Clinical characteristics for unexpected endometrial cancer following hysterectomy for pelvic organ prolapse repair

Introduction

Pelvic organ prolapse (POP) is a common problem with a prevalence rate of over 50% in women over 50 years old.1 2 The factors that lead to POP vary from patient to patient, including genetic factors, pregnancy and birth injuries, ageing, menopause, lifestyle and comorbidities.3 4 The main treatment for patients with moderate to severe prolapse is surgical treatment, which includes many variations, including hysterectomy, sacral vaginal fixation, sacral spinous ligament fixation, vaginal suturing, perineal suturing, colpocleisis and so on, depending on the location of pelvic floor defects.5

Although hysterectomy has traditionally been incorporated into most surgical procedures for POP repair, particularly for middle compartment defects, a Cochrane systematic review concluded that there were no significant differences in primary outcomes between vaginal hysteropexy and vaginal hysterectomy for uterine prolapse, nor between vaginal hysteropexy and abdominal hysteropexy/cervicopexy.6 The uterine sparing procedure was emerging and prevailing. There was an inconsistency on whether the uterus should be removed during the pelvic floor repair surgery or not. The existing literature has reported that the incidence of occult endometrial cancer diagnosed after pelvic floor repair surgery ranged from 0.3% to 1.1% in the UK and the USA7–10, even when the woman had routine preoperative ultrasonography and related examinations. However, there were a few reports from China and other Asian countries that were entering the advanced-ageing society. Thus, the consideration of the risk factors of anticipated malignancy specifically one of the most prevalent gynaecological malignancies, the endometrial cancer, should be additionally taken into account to determine whether to remove the uterus or not during the surgical planning.

To address this knowledge gap, we analysed clinical characteristics in our patient population to identify potential high-risk factors. These findings provide preliminary descriptive data on the clinical features of occult endometrial malignancy in POP patients, which may inform the design of future prospective studies aimed at defining high-risk criteria and guiding preoperative endometrial evaluation strategies.

Materials and methods

From July 2008 to January 2024, the cases of endometrial cancer detected after operation of vaginal hysterectomy for the treatment of POP were recruited. The medical records of women undergoing surgery at Peking University People’s Hospital for the treatment with vaginal hysterectomy were reviewed and analysed.

This study has been reviewed and approved by the institutional IRB committee at Peking University People’s Hospital (2024PHB539-001). This retrospective study searched for diagnoses of ‘prolapse’ and ‘endometrial cancer’ with the procedure ‘hysterectomy’ at Peking University People’s Hospital from July 2008 to January 2024. Screening first identified all patients who underwent hysterectomy for prolapse. It then selected those with a postoperative pathological diagnosis of endometrial cancer who had no relevant preoperative clinical manifestations, no suggestive findings on auxiliary examinations, and no standard indications for preoperative endometrial biopsy at the time of their prolapse surgery assessment.

Data were standardised, thoroughly collected, and reviewed through the electronic medical records system. Analyses included (1): demographics (age, body mass index (BMI), pregnancy, menstrual status, etc); (2) main diagnosis; (3) main symptoms and medical history; (4) physical and laboratory examinations; (5) pathological reports and outcomes.

Inclusion criteria for study subjects were (1) patients who underwent vaginal hysterectomy for POP at Peking University People’s Hospital between January 2008 and February 2024; (2) patients with unexpected postoperative pathological diagnosis of malignant endometrial lesions; (3) patients who were asymptomatic preoperatively and whose preoperative auxiliary examinations (eg, ultrasound, tumour markers) were negative or non-suspicious for malignancy.

Exclusion criteria were (1) patients presenting symptoms suggestive of endometrial malignancy (eg, abnormal vaginal bleeding) or abnormal auxiliary examination results preoperatively; (2) patients with a confirmed preoperative biopsy diagnosis of endometrial pathology; (3) POP patients whose postoperative pathological examination revealed no malignant lesions. SPSS V.27.0 was used for data analysis. Measurement data that conform to a normal distribution are represented by mean±SD (χ±s), and intergroup comparisons are conducted using t-test or one-way analysis of variance. The data that do not conform to the normal distribution are represented by the median (25th percentile, 75th percentile) (M (P25, P75)) and the Mann-Whitney U test is used for inter-group comparison. Count data are expressed as percentages (%), and between group comparisons are performed using χ² test or Fisher’s exact test. p<0.05 indicates a statistically significant difference.

Results

Through the electronic medical record searching, there were a total of 3588 women in 7472 prolapse surgical cases who had concurrent hysterectomy during pelvic floor repair between July 2008 and January 2024. Before hospitalisation, all patients had a routine Pap smear or cervical cytology test (ThinPrep cytologic test) and high-risk HPV testing (Hybrid Capture 2 High-Risk HPV DNA Test, or Aptima HPV Assay) within 1 year or performed in the outpatient setting as well as a transvaginal ultrasound with colour Doppler flow imaging. Forty-three women who asked for surgical treatment for prolapse and had a pathological diagnosis of endometrial malignancy were retrieved, among which 11 women were unexpectedly diagnosed with endometrial cancer without obviously preoperative malignant evidence after the hysterectomy with pelvic floor repair surgery, the other 32 got the malignant pathological results through the prior hysteroscopy and/or dilation and curettage and transferred to the gynaecologic oncologist for the standardised treatment first. These diagnoses and treatment processes are strictly in accordance with the endometrial screening guidelines of The American College of Obstetricians and Gynecologists (ACOG), the National Comprehensive Cancer Network (NCCN), and the Chinese expert consensus.11–13 Our study cohort included 32 cases that underwent preoperative endometrial biopsy, all of which yielded definitive pathological diagnoses. However, our analysis specifically focused on the remaining 11 patients who did not meet indications for preoperative biopsy, in whom endometrial carcinoma was unexpectedly identified following pelvic floor reconstructive surgery. These cases underwent comprehensive clinical characterisation using all available perioperative data. These patients’ details are shown in table 1.

Discussion

This study aimed to delineate the clinical features of unanticipated endometrial cancer cases undetected by standard screening protocols following pelvic floor surgery and to conduct exploratory analyses to inform future cohort studies on high-risk factors in this patient population. The study conducted a large-scale, single-centre, retrospective review of 7472 surgical repair cases from July 2008 to January 2024. The incidence of unexpected endometrial malignancy in our cohort was 0.31% (11/3588), which is at the lower end of the 0.3%~1.1% range reported in the literature.7–10 There was an inconsistency on whether the uterus should be removed during the pelvic floor repair surgery or not in both specialists’ opinions and clinical studies. The fact that traditionally, hysterectomy, specifically vaginal hysterectomy, had been a basic procedure that almost all prolapse patients underwent in the surgical pelvic floor repair, while with the improvement of the surgical approaches for applying synthetic materials and optimised native tissue repair, there was an emerging tendency towards uterine sparing techniques, specifically for shortening the operation time and decreasing the surgery morbidity in the elderly cohort. However, there are potential disadvantages to preserving the uterus, most notably the risk of occult malignancy. Multiple studies, including a systematic review and meta-analysis, have confirmed that unexpected uterine malignancy can be identified even after comprehensive preoperative evaluation at tertiary referral centres, underscoring that negative workup does not fully exclude malignant pathology in this population.22–24

