Background: The incidence of colorectal cancer (CRC) is increasing in the population under 50 years of age, with more than 10% of cases occurring in young adults. Fertility preservation counseling has therefore received increased attention in this younger patient population. The treatment of CRC is often based on multimodal therapies, including surgery, radiotherapy, chemotherapy, and, more recently, immunotherapy, which makes it difficult to estimate the expected effect of treatment on fertility. We, therefore, systematically analyzed the published literature on the gonadotoxic effects of CRC treatments to better advise patients on the risk of infertility and the need for fertility preservation measures. This systematic review and meta-analysis are part of the FertiTOX project, which aims to reduce the data gap regarding the gonadotoxicity of oncological therapies. Objectives: The aim of this review and meta-analysis is to evaluate the potential impact of CRC therapies on gonadal function to allow more accurate counseling regarding the risk of clinically relevant gonadotoxicity and the need for fertility preservation measures before oncological treatment. Materials and Methods: A systematic literature search was conducted in Medline, Embase, the Cochrane database of systematic reviews, and CENTRAL in March 2024. A total of 22 out of 4420 studies were included in the review. Outcomes were defined as clinically relevant gonadotoxicity, indicated by elevated follicle-stimulating hormone (FSH) and/or undetectable anti-Müllerian hormone (AMH) levels and/or the need for hormone replacement therapy in women and azoo-/oligozoospermia and/or low inhibin B levels in men. Studies with fewer than nine patients were excluded from the meta-analysis. Results: The qualitative analysis included 22 studies with 1634 subjects (775 women, 859 men). Treatment consisted of active surveillance after surgery (37.7%), chemotherapy (12.7%), radiation (0.2%), or radiochemotherapy (53.9%). In 0.5%, the therapy was not clearly described. The meta-analysis included ten studies and showed an overall prevalence of clinically relevant gonadotoxicity of 23% (95% CI: 13–37%). In women, the prevalence was 27% (95% CI: 11–54%), and in men, 18% (95% CI: 13–26%). A subanalysis by type of CRC was only possible for rectal cancer, with a prevalence of relevant gonadotoxicity of 39% (95% CI: 20–64%). In patients undergoing chemotherapy exclusively, the prevalence was 4% (95% CI: 2–10%). In those receiving only radiotherapy, the prevalence was 23% (95% CI: 10–44%); in contrast, it reached 68% (95% CI: 40–87%) in patients who received radiochemotherapy. Conclusions: This first meta-analysis of the clinically relevant gonadotoxicity of CRC therapies provides a basis for counseling on the risk of infertility and the need for fertility preservation measures. Despite the low prevalence of gonadotoxicity in cases receiving chemotherapy alone, fertility preservation is still recommended due to the uncertainty of subsequent therapy and the lack of large longitudinal data on individual treatment effects. Further prospective studies are needed to investigate the impact of CRC treatment on gonadal function and estimate the effect of new treatment modalities, such as immunotherapies.
背景：结直肠癌（CRC）在50岁以下人群中的发病率呈上升趋势，其中超过10%的病例发生于年轻成人群体。因此，针对这一年轻患者群体的生育力保护咨询日益受到重视。结直肠癌的治疗通常基于多模式疗法，包括手术、放疗、化疗以及近年兴起的免疫治疗，这使得评估治疗对生育力的预期影响变得困难。为此，我们系统分析了已发表的关于结直肠癌治疗性腺毒性效应的文献，以期为患者提供更精准的不孕风险咨询和生育力保护措施建议。本系统综述与荟萃分析是FertiTOX项目的一部分，该项目旨在缩小肿瘤治疗性腺毒性相关数据缺口。 目的：本综述与荟萃分析旨在评估结直肠癌治疗对性腺功能的潜在影响，从而为临床相关性腺毒性风险及肿瘤治疗前生育力保护措施的必要性提供更精准的咨询依据。 材料与方法：于2024年3月系统检索了Medline、Embase、Cochrane系统评价数据库及CENTRAL数据库。从4420项研究中最终纳入22项进行综述。结局指标定义为临床相关性腺毒性，具体表现为女性患者卵泡刺激素（FSH）水平升高和/或抗缪勒管激素（AMH）检测不到和/或需要激素替代治疗，男性患者出现无精子症/少精子症和/或抑制素B水平降低。荟萃分析排除了患者数少于9例的研究。 结果：定性分析共纳入22项研究，涉及1634名受试者（女性775人，男性859人）。治疗方式包括术后主动监测（37.7%）、化疗（12.7%）、放疗（0.2%）或放化疗（53.9%），0.5%的治疗方案描述不明确。荟萃分析纳入10项研究，显示临床相关性腺毒性的总体发生率为23%（95% CI：13–37%）。女性发生率为27%（95% CI：11–54%），男性为18%（95% CI：13–26%）。按结直肠癌类型进行的亚组分析仅针对直肠癌可行，其相关性腺毒性发生率为39%（95% CI：20–64%）。在仅接受化疗的患者中，发生率为4%（95% CI：2–10%）；仅接受放疗的患者中为23%（95% CI：10–44%）；而接受放化疗的患者中则高达68%（95% CI：40–87%）。 结论：这项首次针对结直肠癌治疗临床相关性腺毒性的荟萃分析，为不孕风险咨询和生育力保护措施必要性评估提供了依据。尽管单纯化疗患者的性腺毒性发生率较低，但由于后续治疗的不确定性以及缺乏个体化治疗效应的大规模纵向数据，仍建议进行生育力保护。未来需要进一步的前瞻性研究来探讨结直肠癌治疗对性腺功能的影响，并评估免疫治疗等新型治疗模式的效果。
肿瘤(癌症)患者之家