Rewinding the clock on positive peritoneal cytology in endometrial cancer: does it predict prognosis in low-risk disease?

Objective: Positive peritoneal cytology in endometrial cancer is a known risk factor for worse oncologic outcomes but is not used for staging purposes or to guide adjuvant treatment. Additionally, its prognostic impact on low-risk patients remains unclear. Therefore, we investigated the role of positive peritoneal cytology in patients with endometrial cancer and focused on low-risk disease. Methods: This is a retrospective cohort study including all consecutive patients undergoing primary surgery for endometrial cancer at Mayo Clinic from 1999 to 2021. The role of positive peritoneal cytology was investigated in the entire cohort and in 2 subgroups: the National Comprehensive Cancer Network (NCCN) low-risk group, including low-risk patients according to NCCN guidelines (endometrioid, grade 1-2, stage IA) and the European Society of Gynecologic Oncology/European Society of Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) low-risk group, including low-risk patients according to ESGO/ESTRO/ESP guidelines (as NCCN, plus no lymphovascular space invasion). Univariate and multivariable analyses were used to evaluate the association of positive peritoneal cytology with recurrence within 5 years after surgery, and Kaplan-Meier survival analyses were performed in all groups. Results: A total of 3517 patients were included, 1911 in the NCCN low-risk group and 1832 in the ESGO/ESTRO/ESP low-risk group. Positive peritoneal cytology was found in 15.9% of the entire cohort (559/3517), 8.1% of the NCCN low-risk group (154/1911), and 7.9% of the ESGO/ESTRO/ESP low-risk group (145/1832). In both low-risk groups, 5-year recurrence-free survival was worse in patients with positive peritoneal cytology (p < .01 and p = .03, respectively), but there was no difference in overall survival. On univariate analysis, age, tumor grade, and positive peritoneal cytology were significant predictors of recurrence in both subgroups. After multivariable analysis, positive peritoneal cytology remained independently associated with recurrence (p < .01 and p = .03, respectively). Conclusions: Positive peritoneal cytology was an independent predictor of recurrence and was associated with worse recurrence-free survival in patients with low-risk endometrial cancer. However, overall survival was not impacted.