Immunotherapy levels survival differences between men and women with metastatic melanoma

Immunotherapy appears to erase long-standing survival differences between men and women with metastatic melanoma, according to a large national database study led by investigators at Saint John’s Cancer Institute in Santa Monica, California. The research was published in January 2026 in The American Journal of Surgery.

Skin cancer remains the most common cancer in the United States, with more than 9,500 people diagnosed every day. Updated estimates released by the Skin Cancer Foundation in January show melanoma diagnoses continuing to climb in the United States, even as newer therapies continue to reduce deaths from advanced disease. Overall melanoma diagnoses are expected to rise 10.6% in 2026.

Sex and age have long been recognized as prognostic factors in melanoma, with older men having worse outcomes. Prior research has linked older age to poorer survival, more advanced disease at diagnosis, and potential changes in immune function. Although immune checkpoint inhibitors have transformed treatment for advanced disease, whether these therapies alter historical survival patterns by sex and age has remained uncertain.

To examine this question, investigators led by Hilary R. Keller, M.D., a surgical oncology fellow at Saint John’s Cancer Institute in Santa Monica, Calif., analyzed data from the National Cancer Database, identifying 20,023 adults diagnosed with stage IV melanoma between 2012 and 2019. Overall, 67.7% of patients were men, and 44.2% received immunotherapy as part of their planned first course of treatment. Patients were stratified by sex and age, using age groups of 18 to 44 years, 45 to 60 years, and older than 60 years.

Among patients who did not receive immunotherapy, women consistently demonstrated better survival than men across all age groups. At 36 months, younger women had substantially higher overall survival than younger men, with smaller but still statistically significant differences observed among middle-aged and older cohorts.

That survival advantage was no longer evident once immunotherapy was introduced. Among patients receiving first-line immunotherapy, survival outcomes were similar between men and women across all age groups, a finding that persisted after multivariable adjustment.

“Survival was not significantly different between male and female patients with stage IV melanoma who received first course immunotherapy, regardless of age group,” Keller and colleagues wrote in their report.

Age, however, remained an important modifier of treatment benefit. Compared with patients ages 18 to 44 years, those ages 45 to 60 years and those older than 60 experienced significantly greater survival benefit from immunotherapy. This association did not differ between men and women.

The authors note that prior studies have shown sex-based differences in immune response that may contribute to survival advantages in women with metastatic melanoma who do not receive immunotherapy, while emphasizing that the mechanisms underlying these findings remain unclear.

“Further studies assessing the age disparities in patients receiving immunotherapy and increasing access to immunotherapy should be advocated,” they wrote.