{"paper_id":"c4a7d26e-9977-4842-8086-b3037a1edce5","body_text":"Endometrial cancer (EC), a malignancy of the uterine endometrium, is increasing in prevalence and is projected to become the leading gynecologic cancer globally [ 1 ]. EC is the sixth most common cancer globally and is a significant contributor to morbidity and mortality [ 2 ]. In 2023, EC was the most common gynecologic cancer in the United States, with over 66,000 new cases and 13,000 deaths expected [ 3 ]. Both the incidence and annual death toll of EC have risen in recent years [ 4 ]. The rise in EC incidence is attributed to risk factors like early menarche, late menopause, obesity, diabetes, nulliparity, advanced age (≥55 years), and tamoxifen use. Increased mortality is linked to inconsistent pathological risk stratification. Most cases are uterine-confined at diagnosis, with favorable survival outcomes [ 5 ]. Key predictors of cancer outcomes are histological type, tumor grade, tumor size, degree of myometrial invasion, lymph node involvement, and disease stage [ 6 ]. Endometrial hyperplasia, characterized by abnormal endometrial thickening due to estrogen-progesterone imbalance, is a precursor to endometrial cancer, particularly in cases with atypia. While <5% of non-atypical hyperplasia progresses to malignancy, approximately 28% of atypical hyperplasia cases develop into endometrial cancer within 20 years, underscoring the need for vigilant clinical management [ 7 ].\nAdenomyosis is characterized by the infiltration of endometrial glands and stromal tissue into the myometrium, typically occurring in women aged 40–50 years [ 8 ]. Its exact etiology is unclear, but potential factors include hormonal imbalances, inflammation, and genetic predisposition. Estrogen plays a significant role in its development, as adenomyosis tends to regress after menopause when estrogen levels decline [ 9 ]. It is a common histopathological finding in surgical specimens from patients with gynecological conditions.\nRecent research suggests that adenomyosis may be a precursor to EC [ 10 ]. When the uterus is removed during surgery and sent to pathology for examination, adenomyosis, alongside cancer, is among the most frequently diagnosed histopathological findings by pathologists [ 2 ]. Adenomyosis and EC share common risk factors and biological mechanisms, such as increased estrogen, genetic mutations, and inflammation, which promote abnormal tissue growth and cancer development [ 11 ].\nStudies present conflicting views on the coexistence of adenomyosis and EC. Some link it to improved prognosis [ 12 ,  13 ], while others report no prognostic impact [ 2 ,  5 ,  14 ] or an association with aggressive features like deep myometrial invasion and LVSI [ 15 ]. This discrepancy raises critical questions about the nature of adenomyosis in the context of EC: Is it a biological contributor, a precursor, or merely an incidental finding? Although adenomyosis and EC are frequently co-diagnosed in hysterectomy specimens, the prognostic implications of adenomyosis in EC remain uncertain. Current literature is limited by inconsistent methodologies, small sample sizes, and contradictory findings. These limitations hinder a comprehensive understanding of whether adenomyosis independently influences tumor behavior and patient outcomes or simply coexists without significant biological impact.\nThis study addresses this gap by systematically evaluating the role of adenomyosis in EC. We aim to determine whether adenomyosis serves as a biological contributor to tumor progression or is an incidental finding without prognostic significance.\n\nThis retrospective cohort study was conducted at the First Affiliated Hospital of Zhengzhou University from 1 st  January 2019 to 31 st  December 2024 which included 388 patients with endometrial cancer (EC) who underwent hysterectomy with bilateral salpingo-oophorectomy and pelvic/para-aortic lymphadenectomy. Ethical approval was obtained (No. 2024-KY-0671-001), and informed consent was waived due to the study’s retrospective nature. All surgeries were performed using minimally invasive techniques (MIS). Uteri ≤12 weeks in size were typically removed vaginally [ 16 ], For larger uteri (>12 weeks), techniques such as transvaginal bivalving, morcellation, or myomectomy were employed to reduce uterine size for easier removal [ 17 ]. Bivalving splits the cervix and lower uterus, facilitating extraction, while coring involves a circumferential incision at the internal cervical os to remove myometrial sections [ 17 ]. Both techniques soften and mobilize the uterine body, enhancing accessibility [ 18 ]. To prevent pelvic cavity contamination, uterine fragments were contained in specimen retrieval bag during removal, ensuring complete and secure extraction.