Image: PD 

1.  Patients diagnosed with stage III or IV melanoma are at risk for the development of further primary melanomas, particularly if they have a history of multiple primary melanomas prior to their diagnosis. 

Evidence rating level: 2 (Good)

Study Rundown: In recent year, B-raf inhibitors such as Vemurafenib have been approved for the management of metastatic melanoma. However, clinical trials of these drugs have shown evidence for possible carcinogenesis or increased tumor progression, such as atypical melanocytic proliferations and new primary melanomas. In order to better understand the effect of these drugs, the authors of this retrospective cohort study examined the background incidence of new primary melanomas in patients diagnosed with late stage melanoma.

After analyzing a total of 7778 patients diagnosed with stage III or IV melanoma, the authors found that they remained at risk for the development of additional primary melanomas. Risk factors included male sex and a history of multiple primary melanomas. The authors also compared these patients to those receiving BRAF inhibitors and found that incidence rates were higher in the latter group.

These results benefit from the cohort design and large study population. However, there are also several limitations on the interpretation of these results. First, this was a retrospective trial. Furthermore, comparing the outcomes from this population with patients receiving BRAF inhibitors involves possible measurement bias, as dermatologic assessment is more frequent in BRAF inhibitor trials.

Click to read the article in JCO

Relevant reading: Increased risk of second primary cancers after a diagnosis of melanoma

In-Depth [retrospective cohort study]: The authors of this study analyzed patients diagnosed with stage III or IV melanoma at Melanoma Institute Australia between 1983 and 2008. Patients who received a BRAF inhibitor were excluded. A total of 4215 patients with stage III and 3563 patients with stage IV were included in the study. The primary outcomes measured were 3 month, 6 month, 1 year and 10 year cumulative incidence of new primary melanoma (NPM) following diagnosis of the stage III or IV disease.

For the stage III patients, the 6 month, 1 year and 10 year cumulative incidence rates of developing an NPM were 1.2% (95% CI, 0.86-1.51), 1.8% (95% CI, 1.44-2.26) and 5.9% (95% CI, 5.08-6.74). For stage IV patients, the 3 month, 6 month and 1 year cumulative incidence rates were 0.2% (95% CI, 0.07-0.36), 0.3% (95% CI, 0.15-0.51) and 0.4% (95% CI, 0.25-0.7). For both populations, male sex and prior history of multiple primary melanomas increased the overall incidence of NPM.

By Monica Parks and Andrew Bishara

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