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1

Aoki, Yoichi, Hiroyuki Kanao, Xipeng Wang, Mayu Yunokawa, Kohei Omatsu, Atsushi Fusegi, and Nobuhiro Takeshima. "Adjuvant treatment of endometrial cancer today." Japanese Journal of Clinical Oncology 50, no. 7 (May 28, 2020): 753–65. http://dx.doi.org/10.1093/jjco/hyaa071.

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Abstract Endometrial cancer frequently occurs in post-menopausal women, and the endometrium is a well-known site of cancer affecting women. Endometrial cancer is found with genital bleeding and often at an early stage. However, there are some risks of recurrence after hysterectomy. As a medical treatment after the diagnosis of endometrial cancer, appropriate adjuvant therapy is considered to lead to a decrease in the rate of recurrence and improvement of prognosis according to the determination of the cancer stage from the surgical and histopathological results. In this review, we describe post-operative adjuvant therapy administered for endometrial cancer and advanced disease, focusing on chemotherapy, radiation therapy and the combination of both. These treatments are divided according to the risk of recurrence as based primarily on the reported evidence.
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DeLeon, Maria C., Natraj R. Ammakkanavar, and Daniela Matei. "Adjuvant therapy for endometrial cancer." Journal of Gynecologic Oncology 25, no. 2 (2014): 136. http://dx.doi.org/10.3802/jgo.2014.25.2.136.

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3

Hogberg, Thomas. "Adjuvant Chemotherapy in Endometrial Cancer." International Journal of Gynecologic Cancer 20, Suppl 2 (September 2010): S57—S59. http://dx.doi.org/10.1111/igc.0b013e3181f749fd.

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The indications for adjuvant therapy in endometrial cancer are briefly reviewed. The importance of systemic adjuvant therapy is emphasized. A short summary of randomized studies on adjuvant chemotherapy versus radiotherapy and on adjuvant sequential chemotherapy plus radiotherapy versus radiotherapy alone is given. On the basis of the present results from randomized trials, a combination of adjuvant radiotherapy and platinum-based chemotherapy seems to be most effective.
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4

Gerasimov, Aleksey V., Sergey E. Krasilnikov, Anna G. Kedrova, Tatyana A. Maksimenko, Nataliya S. Afonina, Olga E. Nechaeva, and Valentine V. Kosyi. "Morphological and ultrasound characteristics of endometrium in patients with breast cancer and the risk of secondary tumors." Journal of Clinical Practice 6, no. 4 (November 15, 2015): 39–47. http://dx.doi.org/10.17816/clinpract83249.

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The analysis of features of endometrial hyperplasia in patients with breast cancer (BC) receiving adjuvant tamoxifen therapy in the period from 2011 to 2014 inclusive. 196 patients with breast cancer with ultrasound criteria of endometrial hyperplasia were examined. A postoperative histopathologic examination revealed that the lesions were endometrial hyperplasias and with 4,1% malignant findings. Hyperplasia, polyps and endometrial cancer were diagnosed in patients receiving tamoxifen, which allowed a comparison clinicoanamnestic, ultrasound, morphological and genetic characteristics of the endometrium to recover a high risk of developing a second cancer, as well as offer a pathogenic variant of its prevention. The article can be interesting as for obstetrician-gynecologist, watching women after breast cancer treatment, and oncologists, choosing a drug for adjuvant therapy.
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5

Gerasimov, A. V., S. E. Krasilnikov, A. G. Kedrova, N. S. Afonina, O. E. Nechaeva, T. A. Maksimenko, and V. V. Kosyi. "MORPHOLOGICAL AND ULTRASOUND CHARACTERISTICS OF ENDOMETRIUM IN PATIENTS WITH BREAST CANCER AND THE RISK OF SECONDARY TUMORS." Journal of Clinical Practice 6, no. 3 (September 15, 2015): 39–47. http://dx.doi.org/10.17816/clinpract6339-47.

