Poorer survival outcomes in patients with multiple versus single primary melanoma

Abstract

Background: Given equivocal results related to overall survival (OS) for patients with multiple primary melanomas (MPMs) compared with those with single primary melanomas (SPMs) in previous reports, the authors sought to determine whether OS differs between these 2 cohorts in their center using their UPCI-96-99 database. Secondary aims were to assess the differences in recurrence-free survival (RFS). In a subset of patients, transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) was performed to assess disease-associated genes of interest.

Methods: This retrospective case-controlled study included patients with MPMs and age-, sex-, and stage-matched controls with SPMs at a 1:1 ratio. Cox regression models were used to evaluate the effect of the presence of MPMs on death and recurrence. NanoString PanCancer Immune Profiling was used to assess peripheral blood immune status in patients.

Results: In total, 320 patients were evaluated. The mean patient age was 47 years; 43.8% were male. Patients with MPMs had worse RFS and OS (P = .023 and P = .0019, respectively). The presence of MPMs was associated with an increased risk of death (hazard ratio [HR], 4.52, P = .0006), and increased risk of disease recurrence (HR, 2.17; P = .004) after adjusting for age, sex, and stage. The degree of tumor-infiltrating lymphocytes (TILs) was different between the first melanoma of MPMs and SPMs. Expression of CXCL6 and FOXJ1 was increased in PBMCs isolated from patients with MPMs.

Conclusions: Patients with MPMs had worse RFS and OS compared with patients with SPMs. Immunologic differences were also observed, including TIL content and expression of CXCL6/FOXJ1 in PBMCs of patients with MPMs, which warrant further investigation.

Keywords: immune profile; melanoma; multiple primary; survival; tumor-infiltrating lymphocytes.

FIGURE 1.

(A) Kaplan-Meier curves showing RFS in patients with multiple versus single primary melanomas excluding patients with MIS. The patients with MPM had worse RFS (log-r ank test P = .0038). (B) Kaplan-M eier curves showing (S) in patients with multiple versus single primary melanomas excluding patients with melanoma in situ. The patients with MPMs had worse OS (log-r ank test P = .00023). MIS indicates melanoma in situ; MPMs, multiple primary melanomas; OS, overall survival; RFS, recurrence-f ree survival; SPM, single primary melanoma.

FIGURE 2.

(A) Kaplan-Meier curves showing RFS in patients with multiple versus single primary melanomas excluding patients with melanoma in situ and stratifying by age. The patients with MPMs and ≥50 years old had worse RFS (log-rank test P = .0016). (B) Kaplan-Meier curves showing RFS in patients with multiple versus single primary melanomas excluding patients with melanoma in situ and stratifying by sex. The male patients with MPM had worse RFS (log-r ank test P < .0001). MIS indicates melanoma in situ; MPMs, multiple primary melanomas; RFS, recurrence-free survival; SPMs, single primary melanomas.

FIGURE 3.

(A) Kaplan-M eier curves showing RFS in patients with multiple versus single primary melanomas. The patients with MPM had worse RFS (log-r ank test P = .023). (B) Kaplan-M eier curves showing OS in patients with multiple versus single primary melanomas. The patients with MPM had worse OS (log-rank test P = .0019). MPMs indicate multiple primary melanomas; OS, overall survival; RFS, recurrence-free survival; SPM, single primary melanoma.

FIGURE 4.

(A,B) Receiver operating characteristic curve for CXCL6 and FOXJ1 as predictive biomarkers in the setting of multiple primary melanomas (MPMs). For CXCL6, the area under the curve was 0.72 with sensitivity and specificity of 0.93 and 0.57 respectively, for prediction of MPMs. For FOXJ1 area under the curve was 0.81 with sensitivity and specificity of 0.83 and 0.71, respectively. MPMs indicate multiple primary melanomas.