Endometrial cancer is among the most common gynaecological malignancies worldwide. Among women with endometrial cancer, 90% initially report postmenopausal bleeding (PMB).1 2 3 4 5 Approximately 10% of postmenopausal women are estimated to experience PMB.1 Generally, there is no harmful underlying cause of PMB; however, women with recurrent PMB require medical assessment to distinguish between benign aetiology (eg, vaginal atrophy, uterine fibroids, and polyps) and endometrial cancer. Endometrial assessment is needed to exclude underlying malignancy.2 6 7 8 9 10

The endometrium can be examined non-invasively, using transvaginal sonography (TVS) to measure endometrial thickness (TVS-ET); alternatively, it can be examined invasively via blinded undirected endometrial sampling, saline infusion sonography, or diagnostic hysteroscopy.11 12 13 Although both TVS-ET and blinded endometrial sampling are recommended as first-line investigations,2 6 7 14 15 16 17 18 the gold standard approach for PMB investigation remains diagnostic hysteroscopy with visually guided endometrial sampling; this allows direct visualisation of the uterine cavity and histological investigation.19

Importantly, hysteroscopy is invasive and carries risks of complications such as infection, bleeding, uterine perforation, and visceral injury to the cervix or nearby organs (eg, bladder and bowel); it cannot be performed in women with cervical stenosis.20 Additionally, some women report that hysteroscopy is uncomfortable and painful within an out-patient or office setting; thus, hysteroscopy, cervical dilation, and uterine curettage have been performed under general anaesthesia in such cases. Although TVS-ET has become an established investigational tool, there remains a lack of consensus concerning the endometrial thickness (3, 4, or 5 mm) that constitutes ‘abnormal’. Our previous study of 4300 women with PMB demonstrated that 3% of women with PMB and endometrial thickness ≤3 mm had endometrial cancer.21

Patient preference regarding investigation approach is an important component of the decision care pathway. Individual women must balance the risks associated with an invasive procedure (eg, diagnostic hysteroscopy) with the risk of missing an endometrial cancer diagnosis if they select a non-invasive assessment (eg, TVS-ET). To our knowledge, the nature of this balance has not been assessed. The aim of the present study was to determine the extent to which women with PMB would accept the risk of missing endometrial cancer if they were to undergo TVS-ET as the first investigation of PMB.

This cross-sectional study was conducted in a tertiary centre in Hong Kong from June 2016 to June 2017. Women referred by either primary or secondary healthcare providers to the One-stop PMB Clinic for assessment and management were invited to participate in the study. Patient assessments included history taking, physical examination, pelvic ultrasound to measure endometrial thickness and screen for other pelvic pathologies, Pap smear (for women without recent Pap smear records), endometrial sampling with or without hysteroscopy. Women were excluded if they had <1 year of amenorrhea; had a prior TVS finding of endometrium thickness ≥5 mm; were aged ≥70 years; had dementia or mental retardation; and/or were unable to read or understand Chinese.

Prior to their clinic consultation, study participants completed a structured interview that was administered by an independent interviewer. Women were asked to first read an information leaflet regarding PMB, which described the risk of endometrial cancer, possible investigation options, and the risks associated with each option. The leaflet and interviewer explained that hysteroscopy and endometrial biopsy were expected to achieve a 100% detection rate, but these methods involved risks of pain, bleeding, infection, and uterine perforation related to uterine cavity exploration. The leaflet and interviewer also explained that TVS-ET did not require entry into uterine cavity but would potentially miss some cases of endometrial cancer. The leaflet and interviewer did not disclose the percentage of endometrial cancers that would fail to be detected by TVS-ET. After they had read the leaflet, women were asked to complete a study questionnaire regarding their sociodemographic characteristics and their personal and family histories of gynaecological cancer; they also completed the Chinese version of the 20-item State-Trait Anxiety Inventory to measure their trait and state anxiety levels. The women’s state and trait scores were categorised as above or below the scale midpoint. Women then underwent assessment of utilities regarding examination by either hysteroscopy or TVS-ET and the possibility of a missed cancer diagnosis, using the standard gamble technique.22

The standard gamble technique is the gold standard method used to determine utility towards a particular health state when a risk is involved. Individuals are asked to choose whether they prefer to have a certain guaranteed option or health state with a guaranteed outcome and no risk, or whether they would prefer an alternative option which entails some risk. The risks for the two health states are varied until the individual becomes indifferent to either option. At the point of indifference, the ‘utility’ for the health state under consideration is considered equal to ‘p’, while the utility of the alternative health state is considered equal to ‘1–p’.

Women were first asked to complete a standard gamble related to blindness, thereby ensuring that they understood the process. Subsequently, they were asked to complete a standard gamble to test their preferences towards the investigations of PMB. Each woman was asked to choose between the following tests: (1) TVS-ET, which is less invasive but involves some risk of missing endometrial cancer (probability of 1–p), or (2) an invasive test with hysteroscopy and endometrial biopsy, which detects 100% of all cancers but carries the risks described during the structured interview. To determine the level of acceptance of missing endometrial cancer during TVS-ET, the women were initially informed that the assumed detection rate of the TVS-ET was 75%; this detection rate was then increased in 5% intervals to 90%, then in 1% intervals to 98%, and finally in 0.1% intervals to 99.9%. We recorded the stated detection rate at which the woman was indifferent to either option. The missed endometrial cancer rate that women would accept to avoid an invasive procedure was defined as 1–detection rate.