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The analysis of features of endometrial hyperplasia in patients with breast cancer (BC) receiving adjuvant tamoxifen therapy in the period from 2011 to 2014 inclusive. 196 patients with breast cancer with ultrasound criteria of endometrial hyperplasia were examined. A postoperative histopathologic examination revealed that the lesions were endometrial hyperplasias and with 4,1% malignant findings. Hyperplasia, polyps and endometrial cancer were diagnosed in patients receiving tamoxifen, which allowed a comparison clinicoanamnestic, ultrasound, morphological and genetic characteristics of the endometrium to recover a high risk of developing a second cancer, as well as offer a pathogenic variant of its prevention. The article can be interesting as for obstetrician-gynecologist, watching women after breast cancer treatment, and oncologists, choosing a drug for adjuvant therapy.
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6

Nama, Vivek, Amit Patel, Lisa Kirk, John Murdoch, and Joanne Bailey. "Role of Systematic Lymphadenectomy to Tailor Adjuvant Therapy in Early Endometrial Cancer." International Journal of Gynecologic Cancer 28, no. 1 (January 2018): 107–13. http://dx.doi.org/10.1097/igc.0000000000001148.

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ObjectiveThe long-standing protocol at our center for apparent stage I and II endometrial cancers comprises hysterectomy and bilateral salpingo-oophorectomy without lymphadenectomy. Adjuvant treatment is based in line with Postoperative Radiation Therapy in Endometrial Carcinoma 1 protocol. Our aim was to quantify the number of patients who would avoid external beam radiation therapy (EBRT) in our institution if we adopted a protocol of lymphadenectomy to tailor adjuvant EBRT and its impact on cost and quality of life.DesignRetrospective case-cohort study.SettingGynecological oncology center.MethodsAll endometrial cancers treated from 2007 to 2012 were included. The European Organization for Research and Treatment of Cancer (EORTC) quality of life (QLQ-30) and endometrial cancer specific (EN-24) questionnaires were used to measure the quality of life. The NHS tariff for EBRT, VBT and lymphadenectomy were obtained from our Trust’s contract with the local commissioning groups.Main Outcome MeasuresQuality of life and cost.ResultsSystematic pelvic lymphadenectomy in early endometrial cancers of all grades would avoid EBRT in 23.3% of patients, and if performed for grade 2 and 3 cancers, 39.5% of patients would avoid EBRT. The global health scores were significantly lower, and pain scores were considerably higher in patients who received EBRT. Performing systematic lymphadenectomy and tailored adjuvant therapy in grade 2 and 3 endometrial cancers would save £134,691 and for all grades save £37,161 for every 100 patients treated with early endometrial cancer.ConclusionSystematic lymphadenectomy with tailored adjuvant therapy may offer better QoL with reduced cost to NHS without a reduction in overall survival.
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7

Kumar, Piyush, and Jai Kishan Goel. "Cancer Endometrium: An Update." Journal of South Asian Federation of Obstetrics and Gynaecology 4, no. 2 (2012): 75–84. http://dx.doi.org/10.5005/jp-journals-10006-1179.

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ABSTRACT Endometrial cancer is the most common gynecological cancer in developed countries and second most common in developing countries. Its incidence is increasing in postmenopausal women. Factors related to chronic estrogen exposure are associated with a higher incidence. Abnormal uterine bleeding is the cardinal symptom. All women with suspected endometrial cancer require transvaginal ultrasonography and most will undergo endometrial biopsy; more sophisticated radiological examinations are required for preoperative staging. The general approach for treatment of endometrial cancer is hysterectomy, bilateral salpingo-oophorectomy, abdominopelvic washings, lymph node evaluation and maximal surgical cytoreduction for those with advanced disease. Postoperative adjuvant therapy [vaginal brachytherapy, external beam radiation therapy (RT), chemotherapy] may be recommended depending on the estimated risk of recurrence. Individual patient characteristics and surgical as well as pathologic staging are the main factors that are used for postsurgical risk stratification, which in turn, directs the selection of adjuvant treatment. How to cite this article Goel JK, Kumar P. Cancer Endometrium: An Update. J South Asian Feder Obst Gynae 2012;4(2):75-84.
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8

Hsiao, Sheng-Mou, and Lin-Hung Wei. "Controversies in the Adjuvant Therapy of Endometrial Cancer." ISRN Obstetrics and Gynecology 2011 (September 29, 2011): 1–4. http://dx.doi.org/10.5402/2011/724649.