\nHistological sections were re-examined independently by two pathologists blinded to the original results. Adenomyosis was diagnosed by identifying endometrial glands and stroma embedded in the myometrium, at least 2.5 mm from the endometrial-myometrial junction. The uterus, including the cervix and lower uterine segment, was divided into six regions to assess tumor invasion and adenomyosis involvement. Depth of invasion was classified as superficial (< 50% myometrial thickness) or deep (≥ 50%), and tumor proximity to adenomyosis was noted as direct contact or separated by normal myometrium. Adenomyosis morphology, including cystic degeneration and fibrosis, and tumor interactions were analyzed. Immunohistochemistry assessed epithelial-mesenchymal transition (E-cadherin, N-cadherin) and angiogenesis (CD34, VEGF). All cases were re-evaluated to ensure consistent and thorough assessment.\nThe primary objective was to assess the coexistence of adenomyosis and EC, while the secondary objective evaluated its impact on tumor progression. Collected data included patient demographics (age, parity, BMI, menarche/menopause age, comorbidities, family history), preoperative findings (CA125, imaging, TCGA subtypes: POLEmut, MMR-d, NSMP, p53abn), histopathological characteristics (histologic subtype, grade, depth of invasion, LVSI, LNM, hyperplasia), tumor markers (p53, p16, ER, PR), and FIGO staging (2009 and updated 2023). Postoperative complications (DVT, pulmonary inflammation, anemia, urinary infections) and adjuvant treatments (radiation, chemotherapy, hormonal therapy) were documented. Follow-up involved clinical exams, imaging (ultrasound, MRI, CT), tumor markers, and biopsies through telephone, outpatient, or hospitalization records. Survival analysis was performed using the Kaplan–Meier method and log-rank test. Disease-free survival (DFS) was defined as the time from surgery to the first recurrence of disease or the last follow-up without recurrence. Kaplan–Meier survival analysis was used to estimate DFS, and differences between groups were evaluated using the log-rank test. Due to the limited number of recurrence events, multivariate Cox regression analysis was not feasible. DFS outcomes are presented as supplementary material.\nDescriptive and comparative statistical analyses were performed to evaluate the data. For continuous variables, medians and inter quartile ranges (IQR) were calculated, while frequencies and percentages were used for categorical variables. The Mann–Whitney U test (represented by W) was applied to compare continuous variables between the groups, and the chi-square test (χ2) was used to compare categorical variables. No correction for multiple comparisons was applied due to the exploratory nature of the study.  P -values were calculated to assess the statistical significance of differences, with a threshold of  P  < 0.05 considered statistically significant. The analyses were conducted using SPSS software (Statistical Package for the Social Sciences) 26.0.\n\nIn our study, total 388 patients were included, in which 73 patients 18.8% had both endometrial cancer and adenomyosis. The assessment of demographic data and surgical procedures and outcomes are done in Table  1 .\n Table 1 Baseline characteristics demographic and surgical variable Characteristics Adenomyosis ( n  = 73) No adenomyosis ( n  = 315) Test statistic (W/χ2) P - value Age 52.0(48.0, 56.0) 55.0(50.0, 59.0) W = 13,683 0.011 Menarche 13.0(13.0, 15.0) 14.0(13.0, 15.0) W = 9820 0.060 Parity 2.0(1.3, 2.0) 2.0(2.0, 2.0) W = 11,426 0.926 BMI 25.3(24.1, 28.8) 24.6(23.4, 27.0) W = 12,554 0.221 Hypertension χ2 = 0.068 0.793  Yes 23(31.5) 95(30.2)  No 50(68.5) 220(69.8) Diabetes χ2 = 0.922 0.337  Yes 10(13.7) 61(19.4)  No 63(86.3) 254(80.6) Menopause χ2 = 3.89 0.049  Yes 46(63.0) 237(75.2)  No 27(37.0) 78(24.8) Surgical method χ2 = 3.306 0.069  RALH 21(28.8) 58(18.4)  LH 52(71.2) 257(81.6) Adjuvant therapy χ2 = 5.890 0.015  Yes 16(21.9) 119(37.8)  No 57(78.1) 196(62.2) Postop complications χ2 = 0.211 0.646  Yes 24(32.9) 120(38.1)  Mild