Lee Cha Len, Martinez Erika, Malon Gimenez Diego, Muniz Thiago Pimentel, Butler Marcus Otho, Saibil Samuel David
Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON M5G 1Z5, Canada.
Cancers (Basel). 2025 Jan 13;17(2):238. doi: 10.3390/cancers17020238.
The incidence of melanoma among young adults has risen, yet mortality has declined annually since the introduction of immune checkpoint inhibitors (ICI). The utilization of peri-operative ICI has significantly altered the treatment landscape in melanoma, with PD-1 inhibitors showing promising efficacy in improving relapse-free survival rates in high-risk stage II-III disease. With the increasing use of ICI, secondary concerns have emerged regarding the impact of cancer drugs on fertility and reproductive health among women of childbearing potential, especially in early-stage cancer settings. The exclusion of pregnant women from trials contributes to limited human data and clinical uncertainties, such as maternal and fetal toxicities related to ICI exposure during pregnancy, as well as the value of fertility preservation before ICI therapy. Uncertainty persists regarding pregnancy post-adjuvant immunotherapy, given the potential detrimental effects of hormonal and immunological changes during pregnancy on melanoma relapse. There is additional uncertainty about whether pregnancy-associated melanoma (PAM) represents a distinct disease entity that warrants tailored management compared to non-pregnant cases. Our review aims to give an overview of oncofertility practices among female melanoma patients after immunotherapy. We also focus on the literature gap in the published evidence and synthesize summaries regarding ICI toxicities on reproductive health and fetal development, pregnancy planning, and recurrence risks after melanoma treatment.
年轻成年人中黑色素瘤的发病率有所上升,但自免疫检查点抑制剂(ICI)问世以来,死亡率每年都在下降。围手术期ICI的应用显著改变了黑色素瘤的治疗格局,PD-1抑制剂在提高高危II-III期疾病的无复发生存率方面显示出有前景的疗效。随着ICI使用的增加,对于有生育潜力的女性而言,癌症药物对生育能力和生殖健康的影响引发了更多关注,尤其是在早期癌症的情况下。将孕妇排除在试验之外导致人类数据有限以及临床存在不确定性,例如孕期接触ICI相关的母婴毒性,以及ICI治疗前生育力保存的价值。鉴于孕期激素和免疫变化对黑色素瘤复发的潜在不利影响,辅助免疫治疗后的妊娠情况仍存在不确定性。与非妊娠病例相比,妊娠相关性黑色素瘤(PAM)是否代表一种需要针对性管理的独特疾病实体也存在额外的不确定性。我们的综述旨在概述免疫治疗后女性黑色素瘤患者的肿瘤生育学实践。我们还关注已发表证据中的文献空白,并综合有关ICI对生殖健康和胎儿发育的毒性、妊娠计划以及黑色素瘤治疗后复发风险的总结。