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Endometrial cancer is the most common malignancy of the female genital tract. Surgical treatment includes hysterectomy, bilateral salpingo-oophorectomy, and an appropriate staging procedure. Relapse of endometrial cancer may occur in patients with high risk factors, such as old age, grade 3 cancer, deep myometrial invasion, and papillary serous and clear cell types. In recent years, several randomized trials reported the results of adjuvant therapy for patients with high risk factors. Nonetheless, some controversies still exist. This paper presents and discusses the results of important randomized trials of adjuvant therapy for endometrial cancer with risk factors.
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9

Kuku, Stephanie, Matt Williams, and Mary McCormack. "Adjuvant Therapy in Stage III Endometrial Cancer." International Journal of Gynecological Cancer 23, no. 6 (July 2013): 1056–64. http://dx.doi.org/10.1097/igc.0b013e3182978328.

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10

Luo, Leo, Weiji Shi, Zhigang Zhang, and C. Jillian Tsai. "Association of delayed adjuvant therapy and overall survival in early stage endometrial cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 5590. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.5590.

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5590 Background: The primary treatment for early stage endometrial cancer includes definitive surgical staging procedure followed by adjuvant therapy in women with high risk of recurrence. The optimal interval time between surgery and adjuvant therapy is unclear. Methods: 349,404 patients with primary uterine carcinoma diagnosed from 2004 and 2012 were extracted from National Cancer Database (NCDB). Study population was limited to patients with FIGO 2009 stage I and II endometrial cancer with endometroid, mucinous, clear cell, or serous histology. Adjuvant therapy included radiation therapy, chemotherapy, or a combination. A binary variable of interval time between surgery and adjuvant therapy (“early” vs. “delayed”) was created by using the median time as a cutoff. Analysis of relationship between the interval time and overall survival was performed. Results: Final analysis included 118,373 early stage endometrial cancer patients who had definitive surgical treatment. Median age was 61 (interquartile range 55-69). 87,189 patients (74%) had stage IA disease, 21,573 (18%) patients had stage IB disease, and 9,611 (8%) patients had stage II disease. 28,824 (24%) patients received adjuvant therapy after surgery. The median time from surgery to adjuvant therapy was 1.6 months (interquartile range 1.3-2.2 months). Of the patients that received adjuvant therapy, 48% received intra-vaginal brachytherapy alone, 31% received pelvic external beam radiation, and 7% received a combination of chemotherapy and brachytherapy. There was a significant difference in overall survival in patients who received adjuvant therapy within 1.6 months from surgery and 1.6 months after surgery (Log-rank test, p = 0.04). Patients with advanced age, African-American or Hispanic race, and uninsured status or government-sponsored insurance were associated with delayed treatments. Conclusions: In this large retrospective review of early stage endometrial cancer patients, delayed time between surgery and adjuvant therapy is associated with worse overall survival. Further analysis will be performed to determine an optimal timing between surgery and adjuvant therapy.
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11

Loibl, S., G. von Minckwitz, and M. Kaufmann. "Adjuvant hormone therapy following primary therapy for endometrial cancer." European Journal of Cancer 38 (September 2002): 41–43. http://dx.doi.org/10.1016/s0959-8049(02)00281-2.

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12

Giustozzi, Alessandra, Vanda Salutari, Elena Giudice, Lucia Musacchio, Caterina Ricci, Chiara Landolfo, Maria Teresa Perri, Giovanni Scambia, and Domenica Lorusso. "Refining Adjuvant Therapy for Endometrial Cancer: New Standards and Perspectives." Biology 10, no. 9 (August 30, 2021): 845. http://dx.doi.org/10.3390/biology10090845.

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Endometrial carcinoma is the most frequent cancer of the reproductive female organs. Most endometrial cancers are diagnosed at early stage (75%). Treatment options depend on pathogenetic, histopathologic and clinical characteristic at the diagnosis. To improve patient management in the near future, recent research has focused on new molecular features; evidence has shown that these give a better definition of patient prognosis and can help in tailoring adjuvant treatments by identifying specific subgroups of patients whose tumors may benefit from specific therapeutic approaches. In this review, we will focus on current knowledge of adjuvant treatment of endometrial carcinoma, using a prognostic-risk group stratification based on pathogenetic, clinical and molecular features, and will take a look at the ongoing trials that will further change the therapeutic approach in coming years.
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13

Bogani, Giorgio, Serena Cappuccio, Jvan Casarin, Deepa Maheswari M. Narasimhulu, William A. Cilby, Gretchen E. Glaser, Amy L. Weaver, et al. "Role of adjuvant therapy in stage IIIC2 endometrial cancer." International Journal of Gynecologic Cancer 30, no. 8 (July 9, 2020): 1169–76. http://dx.doi.org/10.1136/ijgc-2020-001446.