Sociodemographic characteristics, past and current gynaecological history findings, and anxiety levels are presented as mean ± standard deviation or median and interquartile range; qualitative variables are presented as absolute frequency and percentage. The acceptable rate of endometrial cancer detection by TVS-ET alone, as an alternative to invasive hysteroscopy/biopsy, is presented as median and interquartile range. Differences in scores among sociodemographic groups were compared using the Mann-Whitney U test. SPSS software (Windows version 20; IBM Corp, Armonk [NY], United States) was used for all statistical analyses. A P value of <0.05 was considered statistically significant.

During the study period, 202 women agreed to participate in the study; 200 of these women completed the questionnaires and the standard gamble assessments. Table 1 summarises the sociodemographic, obstetric and gynaecological histories, and anxiety levels of these 200 women. Overall, 11 (5.5%) of the 200 women were subsequently diagnosed with cancer or an atypical endometrium: nine had endometrial cancer, one had cervical cancer, and one had atypical hyperplasia. Among 42 patients who underwent Pap smears in our clinic, smear results showed atypical glandular cells in two patients with endometrial cancer, while four patients with endometrial cancer had a shift in vaginal flora suggestive of bacterial vaginosis; the remaining smear results were normal.

The median endometrial cancer detection rate or utility that women would require for selection of TVS-ET to avoid invasive hysteroscopy examination was 95% (interquartile range=80%-99.9%). Overall, 77 (38.5%) women required TVS-ET to have a 99.9% detection rate for endometrial cancer. Thus, 38.5% of the women in our cohort would require TVS-ET to be comparable with diagnostic hysteroscopy before they would accept TVS-ET as the sole method for examination of the endometrium and uterine cavity.

Table 2 summarises the results of univariate analysis of the relationships between patient characteristics and the TVS-ET endometrial cancer detection rate. Women with previous hysteroscopy experience required the endometrial detection rate by TVS-ET to be significantly higher than did women without previous hysteroscopy experience (P=0.047). There were no significant differences in required endometrial cancer detection rates by TVS-ET among other sociodemographic characteristics, past and current obstetric and gynaecological histories, and state or trait anxiety (Table 2).

To our knowledge, this study is the first to utilise the standard gamble technique to evaluate patient preference with regard to approaches used for the investigation of PMB. Specifically, we assessed the extent to which women would prefer to avoid an invasive investigation (eg, hysteroscopy and biopsy) if a non-invasive alternative were available. Our findings suggested that TVS-ET would need to detect approximately 95% of endometrial cancers (or miss approximately 5% of endometrial cancers) for women to select TVS-ET with the intention of avoiding an invasive investigation. However, our analysis also suggested that nearly 40% of the participants required TVS-ET to detect nearly all endometrial cancers before they would select TVS-ET as the sole investigational approach.

There are sparse published data concerning patient preferences for the investigation of PMB. Our literature review revealed a single study by Timmermans et al.23 However, that study was limited to 39 participants and the results were obtained via telephone survey. In contrast to our protocol, Timmermans et al23 only assessed patient preferences after the women’s investigations had been completed; thus, their reported clinical experiences and preferences might have been biased. In the present study, we adopted the standard gambling approach which enabled a more quantitative analysis of patient willingness to select a different investigational approach. The standard gamble method is the gold standard approach for assessment of preferences in an uncertain situation24; it can be used to express the outcomes of different choices. It has been used previously to explore the acceptable risk of miscarriage after a high-risk Down syndrome screening test25 26 27 28; it has also been used to explore patient preferences concerning the risks of other medical treatments.

Currently, endometrial thickness cut-off values in endometrial pathology or cancer screening differ among hospitals.2 6 19 The most commonly used cut-off endometrial thickness value is 4 mm². Our study population of postmenopausal women accepted an endometrial cancer detection rate of 95% when using TVS-ET alone, with the intention of avoiding the more invasive procedure of hysteroscopy/endometrial biopsy. In our previous study, TVS-ET offered endometrial cancer detection rates of 97%, 94.1%, and 93.5% using 3 mm, 4 mm, and 5 mm as respective cut-off values.21 Thus, a TVS-ET cut-off of 3 mm would generally be consistent with the endometrial cancer detection accuracy that women in our study required for TVS-ET to be used as the sole investigational approach. In our study population, women with previous hysteroscopy experience required TVS-ET to have higher detection rates; hence, they preferred hysteroscopic assessment.

There were some limitations in our study. First, women aged ≥70 years were excluded because we presumed that they would have difficulty understanding the standard gamble technique and/or completing the study questionnaires without assistance. Second, although our sample size was sufficient to assess our primary goal, it was inadequate for subgroup analysis. Larger studies are needed to explore the relationships of specific patient characteristics with the acceptable rate of endometrial cancer detection by TVS-ET alone, particularly in relation to factors such as personal history of cancer or precancerous conditions. Finally, our findings concerning the acceptable rate of endometrial cancer detection by TVS-ET reflect the preferences of women who participated in our study; they may not be generalisable to populations with different sociodemographic characteristics or clinical management pathways.

Clinicians should incorporate patient preferences concerning the investigation of PMB to enable an informed choice about invasive testing to exclude endometrial cancer. Our study population accepted an endometrial cancer detection rate of 95% by TVS-ET alone; this rate could be used to guide the design of future PMB investigation strategies.

Concept or design: LWY Fung, ECW Cheung, ASW Wong, DS Sahota.
Acquisition of data: LWY Fung, ECW Cheung, ASW Wong, DS Sahota.
Analysis or interpretation of data: LWY Fung, DS Sahota.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: All authors.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

The authors acknowledge the clinical care provided by gynaecologists and nursing staff at the One-stop Postmenopausal Bleeding Clinic, Prince of Wales Hospital. We thank Miss Jennifer SF Tsang for her help with database management.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Ethics approval was obtained in August 2015 from The Joint Chinese University of Hong Kong–New Territories East Cluster Clinical Research Ethics Committee (CREC Ref 2015.437).

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