anemia 13(17.8) 25(7.9) Lungs inflammation 7(9.6) 45(14.3) Urinary tract infection 1(1.4) 10(3.2) Deep venous thrombosis 3(4.1) 40(12.7) No 49(67.1) 195(61.9) Treatment outcome Recurrence 1.0  Yes 0 2(0.6)  No 73(100%) 313(99.4) Value are given as number (range or %) unless otherwise noted. Mann–Whitney U test (represented by W), chi-square test (χ2) BMI  Body mass index,  RALH  Robotic assisted laparoscopic hysterectomy,  LH  Laparoscopic hysterectomy\nBaseline characteristics demographic and surgical variable\nValue are given as number (range or %) unless otherwise noted. Mann–Whitney U test (represented by W), chi-square test (χ2)\nBMI  Body mass index,  RALH  Robotic assisted laparoscopic hysterectomy,  LH  Laparoscopic hysterectomy\nA comparative analysis revealed no statistically significant differences between the adenomyosis and non-adenomyosis groups regarding age at menarche ( P  = 0.060), parity ( P  = 0.926), BMI ( P  = 0.221), or comorbidities such as hypertension ( P  = 0.933) and diabetes mellitus ( P  = 0.316). Surgical approach also showed no significant variation ( P  = 0.069). However, patients with adenomyosis were diagnosed at a younger median age ( P  = 0.011) and exhibited a lower prevalence of menopause (63.0% vs. 75.2%,  P  = 0.049). The adenomyosis group required adjuvant therapy significantly less often (21.9% vs. 37.8%;  P  = 0.015). No recurrences were observed in the adenomyosis cohort, whereas two recurrences occurred in the non-adenomyosis group at 38.7 and 40.2 months postoperatively (log-rank test,  P  = 0.66). Due to the limited number of recurrence events, DFS analysis could not be adjusted for potential confounders, and results should be interpreted cautiously (Figure_S1).\nPostoperative complications were observed in 32.9% of patients in the adenomyosis group and 38.1% of patients in the non-adenomyosis group, with no statistically significant difference in overall complication rates ( P  = 0.646). Of these, in the adenomyosis group, the most common complication was mild anemia (17.8%), followed by lung inflammation (9.6%), urinary tract infection (1.4%), and deep venous thrombosis (4.1%) whereas in the non-adenomyosis group, lung inflammation was the most frequently reported complication (14.3%), followed by mild anemia (7.9%), urinary tract infection (3.2%), and deep venous thrombosis (12.7%). Although a previous study suggested a higher risk of complications with adenomyosis [ 19 ], our study did not observe a significant difference between the two groups. While adenomyosis is commonly associated with anemia due to endometrial tissue within the uterine myometrium which leads to heavy menstrual bleeding, our findings suggest that these patients still experienced smoother postoperative recoveries. This highlights both the importance of expert surgical care and the potential for positive outcomes in endometrial cancer patients with adenomyosis.\nThe tumor histological findings, biochemical markers, and histochemical characteristics of the study population are detailed in Table  2 .\n Table 2 Tumor characteristics, histochemical marker, biochemical marker Adenomyosis (n = 73) (18.8%) No adenomyosis (n = 315) (81.2%) W/χ2 P -value Histology type χ2 = 0.412 0.521 Endometrioid 69(94.5) 291(92.4) Non-endometrioid 4(5.5) 24(7.6) Tumor grade χ2 = 2.389 0.303  I 49(67.1) 190(60.3)  II 19(26.0) 87(27.6)  III 5(6.8) 38(12.1) FIGO stage χ2 = 2.487 0.288  I 63(86.3) 248(78.7)  II 4(5.5) 30(9.5)  III 6(8.2) 37(11.7) Myometrial invasion χ2 = 2.769 0.096  < 1/2 66(90.4) 260(82.5)  > 1/2 7(9.6) 55(17.5) Cervical involvement χ2 = 1.133 0.287  Yes 6(8.2) 40(12.7)  No 67(91.8) 275(87.3) LVSI χ2 = 3.115 0.078  Yes 5(6.8) 46(14.6)  No 68(93.2) 269(85.4) LNM χ2 = 0.631 0.427  Yes 6(8.2) 36(11.4) Right Pelvic LNM 5 18 Left Pelvic LNM 0 5 Paraaortic LNM 0 6 Pelvic and Paraaortic LNM 1 7  No 67(91.8) 279(88.6) ER χ2 = 0.003 0.95  Positive 55(75.3) 226(71.7)  Negative 18(24.7) 89(28.3) PR χ2 = 0.060 0.806  Positive 54(74.0) 226(71.7)  Negative 19(26.0) 89(28.3)  p53 positive 46(63.0) 172(54.6) χ2 = 1.354 0.245  p16 positive 40(54.8) 138(43.8) χ2 = 2.131 0.144 Preoperative CA125 χ2 = 0.077 0.780  ≤ 35U/mL 56(76.7) 245(77.8)  > 35U/mL 17(23.3) 70(22.2) Endometrial Hyperplasia χ2 = 25.71  < 0.001  Yes 47(64.4) 102(32.4)  No 26(35.6) 213(67.6) Value are given as number (%) unless otherwise noted. Mann–Whitney U test (represented by W), chi-square test (χ2) LVSI  