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Association Between Adjuvant Therapy and Survival in Stage II–III Endometrial Cancer: Influence of Malignant Peritoneal Cytology



The aim of this study was to examine the survival effect of adjuvant therapy in stage II–III endometrial cancer based on peritoneal cytology results.


The National Cancer Institute’s Surveillance, Epidemiology, and End Results Program was retrospectively queried to examine 7467 women with stage II–III endometrial cancer who underwent hysterectomy, and with available peritoneal cytology results, from 2010 to 2016. A Cox proportional hazard regression model was fitted to assess the association between adjuvant therapy and all-cause mortality stratified by peritoneal cytology results.


Malignant peritoneal cytology was reported in 1662 (22.3%) women and was associated with non-endometrioid histology, higher tumor stage, and nodal metastasis (p < 0.05). In a propensity score-weighted model, malignant peritoneal cytology was associated with increased all-cause mortality compared with negative peritoneal cytology (hazard ratio 1.35, 95% confidence interval 1.23–1.48). Adjuvant therapy types varied based on histology and peritoneal cytology results. In non-endometrioid histology, the combination of chemotherapy and whole pelvic radiotherapy (WPRT) was associated with improved overall survival compared with chemotherapy or WPRT alone irrespective of the peritoneal cytology results (p < 0.05). The combination of chemotherapy and WPRT was also associated with improved overall survival in women with endometrioid histology and malignant peritoneal cytology (p = 0.026). Women with endometrioid histology and negative peritoneal cytology represented the most common subpopulation (46.5%), and overall survival was similar regardless of which of the three adjuvant therapy modalities was used (p = 0.319).


Malignant peritoneal cytology is prevalent and prognostic in stage II–III endometrial cancer. This study found that the surgeon’s choice and benefit of adjuvant therapy for women with stage II–III endometrial cancer differed depending on the status of peritoneal cytology.

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Data Availability

The data that support the findings of this study are openly available in the National Cancer Institute’s SEER program (


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Koji Matsuo has received funding support from Ensign Endowment for Gynecologic Cancer Research. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations



Koji Matsuo designed the study, initiated the collaborations, cleaned and analyzed the data, created the figures and tables, interpreted the results, and drafted and revised the manuscript with others. He is also the corresponding author of this study. David J. Nusbaum contributed to the analysis, interpreted the results, and revised the manuscript. Shinya Matsuzaki contributed to the literature overview and intellectual inputs, interpreted the results, and edited the manuscript. Lynda D. Roman and Jason D. Wright supervised the study and revised the manuscript. Philipp Harter reviewed the results and revised the manuscript. Maximilian Klar contributed to the study concept and design, instructed the analytic approach, interpreted the results, and revised the manuscript.

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Correspondence to Koji Matsuo MD, PhD.

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The following disclosures are declared, outside the submitted work: Jason D. Wright is a consultant for Clovis Oncology and has undertaken research funding for Merck. Lynda D. Roman is a consultant for Quantgene. Koji Matsuo has received honorarium from Chugai, textbook editorial expenses from Springer, and investigator meeting attendance expenses from VBL therapeutics. Shinya Matsuzaki has received research funding from MSD. Philipp Harter has received personal fees, non-financial support, honoraria for lectures, advisory board fees, and travel support from AstraZeneca and Roche; non-financial support and travel support from Medac; personal fees, honoraria for lectures, and advisory board fees from Tesaro and PharmaMar; personal fees and honoraria for advisory board participation from Clovis and Lilly; personal fees and honoraria for lectures from Stryker; and personal fees and honoraria for advisory board participation from Immunogen. Maximilian Klar has received advisory board fees from Tesaro and GSK. David J. Nusbaum has no conflicts of interest to declare.

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Matsuo, K., Matsuzaki, S., Nusbaum, D.J. et al. Association Between Adjuvant Therapy and Survival in Stage II–III Endometrial Cancer: Influence of Malignant Peritoneal Cytology. Ann Surg Oncol 28, 7591–7603 (2021).

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