The role of ulceration and stage as predictive factors of interferon efficacy in melanoma

The aim of this analysis was to determine the prognostic factors that can lead to the best results of Interferon treatment (as IFN or PEG-IFN) on patients with high-risk melanoma. The results indicate that tumor stage and ulceration were predictive factors for the efficacy of IFN/PEG-IFN therapy.

Malignant melanoma is a cancerous tumor of the cells that produce the dark pigment that gives color to the skin. Adjuvant (after surgery) Interferon has modest activity in patients at high risk for relapse. However, proper patient selection seems to influence the effects of Interferon.

2644 patients with high risk melanoma were involved in two studies. The first one was called EORTC 18991 with 1256 patients with stage III melanoma (spread to nearby areas or lymph nodes). They were given either PEG-IFN or observation after surgery. The second study was EORTC 18952 and involved 1388 patients with stage II b (tumor with a thickness between 2 to 4 mm or over 4 mm without spread to the lymph nodes) or stage III melanoma. Patients received either IFN or observation after surgery.

The results showed that 32% of patients had ulcerated (break in the skin) melanoma. The comparison between IFN or PEG-IFN and observation illustrated that the major effects were on relapse free survival (RFS – time without a relapse) but not on overall survival. Stage and the presence of ulceration were strong prognostic factors for RFS.  No significant differences were observed between Interferon and observation in patients without ulceration whatever the stage was. RFS was most improved in patients with stage II B/III and ulceration.

In conclusion these two studies demonstrated that stage and ulceration are strong prognostic factors. Also, they are predictive for the efficacy of IFN/PEG-IFN therapy in high risk patients with melanoma. The best results with Interferon were seen in patients with stage IIB or III melanoma. Ulcerated primary tumors responded better to Interferon than non-ulcerated ones.

Interferon treatment is associated with important side-effects, therefore it is necessary to identify which patients will indeed benefit from this treatment.