lympho-vascular space involvement,  LNM  lymph node metastasis,  ER  estrogen receptor,  PR  progesterone receptor,  Ca125  Cancer Antigen 125\nTumor characteristics, histochemical marker, biochemical marker\nValue are given as number (%) unless otherwise noted. Mann–Whitney U test (represented by W), chi-square test (χ2)\nLVSI  lympho-vascular space involvement,  LNM  lymph node metastasis,  ER  estrogen receptor,  PR  progesterone receptor,  Ca125  Cancer Antigen 125\nComparative analysis of histopathological parameters, including histological subtype, tumor grade, FIGO stage, depth of myometrial invasion, cervical involvement, lymphovascular space invasion (LVSI), and lymph node metastasis (LNM), revealed no statistically significant differences between the adenomyosis and non-adenomyosis groups. Histological subtypes ( P  = 0.521), tumor grade ( P  = 0.303), FIGO staging ( P  = 0.288), and LNM distribution ( P  = 0.427) were comparable. Depth of myometrial invasion approached statistical significance ( P  = 0.096), while cervical involvement ( P  = 0.287) and LVSI ( P  = 0.078) were not significantly different. Biochemical and molecular markers, including CA125 ( P  = 0.780), ER ( P  = 0.950), PR ( P  = 0.806), p53 ( P  = 0.245), and p16 ( P  = 0.144), also showed no significant differences. Notably, endometrial hyperplasia was significantly more prevalent in the adenomyosis group (64.4% vs. 32.4%,  P  < 0.001).\nThe cancer genome atlas molecular subtypes of EC showed in Table  3 . The 2023 Cancer Genome Atlas (TCGA) molecular classification system, which provides a more precise prognostic framework for endometrial cancer, was applied to a subset of patients. Due to its recent introduction, only 36 of 73 patients in the adenomyosis group and 165 of 315 in the non-adenomyosis group underwent molecular testing. The distribution of TCGA subtypes, including POLE-ultramutated (POLEmut), microsatellite-stable non-specific molecular profile (NSMP), mismatch repair-deficient (MMRd), and p53-mutated (p53), showed no significant differences between the two groups. However, The small sample size limits the statistical power and warrants prudent interpretation. Low testing rates in both groups may introduce selection bias, highlighting the need for larger, more comprehensive studies to validate these findings.\n Table 3 TCGA molecular subtypes of Endometrial cancer TCGA molecular subtypes Adenomyosis ( n  = 36) No Adenomyosis ( n  = 165) P -value POLE mutation 3(8.33) 20(12.12) 0.95 NSMP 22(61.11) 82(49.70) 0.95 MMR-d 8(22.22) 26(15.76) 0.82 p53abn 3(8.33) 37(22.42) 0.40 Value are given as number (%) unless otherwise noted TCGA  the cancer genome atlas,  NSMP  no specific molecular subtype,  MMR-d  mismatch repair defect\nTCGA molecular subtypes of Endometrial cancer\nValue are given as number (%) unless otherwise noted\nTCGA  the cancer genome atlas,  NSMP  no specific molecular subtype,  MMR-d  mismatch repair defect\n\nThe significance of the connection between adenomyosis and endometrial cancer, and its effect on prognosis, has been a topic of ongoing discussion [ 2 ,  5 ,  20 ,  21 ]. Adenomyosis, a common benign gynecologic condition with variable clinical symptoms, may influence the behavior and prognosis of EC [ 8 ]. The frequent coexistence of adenomyosis and endometrial cancer may be linked to shared risk factors or a common pathogenic process. There are three main theories that explain the development of adenomyosis: one suggests that it results from the invagination of endometrial tissue into the uterine muscle; another proposes that endometrial cells enter the myometrium via the lymphatic system; and the third theory suggests that adenomyosis may arise from de novo metaplasia, where ectopic endometrial tissue develops directly within the myometrium [ 22 ]. In our study, adenomyosis was present in 18.8% of patients who underwent hysterectomy for endometrial carcinoma. Importantly, this condition did not significantly influence on disease prognosis and patient survival.