Survival outcomes of primary vs interval cytoreductive surgery for International Federation of Gynecology and Obstetrics stage IV ovarian cancer: a nationwide population-based target trial emulation

Floriane Jochum; Élise Dumas; Paul Gougis; Anne-Sophie Hamy; Denis Querleu; Lise Lecointre; Thomas Gaillard; Fabien Reyal; Fabrice Lecuru; Enora Laas; Cherif Akladios

doi:10.1016/j.ajog.2024.07.044

Survival outcomes of primary vs interval cytoreductive surgery for International Federation of Gynecology and Obstetrics stage IV ovarian cancer: a nationwide population-based target trial emulation

Am J Obstet Gynecol. 2024 Aug 5:S0002-9378(24)00818-4. doi: 10.1016/j.ajog.2024.07.044. Online ahead of print.

Authors

Affiliations

¹ Residual Tumor & Response to Treatment Laboratory, Translational Research Department, INSERM, U932 Immunity and Cancer, Paris, France; Department of Gynaecology, Strasbourg University Hospital, Strasbourg, France. Electronic address: jochum.floriane@gmail.com.
² Residual Tumor & Response to Treatment Laboratory, Translational Research Department, INSERM, U932 Immunity and Cancer, Paris, France; Department of Mathematics, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
³ Residual Tumor & Response to Treatment Laboratory, Translational Research Department, INSERM, U932 Immunity and Cancer, Paris, France; Department of Medical Oncology, Pitié-Salpêtrière Hospital, Sorbonne Université, Paris, France; Clinical Investigation Center (CIC-1901) INSERM, Department of Pharmacology, Pitié-Salpêtrière Hospital, Sorbonne Université, Paris, France.
⁴ Residual Tumor & Response to Treatment Laboratory, Translational Research Department, INSERM, U932 Immunity and Cancer, Paris, France; Department of Medical Oncology, Institut Curie, Paris, France.
⁵ UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
⁶ Department of Gynaecology, Strasbourg University Hospital, Strasbourg, France.
⁷ Department of Breast and Gynaecological Surgery, Institut Curie, Paris, France.
⁸ Residual Tumor & Response to Treatment Laboratory, Translational Research Department, INSERM, U932 Immunity and Cancer, Paris, France; Department of Breast and Gynaecological Surgery, Institut Curie, Paris, France.

PMID: 39111517
DOI: 10.1016/j.ajog.2024.07.044

Abstract

Background: 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.

Objective: 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.

Study design: 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.

Results: 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.

Conclusion: 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.

Keywords: FIGO stage IV; extraperitoneal metastases; interval cytoreductive surgery; ovarian cancer; overall survival; primary cytoreductive surgery; progression-free survival; target trial emulation.