Therapeutic Options in Metastatic Uveal Melanoma

Abstract

Systemic treatments for metastatic uveal melanoma patients give poor results. R0 resection of liver metastases showed a real benefit in survival in a very highly selected population. Based on our multivariate analysis, we propose surgical treatment to metastatic patients with time from diagnosis of uveal melanoma to liver metastases > 24 months, number of liver metastases ≤4 lesions, and absence of detectable miliary disease. Liver MRI is currently the best imaging method in this context even if miliary disease is still difficult to diagnose. Molecular and chromosomal classification strongly predicting metastatic death has to be used to identify genetic profiles and pathways involved in the pathogenesis of uveal melanoma leading to new targeted therapeutic strategies.

Molecular pathology of uveal melanoma

“…8,[152][153][154] It is, however, worth mentioning the potential targets for UM therapy, which have been revealed by efforts Update in the molecular pathology of uveal melanoma SE Coupland et al unravelling key signalling cascades implicated in the development and progression of UM. These include the inhibitors of the: MAPK/MEK signalling pathway; PI3K/AKT pathway at the level of AKT; mTOR; mTOR blockade combined with an IGF-1R antibody; tyrosine kinases; c-Met pathway; CXCR4 and histone deacetylase.…”

Molecular Pathology of Uveal Melanoma

“…Despite this, almost 50% of patients with UM will develop disseminated disease, predominantly in the liver, but also in the lungs (24% of patients) and bone (16%). 6 Early surgical removal of metastases has improved patient survival in some cases; 7,8 however, in general, the prognosis of UM patients with metastatic disease is currently poor because of the lack of effective chemotherapeutic agents.…”

Detection rate and prognostic value of circulating tumor cells and circulating tumor DNA in metastatic uveal melanoma

“…Patient characteristics and outcome were prospectively collected. CTCs (1) were detected in 12 of the 40 included patients (30%, range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Among the 26 patients with known detectable mutations, ctDNA was detected and quantified in 22 (84%, range 4-11,421 copies=mL).…”

“…Despite improvement of diagnosis and treatment of the primary eye tumor, there is no effective treatment of metastatic disease; the prognosis of patients with metastatic uveal melanoma is limited, and although a few patients experience extended survival, the median overall survival (OS) following metastases detection is less than 1 year. 6 Circulating tumor cells (CTCs), which are cancer cells detected in patient blood, may correspond to cancer "seeds" that initiate metastatic relapse. 7 Over the past two decades, both molecular and cytological detection techniques have been developed to detect these rare CTCs, either in blood (CTCs) and=or in bone marrow (disseminated tumor cells, DTCs).…”