\nOur study analyzed the histopathological results of hysterectomy patients and found that endometrial hyperplasia was significantly more common in patients of EC with adenomyosis, occurring in 64.4% of cases, compared to 32.4% in those without adenomyosis ( P  < 0.001). This strong association suggests that coexistence of endometrial hyperplasia in adenomyosis may leads to endometrial cancer in these patients. A previous study similarly reported that (20.9%) of patients with adenomyosis had endometrial hyperplasia [ 2 ]. Other studies also found that the coexistence of adenomyosis and endometrial hyperplasia was more frequent than its association with endometrial cancer [ 22 ,  23 ]. Our finding are consistent with these reports. The higher prevalence of endometrial hyperplasia in EC patients with adenomyosis may be due to shared pathogenic mechanisms, though the exact process remains unclear [ 8 ,  11 ,  24 ]. Estrogen dominance plays a key role in the development of adenomyosis, endometrial hyperplasia and endometrial cancer [ 25 ]. Estrogen promotes the growth of adenomyosis and drives endometrial carcinogenesis by stimulating epithelial cell proliferation [ 26 ]. In addition to hormonal influences, other factors contribute to the coexistence of adenomyosis and EC. Genetic predisposition, including specific mutations or familial history, has been implicated in increasing susceptibility to both conditions [ 27 ,  28 ]. Chronic inflammation in adenomyosis fosters a pro-tumorigenic microenvironment, with inflammatory mediators driving cell proliferation, tissue remodeling, and malignant transformation [ 29 ]. Immune dysfunction, characterized by altered cytokine profiles and impaired surveillance, may facilitate the persistence of ectopic endometrial tissue and progression to cancer [ 15 ]. Additionally, growth factor pathways, such as epidermal growth factor (EGF) and fibroblast growth factors (FGFs), promote proliferation and angiogenesis [ 30 ], while oxidative stress, driven by reactive oxygen species (ROS), contributes to DNA damage and neoplastic changes [ 11 ]. These mechanisms underscore the complex pathogenesis linking adenomyosis and EC.\nIn our study, essential demographic factors such as age, parity, obesity, age at menarche and menopause, hypertension, and diabetes were analyzed for their potential association with EC prognosis. While comparing these factors between the two groups, we found that EC with coexisting adenomyosis was more frequently diagnosed in younger women compared to those with EC alone ( P  = 0.011). This finding is consistent with previous research reporting a higher prevalence of adenomyosis among younger EC patients [ 31 ]. This is likely due to earlier evaluations for adenomyosis symptoms like heavy bleeding and pain, which lead to incidental EC detection [ 32 ]. Moreover, adenomyosis is estrogen-dependent nature may also promote early malignant transformation [ 33 ]. Aditionally, adenomyosis-induced changes, including thickened myometrium and altered vascularity, may reduce tumor invasiveness, while increased surveillance in symptomatic patients supports early detection of less aggressive EC phenotypes [ 34 ]. Furthermore, our study showed that a lower proportion of patients in the adenomyosis group had reached menopause compared to the non-adenomyosis group (63.0% vs. 75.2%,  p  = 0.049), suggesting that adenomyosis is more common among perimenopausal women, which is consistent with previous reports [ 35 ]. These findings underscore the role of symptom-driven medical consultations in facilitating earlier detection, which may improve survival outcomes [ 36 ].\nFavorable prognostic factors for EC with adenomyosis, as identified in the literature, include the endometrioid type, low tumor grade, low FIGO stage, minimal myometrial invasion, and absence of LVSI or lymph node involvement. A study found adenomyosis to be linked to lower-grade tumors and minimal myometrial invasion [ 37 ]. Other research observed that EC with adenomyosis exhibited less aggressive characteristics and longer survival rates [ 38 ]. Additionally, it has been noted that EC patients with adenomyosis had a halved risk of death compared to those without adenomyosis [ 2 ]. These findings have led some researchers to suggest that the presence of adenomyosis in EC may be a positive prognostic factor [ 39 ].