Rethinking Endometrial Thickness Thresholds that Prompt Endometrial Biopsy to Rule Out Endometrial Cancer

By Alexandra Morell, MD

Adjunct Instructor, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY

SYNOPSIS: In a retrospective review of 1,494 pre- and postmenopausal Black individuals who underwent transvaginal ultrasonography, 24 of 210 individuals (11.4%) with endometrial cancer had an endometrial thickness lower than the threshold for undergoing biopsy to detect cancer.

SOURCE: Doll KM, Pike M, Alson J, et al. Endometrial thickness as diagnostic triage for endometrial cancer among Black individuals. JAMA Oncol 2024;10:1068-1076.

Each year, approximately 65,000 women in the United States are diagnosed with endometrial cancer, representing the most common gynecologic malignancy nationally.¹ The mortality rate from endometrial cancer has increased over the last three decades. This increase in mortality rate likely is related to higher obesity rates, changes in reproductive trends, and lack of medical advances in this specific kind of cancer.^1,2 Additionally, significant racial disparities are seen, with Black women having worse survival outcomes in endometrial cancer regardless of histology or stage at diagnosis.^3,4

Abnormal uterine bleeding and postmenopausal bleeding are the most common presenting symptoms of endometrial cancer.⁵ In postmenopausal women, there is an algorithm for helping to determine who should undergo an endometrial biopsy to rule out endometrial cancer. Currently, transvaginal ultrasound is considered a first step in the evaluation of postmenopausal bleeding. If an endometrial thickness value is < 5 mm, no additional evaluation typically is required if the patient has not had repeated occurrences of bleeding, has a homogenous endometrium detected on imaging, and does not have endometrial fluid within the canal.

This was a retrospective diagnostic study analyzing data from the Guidelines for Transvaginal Ultrasound in Detection of Early Endometrial Cancer (GUIDE-EC) sample, which included data from 10 large academic health institutions between Jan. 1, 2014, and Dec. 30, 2020. The main objective of this study was to investigate the false-negative probability of transvaginal ultrasound endometrial thickness measurements to detect endometrial cancer in Black individuals. Inclusion criteria included Black patients who underwent transvaginal ultrasound within 24 months of having a hysterectomy. Patients were excluded if the pelvic ultrasound did not include information about the endometrium or if the endometrium could not be visualized on ultrasound. Demographic variables, clinical information, endometrial characterization from ultrasound, and whether individuals were diagnosed with endometrial cancer were collected from the database. For statistical analyses, chi-square tests and Fisher exact tests were used for categorical variables and two-tailed unpaired t-tests were used for continuous variables. Four endometrial thickness thresholds were used (< 3 mm, < 4 mm, < 5 mm, and > 5 mm). Sensitivity, specificity, and negative predictive value were calculated for each endometrial thickness threshold in detection of endometrial cancer. In addition, the false-negative probability, defined as 1-sensitivity, also was calculated for each endometrial thickness threshold.

Of the 3,455 cases reviewed from the GUIDE-EC sample, 1,494 individuals met inclusion criteria. A total of 210 (14%) individuals were diagnosed with endometrial cancer in the sample. The most common reasons for initial transvaginal ultrasound were fibroids, vaginal bleeding, and pelvic pain. In the < 3 mm threshold, eight cases of endometrial cancer likely would have been missed (representing a false-negative probability of 3.8%; 95% confidence interval [CI], 1.7% to 7.4%). With a < 4 mm threshold, 20 cases of endometrial cancer likely would have been missed (representing a false-negative probability of 9.5%; 95% CI, 5.9% to 14.3%). Increasing the endometrial thickness threshold to < 5 mm, 24 cases of endometrial cancer likely would have been missed (representing a false-negative probability of 11.4%; 95% CI, 7.5-16.5). Of note, when stratifying by age (those younger than 50 years and those older than 50 years), the false-negative probability was similar to that of the entire sample.

COMMENTARY

The American College of Obstetricians and Gynecologists (ACOG) currently recommends a transvaginal ultrasound as the initial step in evaluation of postmenopausal bleeding based on previous research suggesting that a homogenous, thin endometrial thickness of < 5 mm has a reported negative predictive value of more than 99%.⁶ This correlates with a < 1% chance of missing a malignancy if the endometrial thickness is < 5 mm. Interestingly, the authors reported that using this same threshold for ruling out endometrial cancer in a population of more than 1,400 Black individuals, 11.4% of individuals with endometrial cancer had an endometrial thickness < 5 mm, meaning the current strategy would have missed a cancer diagnosis for these individuals.

Although this study did include both premenopausal and postmenopausal women, when stratified by age, the false-negative probability did not change, demonstrating that the concern exists when only looking at the postmenopausal women in the sample as well. One important thing to note is that the studies used to help establish the < 5 mm cut-off for endometrial sampling in postmenopausal women all were completed outside of the United States: two in Nordic populations, one in an Italian population, and one in a Chinese population.^7-10 This ultimately may limit the generalizability of these findings to the United States populations and Black individuals.

Although reproducible findings are necessary prior to changing established guidelines, this study highlights the importance of having a lower threshold for endometrial sampling in Black individuals, especially given the disparities seen in mortality for Black women with endometrial cancer.

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