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ObjectiveThe role of the different types of adjuvant treatments in endometrial cancer with para-aortic node metastases is unclear. The aim of this study was to report oncologic outcomes after adjuvant therapy in patients with stage IIIC2 endometrial cancer.MethodsThis retrospective single-institution study assessed patients with stage IIIC2 endometrial cancer who underwent primary surgery from January 1984 to December 2014. All patients had hysterectomy (±salpingo-oophorectomy) plus lymphadenectomy (para-aortic nodes, ±pelvic nodes). We included all patients with stage III endometrial cancer and documented para-aortic lymph node metastases (International Federation of Obstetrics and Gynecologists stage IIIC2). We excluded patients who did not provide consent, who had synchronous cancer, or who underwent neoadjuvant chemotherapy. Follow-up was restricted to the first 5 years post-operatively. Cox proportional hazards models, with age as the time scale, was used to evaluate associations of risk factors with disease-free survival and overall survival.ResultsAmong 105 patients with documented adjuvant therapy, external beam radiotherapy was administered to 25 patients (24%), chemotherapy to 24 (23%), and a combination (chemotherapy and external beam radiotherapy) to 56 (53%) patients. Most patients receiving chemotherapy and external beam radiotherapy (80%) had chemotherapy first. The majority of relapses had a distant component (31/46, 67%) and only one patient had an isolated para-aortic recurrence. Non-endometrioid subtypes had poorer disease-free survival (HR 2.57; 95% CI 1.38 to 4.78) and poorer overall survival (HR 2.00; 95% CI 1.09 to 3.65) compared with endometrioid. Among patients with endometrioid histology (n=60), chemotherapy and external beam radiotherapy improved disease-free survival (HR 0.22; 95% CI 0.07 to 0.71) and overall survival (HR 0.28; 95% CI 0.09 to 0.89) compared with chemotherapy or external beam radiotherapy alone. Combination therapy did not improve prognosis for patients with non-endometrioid histology (n=45).ConclusionsIn our cohort of patients with stage IIIC2 endometrioid endometrial cancer, those receiving chemotherapy and external beam radiotherapy had improved survival compared with patients receiving chemotherapy or external beam radiotherapy alone. However, the prognosis of patients with non-endometrioid endometrial cancer remained poor, regardless of the adjuvant therapy administered. Distant recurrences were the most common sites of failure.
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14

Tangjitgamol, Siriwan, Jakkapan Khunnarong, Kanyarat Katanyoo, Sunamchok Srijaipracharoen, Thaovalai Thavaramara, and Kamol Pataradool. "Patterns of Adjuvant Therapy for Endometrial Cancer: Single Institutional Experience in Thailand." International Journal of Gynecologic Cancer 25, no. 4 (May 2015): 665–72. http://dx.doi.org/10.1097/igc.0000000000000391.

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AimThe aim of this study was to evaluate the use of adjuvant therapy and treatment outcomes in patients with endometrial cancer (EMC).MethodsPatients with EMC treated in the institution were identified. Data collected were age, stage of disease, histopathology, and adjuvant therapy. Progression-free survival (PFS) and overall survival (OS) were studied.ResultsThe median age of 383 patients was 57 years (30–86 years). Majority had early-stage diseases (76.5%), endometrioid histopathology (87.2%), and high-grade tumors (74.9%). Less than half (44.4%) had adjuvant therapy. Pelvic radiation was the most common type of adjuvant treatment. We found that 25.7% of stages III to IV patients did not have adjuvant therapy (mainly from old age or poor performance status). On the other hand, 21.5% of patients with stage IA had adjuvant treatment (owing to risk factors or other synchronous cancers). The 5-year PFS and 5-year OS (95% confidence interval) were 84.3% (80.5%–88.1%) and 81.2% (77.1%–85.4%), respectively. Significant prognostic factors for survival by univariable analyses were stage, tumor grade, and histopathology. By multivariable analyses, significant prognostic factors were stage, tumor grade (only for OS), histopathology, and adjuvant therapy. Focusing on stage and adjuvant therapy, we found that the PFS and OS of early-stage patients who had or did not have adjuvant therapy were not significantly different, whereas the PFS and OS of advanced-stage patients who had adjuvant treatment were significantly higher than the PFS and OS of those who did not have adjuvant treatment.ConclusionsThe use of adjuvant therapy for patients with EMC was not according to the standard recommendation in all patients for many reasons. The benefit of adjuvant therapy was demonstrated in advanced- but not in early-stage cancer.
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Moberger, B., T. Fornander, and A.-C. HellstrÖM. "DNA-content in endometrial carcinoma of tamoxifen-treated breast cancer patients." International Journal of Gynecologic Cancer 4, no. 2 (1994): 131–34. http://dx.doi.org/10.1046/j.1525-1438.1994.04020131.x.

