| Summary: | Abstract Background The mortality of nasopharyngeal carcinoma (NPC) is usually lower in females than in males, but the underlying mechanism remains largely unknown. We sought to describe the age-dependent patterns of gender disparities in NPC survival and explore the extent to which the confounder or mediation effects could explain these differences. Methods A total of 11,980 patients with NPC were reviewed. The effect of gender on cancer-specific survival (CSS) was assessed using Cox regression analyses. Two propensity score methods were conducted to control the confounding bias between genders. Restricted cubic spline regression was used to model the association of gender and age with mortality flexibly. Multiple mediation analysis was applied to estimate the direct or indirect effect of gender on CSS. Results Overall, 7026 males and 2320 females were analyzed. The crude CSS was significantly higher for females than males (10-year CSS 78.4% vs 70.3%; P < 0.001). Similar results were observed after adjusting for confounding bias. Gender disparities in NPC-specific mortality were age-dependent, where they would increase with age until peaking at age 55–60 years and decline rapidly afterward. Subgroup analyses revealed that females’ survival advantage was observed in the 18–45 age group and was more prominent in the 46–55 age group, but vanished in the > 55 age group. Either confounder or mediation effects only accounted for approximately 20% of the gender differences. Conclusions Gender disparities in cancer-specific mortality for patients with NPC were age-dependent. The differences mostly cannot be explained by confounder or mediation effects.
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