Postmenopausal Bleeding: Reliable Sign of Endometrial Cancer

Pam Harrison

August 08, 2018

Almost all women with endometrial cancer have a history of postmenopausal bleeding (PMB), although only a small minority of women with PMB will be diagnosed with endometrial cancer, a systematic review and meta-analysis has found.

"The projected rise in endometrial cancer incidence and mortality underscores the importance of strategies for early detection and prevention," write Megan Clarke, PhD, cancer prevention fellow, National Cancer Institute, Rockville, Maryland, and colleagues.

"This systematic review and meta-analysis…suggests that postmenopausal bleeding occurs in approximately 90% of women with endometrial cancer; however, only 9% of women with postmenopausal bleeding were diagnosed with endometrial cancer," investigators add.

"These findings provide a foundation for evaluating early detection strategies for endometrial cancer and can support risk-informed decision making in clinical management of postmenopausal bleeding," Clarke and colleagues suggest.

The study was published online August 6 in JAMA Internal Medicine.

The review and meta-analysis included 129 studies involving 40,790 patients. A total of  34,432 participants had a history of PMB while 6358 patients had been diagnosed with endometrial cancer.

Irrespective of tumor stage on diagnosis, "the pooled prevalence of PMB among women with endometrial cancer was 91%," the investigators report.

The pooled prevalence of PMB was even higher among women with stage I endometrial cancer, of whom 94% had a history of PMB.

However, this prevalence varied by geographic area and the use of hormone therapy. For example, among women with PMB,  the risk of being diagnosed with endometrial cancer was lowest in North American (5%) and Northern Europe (7%), whereas it was highest in Western Europe (13%).

The risk for endometrial cancer was also "notably lower" in studies in which women with PMB were taking hormone therapy.

This finding suggests that certain combinations of hormone therapy have a protective effect on the endometrium,  the study authors observe.

"Clinical practice guidelines currently recommend diagnostic workup of women presenting with PMB with transvaginal ultrasound, endometrial biopsy, and hysteroscopy with biopsy," Clarke told Medscape Medical News in an email.

"Our findings support these guidelines and provide reassurance that evaluating women with PMB will capture the majority of cancers at an early stage," she added.

Clarke also underscored that physicians should inform women that PMB can be a symptom of endometrial cancer and that they need to seek medical attention if they do experience this problem.

On the other hand, "clinicians also need to emphasize that PMB is associated with many benign conditions and that fewer than 1 in 10 women with PMB will be diagnosed with endometrial cancer," Clarke noted.

The authors also caution that the low positive predictive value of PMB as a diagnostic indicator of endometrial cancer in all women with PMB means there is a need for additional tests to improve the management of women with PMB and avoid unnecessary biopsies in women at low risk for the malignancy.

This point is taken up in the accompanying editorial, authored by Kristen Matteson, MD, MPH, Women and Infants Hospital, Providence, Rhode Island, and colleagues.

While the authors raise concerns about the positive predictive value of PMB as a marker of endometrial cancer, "rectal bleeding has a similar positive predictive value for colon cancer (8%) and palpable breast lumps have a similar positive predictive value for breast cancer (10%)," they point out.

Because further workup of both of these symptoms is routinely recommended, "evaluating 100 women with postmenopausal bleeding to diagnose 9 endometrial cancers does not seem excessive," they  suggest.

The editorialists also comment that  transvaginal ultrasonography of the endometrium is highly sensitive for detection of endometrial cancer and as such should be used as a first-line test to evaluate women with PMB.

"Many cancers are asymptomatic until advanced stages of disease when treatment has a minimal effect on survival," Matteson and colleagues observe.

"Endometrial cancer is quite different; 9 out of 10 women with early-stage disease present with symptoms of postmenopausal bleeding," they add.

Since not all women with PMB will have endometrial cancer, "risk needs to be appropriately communicated to patients," the editorialists continue.

"Overall, the results of this study will facilitate patient counseling," they conclude.

The study authors and the editorialists have disclosed no relevant financial relationships .

JAMA Intern Med. Published online August 6, 2018. Abstract, Editorial

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