Time interval from biopsy of endometrial atypical hyperplasia to surgery and risk for concurrent endometrial carcinoma – A retrospective study

Approximately 40% of women diagnosed with endometrial atypical hyperplasia (EAH) on endometrial biopsy already have endometrial carcinoma (EC) at the time of hysterectomy.1 We aimed to study whether the time interval between EAH diagnosis and surgery is associated with an increased rate of a final diagnosis of EC. A single-centre, retrospective cohort study included all consecutive patients receiving surgical staging for EAH from June 2009 to June 2021. We included only cases in whom the preoperative endometrial biopsy pathological diagnosis of EAH was reviewed and confirmed by an expert gynaecological pathologist in the treating medical centre. The primary outcome of this study was EC diagnosis in post-surgical histology in relation to time from EAH biopsy to surgery (waiting time). Waiting time was defined as the number of days from the biopsy that showed EAH, until the date of surgery. Staging surgery included lymph node evaluation. The study was approved by the institutional review board (IRB number protocol #2020–1904) of the Jewish General Hospital, Montreal, Quebec, Canada. Overall, 160 patients were included. The median age of patients was 61 years (interquartile range [IQR] 53–69 days). The median waiting time was 106 days (mean 132, IQR 75–138 days). There were 60 patients (37.5%) with concurrent EC on the final histology. There was no difference in the waiting time between women with a final histology of EC compared with women without an EC (median 85 days, IQR 61–124 days versus 117 days, IQR 90–177 days, p = 0.09; Table 1). Among women with EC, there were 12/60 (20.0%) with above Stage IA disease and the remaining 48 (80%) with Stage IA disease. There was no difference in waiting time in women with stage IA and women more than stage IA disease (median 83 days, IQR 68–108 days versus 99 days, IQR 62–128 days, p = 0.62). Waiting time was similar in EC with (n = 3) versus without (n = 57) lymphovascular space invasion (p = 0.26) and in EC with (n = 48) or without (n = 12) myometrial invasion (p = 0.34). There was no difference in waiting time between patients with positive lymph nodes (n = 2) versus negative lymph nodes (n = 58) (p = 0.46) and between women requiring adjuvant therapy (n = 15) compared with those who did not (n = 45) (p = 0.74). The rate of preoperative progesterone treatment, mode of endometrial sampling and body mass index were similar in both groups (p = 0.22, p = 0.17 and p = 0.15, respectively). In this study, wait time for surgery for patents with a preoperative diagnosis of EAH was not associated with the final pathology of EC or with well-known prognostic characteristics of EC, such as lymphovascular space invasion and myometrial invasion. Although there are inconclusive data regarding the implication of waiting times for EC,2-4 we did not find literature regarding waiting times for patients with EAH. The median time to surgery in our study of 106 days is much higher than the mean time reported in studies for preoperative diagnosis of EC (with 56 days being a cutoff of worse prognosis3 and 42 days being approximately the 75th centile of waiting time4). The lack of correlation between waiting time and outcome in our study is therefore reassuring, as the reported waiting time in our cohort of EAH is relatively long. Our cohort of EAH patients may provide an unbiased cohort of patients who are judged by practitioners to be of the same baseline risk for worse prognosis or for harbouring EC. The main limitations of this study are its retrospective nature and the possibility of referral bias, and its relatively small sample size. Our data allow us to reassure patients that when surgery is delayed with a mean of 132 days there is no increased risk for a final diagnosis of EC. Gabriel Levin, Walter Gotlieb, and Emad Matanes: Conceptualization, formal analysis, investigation and methodology, writing – original draft, and writing – review and editing. Shannon Salvador and Susie Lau: Clinical data acquisition, investigation, drafting and revising. None. This study was supported by grants from the Israel Cancer Research Fund, the Gloria's Girls Fund, and the Susan and Jonathan Wener Fund. None declared. The data that support the findings of this study are available from the corresponding author upon reasonable request. The study was approved by the institutional review board (IRB number protocol #2020–1904) of the Jewish General Hospital, Montreal, Quebec, Canada.

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