\nPossible explanations in the literature for the better prognosis in EC patients with adenomyosis include the hypothesis that adhesion between adenomyotic foci and cancer cells may prevent deep invasion [ 40 ], elevated antitumor cytokines and reduced oncogenic factors may limit tumor progression [ 23 ], and thickened endometrial stroma could act as a barrier to cancer invasion [ 11 ]. Additionally, symptoms such as dysmenorrhea and abnormal bleeding, commonly associated with adenomyosis, may lead to earlier diagnosis of EC [ 36 ]. But in several studies, existence of adenomyosis bring about deep myometrial invasion and LVSI [ 24 ,  41 ], possibly due to adenomyosis increasing myometrial infiltration and spread via lymph and veins, leading to higher lymphovascular space invasion in endometrial cancer [ 36 ]. However, our study showed that EC patients with adenomyosis did not benefit from it. Perhaps it is related to well-established diagnostic and treatment techniques, or perhaps continuing to expand the number of samples included will reveal a difference.\nSimilar to a study [ 14 ], our research showed higher ER and PR expression in the adenomyosis group compared to the non-adenomyosis group, though the differences were not statistically significant (ER: 75.3% vs. 71.7%,  p  = 0.95; PR: 74.0% vs. 71.7%,  p  = 0.806). In our study, which covers patients from 2019 to 2023, the FIGO 2009 system was applied for staging. However, the FIGO endometrial cancer staging system was revised to reflect new clinical evidence obtained since the 2009 guidelines recently [ 42 ]. Implementing the FIGO 2023 endometrial cancer staging system in clinical practice will enhance the thoroughness of preoperative assessments for women diagnosed with endometrial cancer which includes the various histological types, tumor patterns and molecular classification [ 42 ]. So we re-staged these patients using FIGO 2023 and found there is also no statistical difference in the adenomyosis group compared to the non-adenomyosis group ( P  > 0.05). Molecular classification systems have greatly improved endometrial cancer diagnosis and treatment over the past decade [ 43 ]. To enhance accuracy, TCGA molecular classification categorizes these cancers into these four types: POLE mutation, MMR-d, NSMP, and p53abn. This classification streamlines risk stratification and is now part of the FIGO 2023 staging system [ 44 ]. The 2023 FIGO staging system categorizes endometrial cancers into aggressive (high-grade endometrial cancers, including FIGO grade 3 endometrioid endometrial carcinomas (EEC) and all Non-EECs such as serous, clear cell, mixed and mucinous) and non-aggressive histologic types (low-grade or FIGO grade 1–2 EECs) based on their aggressiveness [ 45 ]. These tumors are further classified into above maintained four categories by TCGA molecular classification. In our study, the analysis did not find a significant difference between patients with and without adenomyosis. A study similarly found that the prevalence of P53abn and MMR-d does not differ between endometrial cancer patients with and without coexistent adenomyosis [ 46 ]. Larger studies are needed to confirm these findings and to better understand the molecular characteristics of endometrial cancer in the context of adenomyosis.\nAll patients in this study underwent minimally invasive surgery (MIS), including laparoscopy and robotic-assisted procedures, which are now standard for endometrial cancer management [ 47 ]. MIS offers significant advantages over laparotomy, with studies reporting reduced surgical morbidity, shorter recovery times, and improved outcomes [ 48 – 50 ]. Although one study did not show a significant difference in overall survival between MIS and open surgery [ 48 ], MIS is generally associated with superior survival outcomes in early-stage endometrial cancer per NCCN guidelines [ 50 – 52 ]. Despite its benefits, MIS remains invasive and poses risks such as postoperative pulmonary complications and venous thromboembolism (VTE), primarily due to carbon dioxide pneumoperitoneum, the Trendelenburg position, and extended operative times [ 53 ,  54 ]. In our cohort, the most frequent complications were pulmonary inflammation, VTE, and anemia, with no statistically significant differences in postoperative complication rates between patients with and without adenomyosis.