postmenopausal bleeding and endometrial cancer

A systematic review and meta-analysis found that postmenopausal bleeding preceded the vast majority of diagnoses of endometrial cancer, though only a small minority of women with postmenopausal bleeding in fact had cancer (see postmenopausal bleeding review jamaintmed2018 in dropbox, or doi:10.1001/jamainternmed.2018.2820 ).

Details:

--21 studies were found between 1977-2017 that included the analysis of the prevalence of postmenopausal bleeding (PMB) in women with endometrial cancer: 3792 cases of cancer, 3257 of whom had PMB

--92 studies were found to assess the risk of endometrial cancer in women with PMB: 31,220 women with PMB, 2611 of whom had cancer

Results:

--Prevalence of PMB in women with endometrial cancer

    --overall prevalence of PMB was 90%

    --similar % if limit study outliers, ie no difference in outcome if less variance between studies

    --by tumor stage:

        --in the 5 studies with stage I tumors (with 95% 5-yr survival): 94% had PMB

        --in those with stages II to IV tumors: 84% had PMB (this was not significantly different by stage)

            --Stage IV cancer has 5-year survival from 16-45%

    --by geographic region: no difference if from North America (94%) to Western Asia (90%) to Eastern Asia (95%)

    --earlier studies had slightly higher rate of PMB (decreased to 86% in studies from 2010-17)

--Risk of endometrial cancer in women with PMB

    --overall, 9% of those with PMB had endometrial cancer, with moderate variability between the studies

        --in studies that excluded hormone therapy (HT), 12% had cancer, vs 7% in those that included HT

    --by geographic region: lowest in North America (5%), and Northern Europe (7%) and highest in Western Europe (13%)

        --excluding women with HT, still with regional differences

    --in the 10 studies including women with PMB and minimum endometrial thickness of 4-5mm, pooled risk of endometrial cancer was 19%

    --in 7 studies in women with PMB and polyps, pooled risk was 3%

Commentary:

--endometrial cancer is most common gynecologic cancer (5% of cancer cases and >2% of deaths due to cancer in women worldwide) and is one of the cancers which has been increasing over time. It is more common in industrialized countries, may be related to known risk factors of: obesity, early menarche, late menopause, nulliparity, and postmenopausal estrogen use

--the issue of use of hormone therapy is a tad unclear in the above study, since just giving estrogen promotes the endometrial cancer, but the combo with progestins actually decreases the cancer risk. This study was unable to differentiate these differences in HT approaches

--one difference in the US vs European approaches to PMB is that in many European countries, transvaginal ultrasound (TVUS) is the first-line evaluation, with biopsy if the endometrial thickness is >3-5mm.  The US guidelines recommend either TVUS or endometrial biopsy.

--the sensitivity of endometrial biopsy for cancer is 99.6% and the specificity is 98-100%

--TVUS is not quite that impressive: using a cutpoint of 4mm thickness the sensitivity is 95%; using a 5mm thickness, it decreased to 90%. Some studies suggest using a cutpoint of 3mm to exclude endometrial cancer (eg, see Timmermans A. Obstet Gynecol. 2010; 116(1): 160.)

So, a useful study in that it highlights the high sensitivity of postmenopausal bleeding for endometrial cancer detection as well as the high pickup rate in those with stage I and largely curable cancer.  Given the really high sensitivity/specificity of endometrial sampling and the low risks associated with this office procedure, it may make sense that this be the preferred test. Especially since there are cancers with the 4-5mm endometrial thickness on TVUS, and lowering the limit to 3mm will significantly increase the false positivity rate and mostly just delay the diagnosis (sort of like just doing fine-needle biopsies of thyroid nodules instead of the intermediary step of ultrasound)

geoff

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