Fertility Concerns and Outcomes Among Adolescent and Young Adult Males With Melanoma Receiving Immunotherapy: A Mixed-Methods Study

Abstract

Introduction: Immune checkpoint inhibitors (ICIs) are often the initial treatment choice for melanoma, the third most common cancer in the adolescent and young adult (AYA) male population. Although ICIs have improved survival rates, their effects on male fertility and the adequacy of related counseling remain unclear. This study aimed to both characterize the current state of fertility discussions in male AYA patients with melanoma receiving first-line ICIs and to explore their experiences and concerns regarding reproductive health.

Methods: We conducted a mixed-methods study of 38 male patients aged 18-39 with metastatic or locally advanced melanoma treated with first-line PD-1/PD-L1/CTLA-4 therapies at a single academic center between 2013 and 2024. Quantitative medical record review assessed fertility counseling and preservation actions. Semi-structured interviews were conducted with ten living patients from this cohort to explore knowledge, concerns, and experiences surrounding fertility and reproductive health. Thematic analysis identified key patient perspectives.

Results: Among 38 patients (median age 32), 71% had stage IV disease and received combination immunotherapy. 74% of patients experienced at least one immune-related adverse event (irAE). Fertility counseling was documented for 27 patients, with eight referred for fertility preservation. Of the ten interviewees, nine recalled discussing fertility, while only three pursued preservation. Qualitative themes included challenges accepting uncertainty about family planning, pressure to accelerate planning, feelings of forced maturity, difficulty processing complex information, and concerns about the reliability of information from family, providers, and social media.

Conclusion: Although most young males with advanced melanoma treated with first-line ICIs had documented fertility discussions, few elected fertility preservation. Patient experiences highlight the need for collaboration among oncologists, fertility specialists, and supportive professionals to develop tailored counseling and educational materials for male AYA patients with advanced melanoma.