Long-term Risk of Endometrial Cancer Following Postmenopausal Bleeding and Reassuring Endometrial Biopsy

ABSTRACT
Women with postmenopausal bleeding who present with an endometrial thickness 4 mm or less are at a very low risk of endometrial cancer, and therefore refraining from endometrial sampling in these women is considered justified. If the endometrial thickness is more than 4 mm, endometrial sampling is indicated to exclude endometrial cancer. Although women with a histological finding of endometrial hyperplasia without atypia have a slightly increased risk of developing endometrial cancer, this finding is generally regarded as a reassuring histology without the need for further follow-up. A recently published prospective cohort study reported that in 84 (29.8%) of 356 women presenting with postmenopausal bleeding and endometrial thickness of more than 4 mm, outpatient endometrial sampling failed because the amount of tissue was insufficient for a reliable histopathologic diagnosis. When endometrial sampling fails, there is currently no consensus on what to do. No long-term follow-up studies have reported the incidence of endometrial cancer after failure of endometrial sampling. The aim of this long-term cohort follow-up study was to investigate the relative risk of developing endometrial cancer after initial workup for postmenopausal bleeding shows reassuring histology or insufficient endometrial sampling. The authors hypothesized that women with postmenopausal bleeding and failure of endometrial sampling have an increased risk of endometrial (pre)malignancies. Participants were women with postmenopausal bleeding presenting at 3 hospitals in the Netherlands between January 2009 and April 2011. Long-term follow-up data were collected from the patient charts of the 3 participating hospitals and from PALGA, the Dutch Pathology Registry. Standardized incidence ratios were calculated to estimate the risk of endometrial cancer, relative to the general population. A total of 668 women presented with postmenopausal bleeding; of these, 568 were available for follow-up. Median follow-up time was 47 months (range, 7–63 months). Women with postmenopausal bleeding, endometrial thickness of more than 4 mm, and hyperplasia without atypia on biopsy at the first presentation had a 17 times increased risk of developing endometrial cancer during the first 4 years of follow-up compared with the age-specific population; the standardized incidence ratio was 17.15, with a 95% confidence interval of 1.96 to 61.93. All women who developed endometrial cancer after initial reassuring histology presented with recurrent postmenopausal bleeding. During follow-up, no endometrial cancer was diagnosed in women with endometrial thickness of more than 4 mm and no or insufficient histology at initial presentation. Despite an initial reassuring histological finding of endometrial hyperplasia without atypia, women with postmenopausal bleeding and endometrial thickness of more than 4 mm had a significantly increased risk of endometrial cancer during 4 years of follow-up compared with the age-specific population. Further studies are needed to determine whether additional diagnostics or a more stringent follow-up regimen would be cost-effective.