The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark

Abstract

Background: Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking.

Methods: We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997-2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first.

Results: The median age at metastatic melanoma diagnosis was 64 years. Over 40% of patients died within one year of metastatic diagnosis and ~70% died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6% with cuSCC or basal cell carcinoma (BCC), 3.9% with actinic keratosis (AK), and 0.7% with Bowen's disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8% (42.5 per 1000 person-years [PY]); AK, 0.8% (18.6 per 1000 PY); cuSCC, 0.1% (1.7 per 1000 PY); Bowen's disease, 0.04% (0.8 per 1000 PY); and keratoacanthoma (KA), 0%. Non-cuSCC was observed in 3 patients (0.1%; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung.

Conclusion: CuSCC and non-cuSCC were rare events among metastatic melanoma patients.

Keywords: Actinic keratosis (AK); Basal-cell carcinoma (BCC); Bowen’s disease; Cutaneous melanoma; Cutaneous squamous-cell carcinoma (cuSCC); Danish Cancer Registry; Incidence; National Pathology Registry; Non-cutaneous squamous-cell carcinoma (non-cuSCC); Population-based; keratoacanthoma (KA).

Fig. 1

Kaplan Meier overall survival curve for metastatic melanoma patients post metastatic disease diagnoses. Figure Legend: Figure 1 shows the overall survival (in months) after onset of metastatic melanoma, presented for all patients, patients with Stage IV melanoma at initial diagnosis, and patients who had initial earlier stage melanoma then progressed to stage IV melanoma. The numbers of patients at risk at 0, 3, 6, 12, 36, and 60 months for each of these three groups are shown in the table immediately below the survival curves