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DNA measurements and histopathologic evaluation were performed in 17 patients treated with adjuvant tamoxifen for early breast cancer and who developed endometrial carcinoma during or after the tamoxifen therapy. The tumors were exclusively characterized by euploid DNA content except for two cases, one mixed mesodermal sarcoma, a highly malignant and rare tumor, and one adenocarcinoma. Although the use of adjuvant tamoxifen therapy most likely enhances the risk of developing endometrial carcinoma, the beneficial effects of adjuvant breast cancer treatment is of well-known clinical importance. The hazards of giving long-term tamoxifen seem to be low since the endometrial tumors were associated with low-grade malignancy and euploid DNA pattern.
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Emons, Günther, Clemens Tempfer, Marco Battista, Alexander Mustea, and Dirk Vordermark. "Statement of the Uterus Committee of the Gynaecological Oncology Working Group (AGO) on the PORTEC-3 study." Geburtshilfe und Frauenheilkunde 78, no. 10 (October 2018): 923–26. http://dx.doi.org/10.1055/a-0658-1918.

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AbstractThe data on the adjuvant therapy of endometrial cancer (EC) are inconsistent. Recent studies of this topic such as PORTEC-3, GOG-258 and GOG-249 investigated the value of adjuvant radiotherapy, adjuvant chemotherapy and combined adjuvant chemoradiotherapy followed by chemotherapy in patients with endometrial cancer and an increased risk of recurrence. With this statement, the Uterus Committee of the Gynaecological Oncology Working Group (AGO) wishes therefore to interpret the new data and discuss them against the background of the new S3 guideline “Diagnosis, treatment and follow-up of patients with endometrial cancer”.
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17

Kupets, Rachel, Tien Le, Tien Le, James Bentley, Scott Farrell, Michel P. Fortier, Christopher Giede, et al. "The Role of Adjuvant Therapy in Endometrial Cancer." Journal of Obstetrics and Gynaecology Canada 35, no. 4 (April 2013): 375–76. http://dx.doi.org/10.1016/s1701-2163(15)30968-3.

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18

Stearns, V., and E. P. Gelmann. "Does tamoxifen cause cancer in humans?" Journal of Clinical Oncology 16, no. 2 (February 1998): 779–92. http://dx.doi.org/10.1200/jco.1998.16.2.779.

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PURPOSE To review the preclinical and clinical data on the carcinogenic potential of tamoxifen. DESIGN A MEDLINE search on the carcinogenicity of tamoxifen was conducted and the literature reviewed. RESULTS Because tamoxifen has estrogen-like effects on some tissues, such as the human uterus, there has been concern that tamoxifen could promote endometrial cancers in women on chronic tamoxifen therapy. Observations in some randomized trials of adjuvant tamoxifen therapy are consistent with a small, but real, increased risk of endometrial cancer in women who take tamoxifen. Since increased endometrial cancer incidence has not been observed in all studies of chronic tamoxifen therapy, there may be an element of detection bias. Laboratory studies have demonstrated that tamoxifen is hepatocarcinogenic in laboratory rats, but not in other species. This carcinogenicity in rats has been linked to the formation of DNA adducts. CONCLUSION The incidence of endometrial cancer is increased in women who take tamoxifen. The data suggest that tamoxifen might be a tumor promoter in human endometrium. However, on the basis of the number of tumors seen by endometrial sampling of tamoxifen-treated women, the impact of tamoxifen as a tumor promoter is small. Women on chronic tamoxifen therapy should have routine annual gynecologic examinations and receive endometrial sampling only in the event of uterine bleeding. Unlike the data in rats, there is no conclusive evidence to link tamoxifen with an increased rate of hepatocellular cancer in humans; the contrasting carcinogenic potential may be attributed to substantial interspecies differences in the metabolism of tamoxifen.
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19

