Postmenopausal bleeding: First steps in the workup
Is it endometrial cancer? When a postmenopausal woman presents with unexpected vaginal bleeding, this algorithm and review can help you answer that question without delay.
In a large cohort study (n=1535), EMB failed to provide an adequate tissue sample as much as 16% of the time.10 EMB’s sensitivity in detecting endometrial hyperplasia and cancer was 84%, the researchers reported, with a specificity of 99%; both the positive and negative predictive value were 94%. In a smaller study in which 97 women underwent TVUS and EMB was attempted, researchers reported that while no cases of endometrial cancer were missed when EMB sampling was successful, there was only a 27% probability of obtaining an adequate endometrial sample in women with an endometrial thickness (ET) <5 mm.11 EMB does a poorer job of detecting focal pathologies—with the potential to miss up to 18% of focal lesions, such as endometrial polyps, according to another study.12
Transvaginal ultrasound. TVUS is a safe, noninvasive, and cost-effective way to evaluate the endometrium, both to visualize focal lesions and assess ET. The technique, as defined by the SRU, involves scanning the uterus in a sagittal view and measuring the double-layer ET in the anteroposterior dimension from one basalis layer to the other.4
Reports of the sensitivity of TVUS in detecting endometrial cancer vary, depending on what cut point is used to rule it out. The SRU recommends an ET cutoff of ≤5 mm;4 ACOG recommends ≤4 mm.6 The consensus statements of both groups are based on a meta-analysis of 35 prospective studies that included data from nearly 6000 women with PMB. The sensitivity of TVUS in detecting endometrial cancer was 96%, whether the ≤4 or ≤5 mm cutoff was used, but specificity differed (53% for ≤4 mm vs 61% for ≤5 mm).13
In numerous studies with cut points of ≤4 or ≤5 mm, TVUS had a negative predictive value >99%.14-18 Because of this, ACOG states in an opinion issued in 2009 and reaffirmed in 2011, that TVUS is a “reasonable first approach.” The opinion further notes that in patients with an ET ≤4 mm, endometrial sampling is not required.6 In a meta-analysis of 3813 women, 3096 of whom were postmenopausal, researchers came to a different conclusion. An ET measurement on TVUS does not reduce the need for invasive diagnostic testing, the authors reported, because 4% of endometrial cancers would be missed even when a low threshold was used for reporting suspicious results.19
Type 2 endometrial cancer may be missed
A thin or indistinct endometrial lining on TVUS does not reliably exclude type 2 endometrial lesions20—which are not related to estrogen exposure or endometrial hyperplasia and typically present later in life, are diagnosed at a more advanced stage, and occur less frequently than type 1 endometrial cancer. A retrospective review of 52 patients with type 2 endometrial cancer found that 17% had an ET <4 mm, and another 17% had an indistinct endometrium.20
Factor risk level into decision-making
Researchers who conducted a decision analysis found that EMB is a more cost-effective initial diagnostic test for populations with a prevalence of endometrial cancer ≥15%.21 Overall, the prevalence among postmenopausal women in the United States is roughly 0.7%,22 but it is considerably higher among women with polycystic ovarian syndrome, obesity, diabetes, early menarche, late menopause, nulliparity, a history of tamoxifen use, or hereditary nonpolyposis colorectal cancer.5 For women with PMB and any of these risk factors, physicians should consider EMB as the first diagnostic test.
Because EMB is a substandard test for diagnosing benign endometrial abnormalities, such as polyps and submucosa leiomyomas, TVUS may be a better starting point for women at lower risk for endometrial cancer. In any case, an ET >4 mm requires further investigation using EMB, saline infusion sonography (SIS), or hysteroscopy with biopsy.9 Patients with uterine pathology noted with TVUS should be referred for treatment.
Next step? Consider saline infusion sonography
SIS is a procedure in which sterile saline is infused into the endometrial cavity, then TVUS is performed. The saline solution distends the uterus, promoting visualization and thus providing more detail than a conventional ultrasound.
Because SIS is expensive and uncomfortable, it is used mainly as a second step in the evaluation of PMB. It is useful when:
