Coexistence of Adenomyosis and Its Effect on Survival in Patients with Endometrial Cancer

and Aim: To investigate the impact of coexisting adenomyosis on clinicopathological char- acteristics and survival outcomes in patients who underwent surgery for endometrial cancer.

This retrospective, single-center cohort study included 124 patients who underwent surgi- cal treatment for endometrial cancer between January 2015 and May 2022. Patients were categorized according to the presence or absence of adenomyosis based on the final histopathological examination. Demographic characteristics, pathological findings, treatment modalities, recurrence, and survival out- comes were compared between the two groups.

Among the 124 patients, adenomyosis was identified in 31 (25.0%). Endometrioid carcinoma was the predominant histological subtype (91.3%). The coexistence of adenomyosis was significantly associated with the presence of leiomyoma (p=0.002), whereas no significant association was observed with tumor histology (p=0.766). The overall 3-year survival rate was 88.0%. The 3-year survival rates were 86.4% in patients with adenomyosis and 88.7% in those without adenomyosis, with no statisti- cally significant difference between the groups (p=0.427). Similarly, mortality rates did not differ signifi- cantly between the groups (22.6% vs. 18.3%, p=0.600).

Coexisting adenomyosis was detected in one-quarter of patients with endometrial cancer. Although adenomyosis was associated with concomitant leiomyoma, it was not associated with survival outcomes in patients with endometrial cancer.

Adenomyosis, endometrial cancer, hysterectomy, prognosis, survival

Endometrial cancer is the most common gynecological malignancy in developed countries and the second most common gynecological cancer in developing countries after cervical cancer. It is the fifth most frequently diagnosed cancer among women worldwide and remains an important cause of cancer-related morbidity and mortality.[1] The majority of patients present with abnormal uter- ine bleeding, leading to diagnosis at an early stage and consequently resulting in favorable survival outcomes. Endometrioid adenocarcinoma accounts for approximately 75–80% of all endometrial cancers, and surgical treatment remains the cornerstone of management.[1–4] Adenomyosis is a benign gynecological disorder characterized by the presence of endometrial glands and stroma within the myometrium, surrounded by hypertrophic and hyperplastic smooth muscle tissue.[4–8] It most commonly affects women between 40 and 50 years of age and is typical- Cite this article as: Polat OC, Hakverdi AU. Coexistence of Adenomyosis and Its Effect on Survival in Patients with Endometrial Cancer. Womens Health Multidisc Res 2026;2(2):32–37. Address for correspondence: Ozan Can Polat Department of Gynecology and Obstetrics, Buca Seyfi Demirsoy Training and Research Hospital, İzmir, Türkiye E-mail: [email protected] Submitted: 17.07.2026 Accepted: 05.08.2026 Online: 24.08.2026 Women’s Health and Multidisciplinary Research - Available online at www.whmresearch.com Copyright © Author(s) This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. Research Article

DOI: 10.14744/whmr.2026.05772 2026;2(2):32–37Womens Health Multidisc Res Polat and Hakverdi. Coexistence of Adenomyosis and its Effect 2026;2(2):32–37 33 Womens Health Multidisc Res ly associated with abnormal uterine bleeding, dysmenorrhea, and chronic pelvic pain. Histopathological examination remains the gold standard for diagnosis, and adenomyosis is reported in approximately 20–30% of hysterectomy specimens.[8,9] Several studies have demonstrated that adenomyosis fre- quently coexists with endometrial cancer, with reported prevalence rates ranging from 15% to 70%. [10] However, the clinical significance of this coexistence remains controversial. While some investigators have suggested that adenomyo- sis may contribute to myometrial invasion and influence tu- mor progression, others have reported that it may exert a protective effect by improving prognosis and survival. [11–14] Therefore, the prognostic value of coexisting adenomyosis in patients with endometrial cancer has not yet been clearly established. The present study aimed to evaluate the effect of coexisting adenomyosis on clinicopathological characteristics and survival outcomes in patients who underwent surgery for endometrial cancer.

This retrospective, single-center study included patients who underwent surgery for endometrial cancer at the Department of Obstetrics and Gynecology between January 1, 2015, and May 31, 2022. The study protocol was approved by Hatay Mustafa Kemal University Tayfur Ata Sökmen Hospital Non-in- terventional Clinical Research Ethics Committee (Approval Number: 11/2022, Date: 16.06.2022). Informed consent was obtained from all patients. This study was conducted in accor- dance with the principles of the Declaration of Helsinki. A total of 124 patients with histopathologically confirmed en- dometrial cancer who underwent at least total hysterectomy with bilateral salpingo-oophorectomy were included. Patients with incomplete medical records, those who continued fol- low-up at another institution, patients with metastatic tumors involving the endometrium, and those without reliable surviv- al data were excluded from the study. Medical records were reviewed retrospectively using the hospital information sys- tem, pathology reports, and the Turkish Ministry of Health Death Notification System. Patients were divided into two groups according to the pres- ence or absence of adenomyosis on final pathological exam- ination. The following variables were recorded: demographic characteristics (age, gravida, parity), accompanying systemic diseases, laboratory findings, preoperative imaging findings, endometrial biopsy results, histopathological characteristics, surgical procedures, adjuvant treatment, recurrence, mortal- ity, and survival outcomes. Histopathological evaluation of all surgical specimens was performed by experienced patholo- gists at our institution. The primary outcome of the study was to evaluate the effect of coexisting adenomyosis on survival in patients with endo- metrial cancer. Secondary outcomes included comparisons of clinicopathological characteristics, surgical findings, recur- rence, and mortality between patients with and without ade- nomyosis. Overall survival was defined as the interval from the date of primary surgery to death from any cause or the last confirmed follow-up. Patients who were alive at the end of follow-up were censored on the date they were last known to be alive. Vital status was determined using institutional medical records and the Turkish Ministry of Health Death Notification System. Overall survival was estimated using the Kaplan–Mei- er method, and survival curves were compared using the log- rank test. Three-year overall survival estimates are reported with 95% confidence intervals. The median follow-up duration was calculated using the reverse Kaplan–Meier method. A total of 124 patients with histopathologically confirmed pri- mary endometrial cancer were included in the final analysis. Of these, 31 had coexisting adenomyosis, whereas 93 had no adenomyosis on final histopathological examination. Adeno- myosis was diagnosed histopathologically by the presence of ectopic endometrial glands and stroma within the myometri- um, accompanied by surrounding smooth muscle hypertro- phy/hyperplasia. Cases in which apparent adenomyosis rep- resented only direct tumor extension into the myometrium were not classified as adenomyosis. Statistical Analysis The normality of continuous variables was assessed using the Kolmogorov–Smirnov test, Q–Q plots, and histograms. Contin- uous variables were expressed as the mean±standard deviation (SD) or median (minimum–maximum), as appropriate. Cate- gorical variables were presented as frequencies and percentag- es. Comparisons of categorical variables were performed using Pearson’s chi-square test or Fisher’s exact test. For compari- sons of continuous variables between two groups, the inde- pendent-samples t-test was used for normally distributed data, whereas the Mann–Whitney U test was used for non-normally distributed data. Univariate logistic regression analysis was per- formed to identify factors associated with adenomyosis. Agree- ment between Pipelle biopsy, dilatation and curettage (D&C), and the final surgical histopathological diagnosis was evaluated using Cohen’s kappa test. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic ac - curacy of Pipelle biopsy and D&C for detecting endometrioid carcinoma were calculated. Overall survival according to the presence of adenomyosis was analyzed using the Kaplan–Meier

and compared using the log-rank (Mantel–Cox) test. A two-sided p value of <0.05 was considered statistically sig- nificant. All statistical analyses were performed using IBM SPSS Statistics, version 22.0 (IBM Corp., Armonk, NY, USA). Polat and Hakverdi. Coexistence of Adenomyosis and its Effect 2026;2(2):32–37 34 Womens Health Multidisc Res

A total of 124 patients with histopathologically confirmed endometrial cancer were included in the study. Coexisting adenomyosis was identified in 31 patients (25.0%), whereas 93 patients (75.0%) had no evidence of adenomyosis on final histopathological examination. The mean age was comparable between patients with and without adenomyosis (59.0±10.1 vs. 60.3±10.2 years, p=0.545). Likewise, no significant differ- ences were observed between the two groups with regard to body mass index, gravida, parity, smoking status, diabetes mel- litus, hypertension, or menopausal status (p>0.05) (Table 1). Endometrioid carcinoma was the predominant histological subtype in both groups, accounting for 92.9% of patients with adenomyosis and 90.8% of those without adenomyosis. No significant difference was observed in the distribution of histological subtypes between the two groups (p=0.766). Similarly, tumor grade, tumor diameter, lymphovascular space invasion, depth of myometrial invasion, cervical stro- mal involvement, and adnexal involvement were compa- rable between patients with and without adenomyosis (all p>0.05). However, leiomyoma was significantly more fre- quent in patients with adenomyosis than in those without adenomyosis (45.2% vs. 17.2%, p=0.002). Overall, no sig- nificant association was found between adenomyosis and adverse histopathological prognostic factors in patients with endometrial cancer (Table 2). No significant differences were observed between patients with and without adenomyosis regarding the type of surgical procedure performed or the administration of radiotherapy or chemotherapy (p>0.05). During follow-up, recurrence was observed in 20 patients (16.1%). Recurrence rates were comparable between patients with and without adenomy - osis (19.4% vs. 15.1%, p=0.573). Similarly, no significant difference in overall mortality was observed between the two groups (22.6% vs. 18.3%, p=0.600). The mean over- all survival time was 44.0±26.4 months and did not differ significantly according to adenomyosis status (50.4±28.1 vs. 41.9±25.6 months, p=0.130) (Table 3). T able 1. Baseline demographic and clinical characteristics according to adenomyosis status Variables Adenomyosis (+) (n=31) Adenomyosis (−) (n=93) p n % n % Age (years), mean±SD 59.0±10.1 60.3±10.2 0.545 BMI (kg/m²), mean±SD 35.6±4.2 33.8±4.6 0.052 Gravida, median (min–max) 5 (0–9) 4 (0–12) 0.405 Parity, median (min–max) 4 (0–8) 4 (0–12) 0.530 Smoking 0.155 Yes 9 29.0 16 17.2 No 22 71.0 77 82.8 Diabetes mellitus 0.586 Yes 12 38.7 31 33.3 No 19 61.3 62 66.7 Hypertension 0.582 Yes 9 29.0 32 34.4 No 22 71.0 61 65.6 Cholecystectomy 1 3.2 13 14.0 0.186 Ileus surgery 1 3.2 1 1.1 0.439 Appendectomy 1 3.2 4 4.3 1.000 Menopausal status 0.799 Postmenopausal 24 77.4 74 79.6 Premenopausal 7 22.6 19 20.4 BMI: Body mass index, SD: standard deviation. T able 2. Histopathological characteristics according to adenomyosis status Variables Adenomyosis (+) (n=31) Adenomyosis (−) (n=93) p n % n % Final histopathology 0.766 Endometrioid carcinoma 26 92.9 79 90.8 Serous carcinoma 2 7.1 4 4.6 Clear cell carcinoma 0 0.0 3 3.4 Mucinous adenocarcinoma 0 0.0 1 1.1 Tumor grade 0.279 Grade 1 10 32.3 18 19.4 Grade 2 16 51.6 52 55.9 Grade 3 5 16.1 23 24.7 Tumor diameter (mm), median (min–max) 30.0 (2.0–67.5) 37.5 (2.0–180.0) 0.184 Lymphovascular space invasion 0.573 Present 4 12.9 16 17.2 Absent 27 87.1 77 82.8 Myometrial invasion, n (%) 1.000 <50% 21 67.7 63 67.7 ≥50% 10 32.3 30 32.3 Cervical stromal involvement 0.353 Present 2 6.5 14 15.1 Absent 29 93.5 79 84.9 Leiomyoma 0.002 Present 14 45.2 16 17.2 Absent 17 54.8 77 82.8 Polat and Hakverdi. Coexistence of Adenomyosis and its Effect 2026;2(2):32–37 35 Womens Health Multidisc Res

The present study investigated the association between coex- isting adenomyosis and clinicopathological characteristics, as well as survival outcomes, in patients with endometrial cancer. Adenomyosis was identified in 25% of the study population, a prevalence consistent with previous reports. Although leio- myoma was significantly more frequent in patients with ade- nomyosis, no significant associations were observed between adenomyosis and histological subtype, tumor grade, tumor di- ameter, myometrial invasion, lymphovascular space invasion, cervical stromal involvement, adnexal involvement, recur- rence, or overall survival. Furthermore, 3-year overall survival rates were comparable between patients with and without adenomyosis. These findings suggest that adenomyosis is not associated with more aggressive clinicopathological features or poorer oncological outcomes in endometrial cancer. The reported prevalence of adenomyosis in women with endometrial cancer ranges from approximately 15% to 70%. [10,11] This variability is likely related to differences in patient selection, pathological diagnostic criteria, and the extent of histopathological examination. Adenomyosis is defined by the presence of ectopic endometrial glands and stroma within the myometrium, surrounded by hypertrophic smooth muscle tis- sue.[8] Because its diagnosis relies on histopathological evalua- tion, variations in tissue sampling and pathological assessment may substantially influence the reported prevalence. In our study, adenomyosis was identified in 25% of hysterectomy specimens, supporting previous observations that adenomyo- sis frequently coexists with endometrial carcinoma. However, coexistence alone does not establish a causal relationship be- tween these two conditions. The prognostic significance of adenomyosis in endometrial can- cer remains controversial. Several studies have suggested that adenomyosis is associated with favorable pathological charac- teristics, including lower tumor grade, superficial myometrial invasion, earlier FIGO stage, and improved survival.[11–14] Pro- posed mechanisms include the hypertrophic myometrium sur- rounding adenomyotic foci acting as a mechanical barrier against tumor invasion, together with alterations in the local hormonal and inflammatory microenvironment. In contrast, other inves- tigators have found no association between adenomyosis and pathological prognostic factors or survival.[11] Our findings are consistent with these latter reports. We observed no significant differences between patients with and without adenomyosis regarding histological subtype, tumor grade, tumor diameter, myometrial invasion, lymphovascular space invasion, cervical stromal involvement, or adnexal involvement. The only signifi- cant pathological difference was the higher prevalence of leio- myoma in the adenomyosis group, a finding that is biologically plausible given the shared hormonal dependence and frequent coexistence of these two benign uterine disorders. The biological relationship between adenomyosis and endo- metrial cancer remains incompletely understood. Experimen- tal studies suggest that alterations in inflammatory mediators, extracellular matrix remodeling, angiogenesis, and steroid hormone signaling within adenomyotic tissue may influence tumor behavior.[8,12–14] These mechanisms have led to the hy - pothesis that adenomyosis may exert a protective effect by limiting local tumor spread or promoting earlier diagnosis through abnormal uterine bleeding. Nevertheless, the avail- able clinical evidence remains inconsistent, and our findings do not support a clinically meaningful protective or adverse effect of adenomyosis on tumor progression or prognosis. Similarly, adenomyosis was not associated with recurrence, mortality, mean overall survival, or 3-year overall survival in our cohort. Differences among published studies may reflect variations in sample size, patient characteristics, pathological evaluation, follow-up duration, surgical staging, and adjuvant treatment protocols. Consequently, the current evidence is T able 3. Treatment characteristics and oncological outcomes according to adenomyosis status Variables Adenomyosis (+) (n=31) Adenomyosis (−) (n=93) p n % n % Surgical procedure 0.279 TAH+BSO 2 6.5 10 10.8 TAH+BSO+PPLND 24 77.4 69 74.2 TAH+BSO+PPLND+ omentectomy 5 16.1 14 15.0 Radiotherapy 0.157 Received 17 54.8 64 68.8 Not received 14 45.2 29 31.2 Chemotherapy 0.799 Received 6 19.4 20 21.5 Not received 25 80.6 73 78.5 Recurrence 0.573 Present 6 19.4 14 15.1 Absent 25 80.6 79 84.9 Mortality 0.600 Alive 24 77.4 76 81.7 Dead 7 22.6 17 18.3 Overall survival (months), mean±SD 50.4±28.1 41.9±25.6 0.130 3-year overall survival (%) 86.4 88.7 0.427 BSO: Bilateral salpingo-oophorectomy, PPLND: Pelvic and para-aortic lymph node dissec- tion, SD: Standard deviation, TAH: Total abdominal hysterectomy. Polat and Hakverdi. Coexistence of Adenomyosis and its Effect 2026;2(2):32–37 36 Womens Health Multidisc Res insufficient to support adenomyosis as an independent prog- nostic marker in patients with endometrial cancer. The present study has several strengths. All patients were managed at a single tertiary referral center using relatively standardized surgical and postoperative treatment proto- cols, and all pathological specimens were evaluated within the same pathology department, thereby reducing interobserver variability. In addition, survival data were obtained from insti- tutional medical records and the national death notification system, minimizing incomplete follow-up. However, several

should be acknowledged. The retrospective design introduces the possibility of selection bias, the relatively small number of patients with adenomyosis may have limited sta- tistical power, and the single-center design may restrict the generalizability of our findings. Overall, our findings indicate that adenomyosis is a common histopathological finding in patients with endometrial cancer but is not associated with adverse clinicopathological char- acteristics or decreased survival. Although adenomyosis has been proposed as a potential prognostic factor, our results do not support its independent prognostic significance. Larger prospective multicenter studies with standardized pathologi- cal assessment are needed to further clarify the biological and clinical relationship between adenomyosis and endometrial cancer. The relatively small overall sample and, particularly, the limited number of patients with adenomyosis and death events reduced the statistical power of the survival analysis. The small number of outcome events precluded a reliable multivariable Cox proportional hazards analysis. Therefore, potential confounding by age, tumor stage, grade, histological subtype, treatment, and other prognostic factors could not be adequately controlled, and the absence of a statistically significant association should not be interpreted as evidence of prognostic equivalence.

Adenomyosis was identified in one-quarter of patients with endometrial cancer in the present study. Although leiomyoma was significantly more frequent among patients with adeno- myosis, no significant associations were observed between adenomyosis and unfavorable clinicopathological characteris- tics, including tumor grade, histological subtype, myometrial invasion, lymphovascular space invasion, cervical stromal in- volvement, recurrence, or survival outcomes. These findings suggest that adenomyosis is not an independent prognostic factor in patients with endometrial cancer. Nevertheless, giv- en the conflicting evidence in the current literature, larger pro- spective multicenter studies with standardized pathological evaluation are warranted to better clarify the biological and prognostic significance of adenomyosis in endometrial cancer. Ethics Committee Approval: The study was approved by the Hatay Mustafa Kemal University Tayfur Ata Sökmen Hospital Non-in- terventional Clinical Research Ethics Committee (Approval Number: 11/2022, Date: 16.06.2022). Informed Consent: Written informed consent was obtained from all the patients. Conflict of Interest: The authors have no conflicts of interest to de- clare. Funding: The authors declared that this study received no financial support. Use of AI for Writing Assistance: No use of AI-assisted technolo- gies was declared by the authors. Author Contributions: Concept – A.U.H.; Design – A.U.H; Super- vision – A.U.H; Resource – A.U.H; Materials – A.U.H; Data Collection and/or Processing – O.C.P .; Analysis and/or Interpretation – O.C.P .; Literature Review – A.U.H.; Writing – A.U.H.; Critical Review – A.U.H. Peer-review: Externally peer-reviewed.

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