Tangjitgamol, S., S. Manusirivithaya, and C. Lertbutsayanukul. "Adjuvant therapy for early-stage endometrial cancer: a review." International Journal of Gynecologic Cancer 17, no. 5 (September 2007): 949–56. http://dx.doi.org/10.1111/j.1525-1438.2007.00860.x.

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Most patients with endometrial cancer (EMC) present their symptoms early in their course, leading to an overall favorable outcome. However, some patients who are in early-stage diseases may carry some risk features that would hamper their prognoses. For these early-stage diseases with high risk of recurrences, radiation therapy certainly plays a major role as an adjuvant treatment. Despite an excellent local diseases control by radiation, systemic failures are still encountered. To improve the prognoses, other types of adjuvant therapy have been attempted. In this review, various options of adjuvant treatment for this early-stage EMC including radiation therapy, chemotherapy, and hormonal therapy are discussed.
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20

Hogberg, Thomas. "Chemotherapy for Early-stage High-risk Endometrial Cancer." European Oncology & Haematology 05, no. 01 (2009): 71. http://dx.doi.org/10.17925/eoh.2009.05.1.71.

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Endometrial cancer generally has a good prognosis because most cases are diagnosed in stage I. It is possible to identify subgroups of patients with early-stage endometrial cancer with a poor prognosis. Despite a traditional generous use of adjuvant radiotherapy, these patients have five-year overall survival of approximately 80%. In this group there is a need for an effective systemic adjuvant therapy. Mainly based on superior response rates, doxorubicin + cisplatin was for many years the standard chemotherapy in endometrial cancer. Gynecologic Oncology Group (GOG)-177 was the first phase III study on chemotherapy in endometrial cancer that showed a survival advantage. Paclitaxel + doxorubicine + cisplatin was better than doxorubicine + cisplatin, but the toxicity of the three-drug regimen has precluded general acceptance. Paclitaxel + carboplatin has produced high response rates and is widely used, despite the lack of evidence based on randomised studies. GOG-122 compared doxorubicine + cisplatin with whole abdominal radiotherapy in advanced optimally operated endometrial cancer and showed that chemotherapy with doxorubicine + cisplatin resulted in superior survival. Two recent studies have compared adjuvant chemotherapy (cyclophosphamide + doxorubicine + cisplatin) with adjuvant radiotherapy in early-stage endometrial cancer. Both studies failed to show a difference between the treatments. Another study (NSGO-EC-9501/EORTC-55991) compared adjuvant radiotherapy plus chemotherapy with adjuvant radiotherapy, and showed better survival with the sequential combination.
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Roh, Young Ho, and Sung Yob Kim. "The role of Adjuvant Radiation therapy in Endometrial carcinoma." Journal of Medicine and Life Science 6, no. 1 (December 1, 2007): 13–20. http://dx.doi.org/10.22730/jmls.2008.6.1.13.

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Endometrial cancer is a third common gynecologic malignancy in Korea, affecting approximately 714 women per year. Despite the publication of several prospective randomized trials, there continues to be controversy regarding the use of adjuvant radiation therapy in endometrial cancer management. It is clear that most women with early stage, low-risk disease will do well without adjuvant therapy. Intermediate-risk patients are at risk for local regional relapse, and radiotherapy has been shown to effectively reduce this risk without significantly impacting overall survival. The absence of a clear impact on survival has resulted in a lack of consensus regarding the use of radiotherapy in intermediate-risk patients. At the same time, the patterns of failure in intermediate-risk patients have resulted in differing recommendations regarding appropriate radiotherapy targets. High-risk patients are also at risk for local failure, and targeted radiotherapy may be appropriate. In this article, we discuss the controversies surrounding the role of adjuvant radiotherapy in endometrial cancer using an evidence-based approach.
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Evrard, Camille, and Jérôme Alexandre. "Predictive and Prognostic Value of Microsatellite Instability in Gynecologic Cancer (Endometrial and Ovarian)." Cancers 13, no. 10 (May 18, 2021): 2434. http://dx.doi.org/10.3390/cancers13102434.