\nOur study found a reduced need for adjuvant therapy in EC patients with adenomyosis (21.9% vs. 37.8%,  P  = 0.015). Similar findings were reported in a study, which also demonstrated that patients with adenomyosis required less adjuvant therapy compared to those without adenomyosis [ 55 ]. Since EC treatment is primarily surgical, the decision for adjuvant therapy relies on surgical staging and key clinicopathological risk factors [ 56 ]. Adenomyosis may also influence the biology of EC, potentially making it less aggressive and, therefore, less likely to require adjuvant therapy. It is often linked to lower-risk features, such as earlier tumor stage, minimal myometrial invasion, and reduced incidences of LNM and LVSI. According to Gynecologic Oncology Group (GOG) criteria, these patients typically fall into the low or low-intermediate risk category, where surgery alone is sufficient without further adjuvant treatment [ 3 ]. Furthermore, guidelines from the European Society for Medical Oncology (ESMO), the European Society of Gynaecological Oncology (ESGO), and the European Society for Radiotherapy and Oncology (ESTRO) further support these observations [ 57 ]. Patients in the low-risk category (stage IA, grade 1–2, endometrioid histology, no LVSI) do not require adjuvant treatment, while those in intermediate and high-intermediate risk groups are considered for therapy based on additional factors like age [ 57 ,  58 ]. Adenomyosis, by limiting tumor aggressiveness, places most patients within the low-risk spectrum, reducing the need for further treatment. These findings highlight the need for personalized treatment in EC patients with adenomyosis. Accurate surgical staging and pathological evaluation are crucial, as avoiding unnecessary adjuvant therapy can minimize treatment-related toxicities while maintaining effective outcomes. Further research is needed to incorporate adenomyosis into risk stratification models for better therapeutic decision-making.\nThe strength of our study lies in its comprehensive clinical and histopathological analysis of endometrial cancer in patients with and without adenomyosis with a large sample size and a relatively long median follow-up period. Our use of updated staging and molecular classification systems ensures the relevance and precision of the results, aligning them with current clinical practices. Notably, the study’s novel focus on postoperative complications in the context of adenomyosis offers unique insights not previously explored in the literature, making a significant contribution to the field. This study has certain limitations. The TCGA molecular classification, introduced in 2023, was performed on a subset of patients due to its recent implementation and limited availability, potentially introducing bias related to the smaller sample size. DFS data were limited by the low number of recurrence events, and no multivariate Cox regression analysis could be performed. This limitation restricts the interpretation of DFS outcomes in terms of their independent association with adenomyosis. Additionally, the retrospective design of the study is inherently prone to selection and information biases, which may affect the reliability of the findings. Future prospective studies with larger and more representative cohorts are warranted to validate these results and overcome these limitations.\n\nThis study demonstrates that adenomyosis does not significantly impact tumor progression or survival outcomes suggesting a neutral role in endometrial cancer prognosis. Adenomyosis patients are younger with a lower incidence of menopause and show reduced utilization of adjuvant therapy, potentially reflecting differences in disease biology. Notably, the higher prevalence of endometrial hyperplasia in the adenomyosis cohort suggests a potential link between adenomyosis and hyperplastic changes, which may contribute to the pathogenesis of endometrial cancer. These findings imply that adenomyosis may be an incidental co-occurrence rather than a biological driver of endometrial cancer.\n\nSupplementary Material 1: Figure S1. Kaplan–Meier survival curve compares overall survival probabilities between patients with adenomyosis (red line) and without adenomyosis (blue line) over a follow-up period of up to 60 months. The survival curves are nearly identical, with a log-rank test  p -value of 0.66, indicating no statistically significant difference in survival outcomes between the two groups.\nSupplementary Material 1: Figure S1. Kaplan–Meier survival curve compares overall survival probabilities between patients with adenomyosis (red line) and without adenomyosis (blue line) over a follow-up period of up to 60 months. The survival curves are nearly identical, with a log-rank test  p -value of 0.66, indicating no statistically significant difference in survival outcomes between the two groups.","source_license":"CC0","license_restricted":false}