国际妇产科联盟IV期卵巢癌原发性与间隔性细胞减灭手术的生存结局：一项全国性人群基础的目标试验模拟研究

原发性细胞减灭手术与间隔性细胞减灭手术对国际妇产科联盟（FIGO）IV期卵巢癌患者预后的影响仍不确定，且可能因肿瘤分期和腹膜外转移位置而异。通过因果推断模拟目标试验，并结合倾向评分调整，已成为评估观察性数据中干预效果的主要方法。本研究旨在使用目标试验模拟，评估原发性与间隔性细胞减灭手术对IV期卵巢癌患者无进展生存期和总生存期的影响。我们利用法国全国医保数据库，模拟一项目标试验，探讨原发性与间隔性细胞减灭手术对IV期卵巢癌预后的因果影响（Surgery for Ovarian cancer FIGO 4: SOFI-4）。采用逆概率删失加权的克隆方法调整信息偏倚，并平衡两组基线特征。根据分期和腹膜外转移部位进行亚组分析。研究对象为2014年1月1日至2022年12月31日诊断为IV期卵巢癌、年龄未满75岁的健康患者。主要终点为5年无进展生存率，次要终点为7年总生存率。共纳入2772名患者，其中948人（34.2%）为IVA期，1824人（65.8%）为IVB期。原发性细胞减灭手术组有1182人（42.6%），间隔性手术组有1590人（57.4%）。原发性手术组的中位无进展生存期为19.7个月（四分位距19.3-20.1），而间隔手术组为15.7个月（四分位距15.7-16.1）。中位总生存期为63.1个月（四分位距61.7-65.4）与55.6个月（四分位距53.8-56.3）相比。结果显示，原发性细胞减灭手术在5年无进展生存率上增加了5.0个月（95%置信区间3.8-6.2），在7年总生存率上增加了3.9个月（95%置信区间1.9-6.2）。这一生存优势在IVA和IVB两个亚组中均有体现。原发性手术在伴有胸腔、膈上或腹外淋巴结转移的患者中也表现出改善的无进展和总生存期。本研究支持在适合的患者中考虑原发性细胞减灭手术优于间隔性手术，特别是对于存在腹膜外转移如膈上或腹外淋巴结的患者。

The effect of primary cytoreductive surgery vs interval cytoreductive surgery on International Federation of Gynecology and Obstetrics stage IV ovarian cancer outcomes remains uncertain and may vary depending on the stage and the location of extraperitoneal metastasis. Emulating target trials through causal assessment, combined with propensity score adjustment, has become a leading method for evaluating interventions using observational data.This study aimed to assess the effect of primary vs interval cytoreductive surgery on progression-free and overall survival in patients with International Federation of Gynecology and Obstetrics stage IV ovarian cancer using target trial emulation.Using the comprehensive French national health insurance database, we emulated a target trial to explore the causal impacts of primary vs interval cytoreductive surgery on stage IV ovarian cancer prognosis (Surgery for Ovarian cancer FIGO 4: SOFI-4). The clone method with inverse probability of censoring weighting was used to adjust for informative censoring and to balance baseline characteristics between the groups. Subgroup analyses were conducted based on the stages and extraperitoneal metastasis locations. The study included patients younger than 75 years of age, in good health condition, who were diagnosed with stage IV ovarian cancer between January 1, 2014, and December 31, 2022. The primary and secondary outcomes were respectively 5-year progression-free survival and 7-year overall survival.Among the 2772 patients included in the study, 948 (34.2%) were classified as having stage IVA ovarian cancer and 1824 (65.8%) were classified as having stage IVB ovarian cancer at inclusion. Primary cytoreductive surgery was performed for 1182 patients (42.6%), whereas interval cytoreductive surgery was conducted for 1590 patients (57.4%). The median progression-free survival for primary cytoreductive surgery was 19.7 months (interquartile range, 19.3-20.1) as opposed to 15.7 months (interquartile range, 15.7-16.1) for those who underwent interval cytoreductive surgery. The median overall survival was 63.1 months (interquartile range, 61.7-65.4) for primary cytoreductive surgery in comparison with 55.6 months (interquartile range, 53.8-56.3) for interval cytoreductive surgery. The findings of our study indicate that primary cytoreductive surgery is associated with a 5.0-month increase in the 5-year progression-free survival (95% confidence interval, 3.8-6.2) and a 3.9-month increase in 7-year overall survival (95% confidence interval, 1.9-6.2). These survival benefits of primary over interval cytoreductive surgery were observed in both the International Federation of Gynecology and Obstetrics stage IVA and IVB subgroups. Primary cytoreductive surgery demonstrated improved progression-free survival and overall survival in patients with pleural, supradiaphragmatic, or extra-abdominal lymph node metastasis.This study advocates for the benefits of primary cytoreductive surgery over interval cytoreductive surgery for patients with stage IV ovarian cancer and suggests that extraperitoneal metastases like supradiaphragmatic or extra-abdominal lymph nodes should not automatically preclude primary cytoreductive surgery consideration in suitable patients.