Sex differences in survival of cutaneous melanoma are age dependent

Abstract

This study identified sex differences in clinical presentation and survival for primary cutaneous melanoma without clinical evidence of metastasis at diagnosis from 1976 to 2008 in southern Germany. Melanoma-specific survival curves and estimated survival probabilities were generated using the Kaplan-Meier method. Multivariate survival analyses were carried out using the Cox modeling. Male patients had significantly thicker and more frequently ulcerated tumors and a lower 10-year disease-specific survival (DSS) and recurrence-free survival probability compared with females among patients of 43 years old or younger (DSS: 86.1 vs. 93.2%, P<0.001) and 44-60 years old (DSS: 83.5 vs. 90.1%, P<0.001). The survival advantage of female patients in terms of 10-year DSS and 10-year recurrence-free survival was not observed after an age of 60 years (P=0.21 and 0.51, respectively). Sex was of prognostic importance for DSS and survival after recurrence [hazards ratio (HR): 1.3; 95% confidence interval (CI): 1.1-1.6; P=0.002 and HR: 1.2; 95% CI: 1.0-1.5; P=0.018, respectively]. Stratified by age groups, sex remained of prognostic importance for DSS only in patients of 43 years or younger, and 44-60 years old (HR: 1.5; 95% CI: 1.0-2.1; P=0.03 and HR: 1.4; 95% CI: 1.1-2.0; P=0.02, respectively). Sex is an independent prognostic factor in surviving melanoma. The sex difference in survival with a better outcome for women is confined to melanoma patients of 60 years and younger. In addition, in younger age groups, male patients present with prognostically unfavorable features of primary melanoma. A female survival advantage is also known for other solid tumors such as colon and lung cancer; however, age dependency has not been studied.

Effect of biology on the outcome of female melanoma patients

“…Ulceration and increased thickness have already been identified as the most powerful tumor-related poor prognostic predictors (10,12). Similarly, the present study also observed that men had thicker and ulcerated lesions and that they had tumors located more often on the trunk, compared with women, in whom the tumors were more often located in the extremities.…”

“…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.…”

Sex Differences in Melanoma Survival are Not Related to Mitotic Rate of the Primary Tumor

“…In some previous studies, the female advantage disappeared at postmenopausal ages. 5,6,19,20 However, the majority of studies found that the female survival advantage persisted in these older groups, even among stage III and IV melanoma. [1][2][3][4][21][22][23][24][25][26] Therefore, combining our results and these previous studies, we conclude that females have a survival advantage in both premenopausal and postmenopausal age.…”

“…[1][2][3] The main arguments for rejecting these explanations were the persistence of the female advantage after adjustment for prognostic indicators presumably related to behavioral aspects (e.g., Breslow thickness and primary tumor location) and the persistence of the female advantage when melanoma metastasized to lymph nodes and distant organs. [1][2][3][4][5][6] Therefore, it is more likely that the female survival advantage is caused by some biological difference, which might be either tumor-related (e.g., males have more aggressive melanomas) or host-related (i.e., females are better able to resist progression and metastasis).…”

Neuro-endocrine-immune Crosstalk and Implications for Cancer Therapy

“…While still incompletely elucidated, understanding of the precise cellular and molecular mechanisms by which hormones alter these various immune functions is likely to play a crucial role in understanding gender differences in response not only to autoimmune diseases, but also chronic inflammatory conditions, human immunodeficiency virus (HIV) infection, cancer, bone marrow transplantation, or graft-versus-host disease (GVHD). For instance, gender has been shown to be an important and independent predictor of clinical outcome and survival in cutaneous melanoma, with premenopausal females (but not women older than 60 years) experiencing an improved prognosis [72,73]. The presence of sex steroid receptors in hematopoietic elements [24,58,66], as well as thymic and BM stromal cells [74][75][76] suggests that they may have a direct or indirect effect on immunity and hematopoiesis.…”