The characteristics of the identified eleven patients were systematically analysed. The occult cases were usually endometrioid carcinoma with low histological grade and early pathological stage; 7 of 11 cases demonstrated superficial myometrial invasion (<1/2 myometrial thickness), and the remaining 4 had lesions confined to the endometrium. Endometrial cancer in patients with POP often presents with atypical manifestations. Even when patients possess typical high-risk factors, such as metabolic syndrome (particularly overweight and obesity), hypertension, diabetes and cardiovascular diseases, the diagnosis remains challenging. Clinically, advanced anterior and middle compartment prolapse represents the most common indication for surgical intervention; however,friction-induced bleeding and ulcerative discharge resulting from vaginal wall abrasion are frequently misattributed to mechanical irritation, thereby masking underlying malignant lesions. Decubitus ulcers secondary to prolapse are well documented, with a prevalence of approximately 35% in advanced POP.25 Moreover, recent case series have highlighted that POP-related symptoms may confound the clinical presentation and delay the diagnosis of concomitant gynecologic malignancies26 .This diagnostic ambiguity often renders it difficult for urogynecologists to decide whether to perform diagnostic curettage or hysteroscopy in asymptomatic patients with negative ultrasound findings. Furthermore, even when tumour marker screening is incidentally conducted during outpatient visits or routine physical examinations, negative results may provide false reassurance and inadvertently delay the indication for endometrial biopsy.

This study summarised the clinical features of occult endometrial malignancy specifically in women suffering POP. The presenting ACOG, NCCN and Chinese expert consensus guidelines all shared the basic strategy that, for asymptomatic low-risk and ultrasound-negative postmenopausal women, endometrial biopsy and/or hysteroscopy were not routinely recommended.11–13We summarised the brief clinical characteristics of 11 cases of occult endometrial cancer in table 1, additional detailed information has been provided in online supplemental table 1, when there was only a weight issue, up to 60% individuals can be detected, when there were overweight with one metabolic syndrome complication, up to 10 out of 11 cases can be detected, while there were overweight with two or more metabolic syndromes, up to 100% of occult endometrial cancer patients can be detected.These cumulative detection patterns define a clinically meaningful high-risk profile: asymptomatic postmenopausal women with overweight or obesity (BMI ≥24 kg/m2 by Chinese criteria) combined with two or more metabolic syndrome components including hypertension, diabetes, hyperlipidaemia, cardiovascular disease, or fatty liver disease represent the subgroup in whom preoperative endometrial evaluation appears most warranted. All 11 cases of occult endometrial malignancy in our cohort fell within this profile, suggesting it as a practical screening criterion for urogynecological practice, pending validation in larger prospective studies. The complete clinical information for all 11 patients has been compiled in online supplemental table 2, we recommend that for the prolapse women with prolapse who are seeking uterus-preserving pelvic reconstruction, if the patient has weight-related concerns with more than one metabolic syndrome factor (online supplemental table 1), additional endometrial biopsy or hysteroscopy might be required preoperatively, for further evaluation to rule out malignancy.

The strength of this study lies in its status as alarge-scale, long-term retrospective cohort analysis of occult endometrial cancer characteristics in POP patients’ postreconstruction, conducted at a national tertiary referral centre with standardised diagnostic protocols and incorporating comprehensive demographic, medical history and clinical examination data from surgically managed cases. Current guidelines do not recommend routine endometrial biopsy for asymptomatic, examination-negative postmenopausal women. However, this recommendation was developed in the context of general gynaecological care, not specifically for women planning uterine-preserving pelvic floor reconstruction. In the latter scenario, the uterus is retained and no histological specimen is obtained; occult malignancy therefore goes undetected. For women in this setting who carry the high-risk profile described above, targeted preoperative endometrial biopsy or hysteroscopy represents a reasonable and clinically justified additional evaluation step, distinct from routine population-level screening. Accordingly, uterine-sparing surgical planning should be approached with caution in this subgroup, and the decision to preserve the uterus should incorporate a careful assessment of endometrial malignancy risk. The limitation is that this is a single-centre, retrospective study with a small sample size, and some medical records are incomplete due to the long time span. In the future, it is necessary to increase the sample size and conduct multicentre cohort studies to collect sufficient data for further statistical analysis.

Conclusion

Unexpected endometrial malignancy during pelvic organ prolapse (POP) repair is rare (0.31%) but occurs despite normal preoperative ultrasound and tumour markers, predominantly in overweight/obese women with metabolic syndrome. Consequently, targeted preoperative endometrial evaluation should be considered for asymptomatic women with this high-risk profile, particularly those planning uterine-preserving surgery. Further prospective studies are required to validate these risk-stratification criteria.