Superior Outcome of Women With Stage I/II Cutaneous Melanoma: Pooled Analysis of Four European Organisation for Research and Treatment of Cancer Phase III Trials

Abstract

Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.

Prognostic instrument for survival outcome in melanoma patients: based on data from the population-based Swedish Melanoma Register

“…Also after adjusting for tumour thickness, Clark's level of invasion and tumour ulceration, women had a 30% lower risk of CMM-related death than men. This superior non-stage effect for women has previously been found in studies with similar HR (19,20). Surprisingly, sex was not included in the final prognostic model in two of the largest published prognostic instruments based on AJCC data and from Queensland Australia respectively (3,4).…”

Clinicopathologic features associated with efficacy and long‐term survival in metastatic melanoma patients treated with BRAF or combined BRAF and MEK inhibitors

“…10,26,27 Several factors have been proposed to drive this (as reviewed by Sondak et al 28 ), but the influence of sex on survival in the metastatic setting is unclear. A single study conducted in the era before active systemic therapies showed that females had superior survival in comparison with males in a univariate analysis, but survival was similar in a multivariate analysis.…”

“…[6][7][8][9] The relative influence that these clinicopathologic factors and those known to be prognostic for early-stage melanoma (Breslow thickness of primary melanoma, ulceration, mitotic rate, and sex) 6,10 may have on MAPK inhibitor drug efficacy has not been studied formally in a multivariate model with adequate follow-up. Furthermore, longer term survival (>3 years) with MAPK inhibitors has not been reported, and there are limited data about the success of subsequent therapies in those progressing on MAPK inhibitors (particularly anti-programmed cell death 1 [PD-1] therapy).…”

Effect of biology on the outcome of female melanoma patients

“…The first hypothesis was controverted and the second hypothesis was advocated by the fact that the female survival advantage persisted even following adjustment for factors such as Breslow's thickness, and that lymph node and visceral organ metastases did not affect the higher survival rate of female patients (4,(5)(6)(7)(8)(9)(10)(11). Thus, it was concluded that the aggressiveness of the disease did not affect the survival benefit of female melanoma patients.…”

“…In order to explain this difference, researchers have suggested two major hypotheses so far: The first hypothesis is based on behavioral characteristics, such as that men have more advanced disease at diagnosis due to certain lifestyle characteristics (i.e., men are exposed to the sun more often and for longer periods compared with women, and are less conscious of skin care and skin cancer, thus not taking sufficient preventive measures) that may result in delays in screening, detection and diagnosis of the disease (4). The second hypothesis is that there is a biological trait that has yet to be elucidated, which accounts for the sex-related survival difference in melanoma; this unclear biological trait is believed to be associated with either the tumor per se (namely, the disease in female patients is naturally less aggressive), or with factors within the host (namely, female sex prevents disease progression and spread) (5)(6)(7)(8)(9).…”