uveal Melanoma Guideline Development Working Group. Uveal Melanoma UK National Guidelines. Eur J Cancer. 2015; 51(16): 2404–2412.
  56. Blum ES, Yang J, Komatsubara KM, et al. Clinical Management of Uveal and Conjunctival Melanoma. Oncology (Williston Park). 2016; 30(1): 29–32, 34.
  57. McLaughlin CC, Wu XC, Jemal A, et al. Incidence of noncutaneous melanomas in the U.S. Cancer. 2005; 103(5): 1000–1007.
  58. Shields CL, Markowitz JS, Belinsky I, et al. Conjunctival melanoma: outcomes based on tumor origin in 382 consecutive cases . Ophthalmology. 2011; 118(2): 389-95.e1–2.
  59. Missotten GS, Keijser S, De Keizer RJW, et al. Conjunctival melanoma in the Netherlands: a nationwide study. Invest Ophthalmol Vis Sci. 2005; 46(1): 75–82.
  60. Shields CL, Shields JA, Gündüz K, et al. Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients. Arch Ophthalmol. 2000; 118(11): 1497–1507.
  61. Wong JR, Nanji AA, Galor A, et al. Management of conjunctival malignant melanoma: a review and update. Expert Rev Ophthalmol. 2014; 9(3): 185–204.
  62. Paridaens AD, McCartney AC, Minassian DC, et al. Orbital exenteration in 95 cases of primary conjunctival malignant melanoma. Br J Ophthalmol. 1994; 78(7): 520–528.
  63. Norregaard JC, Gerner N, Jensen OA, et al. Malignant melanoma of the conjunctiva: occurrence and survival following surgery and radiotherapy in a Danish population. Graefes Arch Clin Exp Ophthalmol. 1996; 234(9): 569–572.
  64. Finger PT, Czechonska G, Liarikos S. Topical mitomycin C chemotherapy for conjunctival melanoma and PAM with atypia. Br J Ophthalmol. 1998; 82(5): 476–479.
  65. Kurli M, Finger PT. Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia: 12 years' experience. Graefes Arch Clin Exp Ophthalmol. 2005; 243(11): 1108–1114.
  66. Demirci H, McCormick SA, Finger PT. Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia: clinical experience with histopathologic observations. Arch Ophthalmol. 2000; 118(7): 885–891.
  67. Ditta LC, Shildkrot Y, Wilson MW. Outcomes in 15 patients with conjunctival melanoma treated with adjuvant topical mitomycin C: complications and recurrences. Ophthalmology. 2011; 118(9): 1754–1759.
  68. Russell HC, Chadha V, Lockington D, et al. Topical mitomycin C chemotherapy in the management of ocular surface neoplasia: a 10-year review of treatment outcomes and complications. Br J Ophthalmol. 2010; 94(10): 1316–1321.
  69. Khong JJ, Muecke J. Complications of mitomycin C therapy in 100 eyes with ocular surface neoplasia. Br J Ophthalmol. 2006; 90(7): 819–822.
  70. Finger PT, Sedeek RW, Chin KJ. Topical interferon alfa in the treatment of conjunctival melanoma and primary acquired melanosis complex. Am J Ophthalmol. 2008; 145(1): 124–129.
  71. Herold TR, Hintschich C. Interferon alpha for the treatment of melanocytic conjunctival lesions. Graefes Arch Clin Exp Ophthalmol. 2010; 248(1): 111–115.
  72. Esmaeli B. Patterns of regional and distant metastasis in patients with conjunctival melanoma Experience at a cancer center over four decades. Ophthalmology. 2001; 108(11): 2101–2105.
  73. Tuomaala S, Kivelä T. Metastatic pattern and survival in disseminated conjunctival melanoma: implications for sentinel lymph node biopsy. Ophthalmology. 2004; 111(4): 816–821.

Nowotwory. Journal of Oncology