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For endometrial cancer, a new classification is now available from ESMO, ESGO, and ESTRO based on clinical and molecular characteristics to determine adjuvant therapy. The contribution of molecular biology is major for this pathology mainly by the intermediary of deficient mismatch repair/microsatellite instability. Detection techniques for this phenotype have many peculiarities in gynecologic cancers (endometrial and ovarian) because it has been initially validated in colorectal cancer only. Endometrial cancer is the most common tumor with deficient mismatch repair, which is an important prognostic factor and a predictor of the benefit of adjuvant treatments. Concerning advanced stages, this phenotype is a theragnostic marker for using immunotherapy. Among ovarian cancer, microsatellite instability is less described in literature but exists, particularly in endometrioid type ovarian cancer. This review aims to provide an overview of the publications concerning deficient mismatch repair/microsatellite instability in endometrial and ovarian cancers, detection techniques, and clinical implications of these molecular characteristics.
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Ryu, Ki-Jin, Min Sun Kim, Ji Yoon Lee, Seunghyun Nam, Hye Gyeong Jeong, Tak Kim, and Hyuntae Park. "Risk of Endometrial Polyps, Hyperplasia, Carcinoma, and Uterine Cancer After Tamoxifen Treatment in Premenopausal Women With Breast Cancer." JAMA Network Open 5, no. 11 (November 28, 2022): e2243951. http://dx.doi.org/10.1001/jamanetworkopen.2022.43951.

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ImportanceThe association of tamoxifen use with the risk of uterine diseases, such as endometrial cancer, in premenopausal women with breast cancer remains controversial. However, many studies have reported an increased risk of uterine disease among postmenopausal tamoxifen users.ObjectiveTo investigate the association of tamoxifen use with the risk of endometrial cancer and other uterine diseases in premenopausal women with breast cancer.Design, Setting, and ParticipantsA nationwide, population-based, retrospective longitudinal cohort study with an 18-year study period was conducted using data obtained from the Korean National Health Insurance Service. Participants included premenopausal women aged 20 to 50 years with breast cancer diagnoses between January 2003 and December 2018. Data were analyzed from April to December 2021.ExposuresTamoxifen treatment.Main Outcomes and MeasuresThe incidence of uterine diseases, including endometrial cancer, hyperplasia, polyps, and other uterine cancers, was identified in the study cohort using insurance claim codes. The incidence of uterine diseases per 1000 person-years was compared between women receiving tamoxifen and those not treated with adjuvant hormone therapy. Multivariable Cox proportional hazard regression analysis was performed to determine the risk of each uterine disease.ResultsAmong 78 320 female participants with a mean (SD) age of 42.1 (6.1) years, 34 637 (44.2%) were categorized into the tamoxifen group and 43 683 (55.8%) were categorized into the control group. Among tamoxifen users, during the mean (SD) follow-up duration of 6.13 (4.15) years, the incidence of newly diagnosed endometrial polyps was 20.13 cases per 1000 person-years, that of endometrial hyperplasia was 13.49 cases per 1000 person-years, that of endometrial cancer was 2.01 cases per 1000 person-years, and that of other uterine cancers was 0.45 cases per 1000 person-years. The risk of endometrial cancer was higher in the tamoxifen group than in the control group (hazard ratio, 3.77; 95% CI, 3.04-4.66) after adjusting for age, body mass index, history of diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, gonadotropin-releasing hormone agonist treatment, and trastuzumab treatment.Conclusions and RelevanceIn this longitudinal cohort study, premenopausal Korean women with breast cancer who received tamoxifen as adjuvant hormone therapy had a significantly increased risk of endometrial hyperplasia, polyps, carcinoma, and other uterine cancers compared with those who were not treated with adjuvant hormone therapy. These findings suggest that clinicians should consider the risk of uterine disease among tamoxifen users, including premenopausal women.
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Cecchini, Silvia, Stefano Ciatto, Rita Bonardi, Antonia Mazzotta, Paolo Pacini, Maria Grazia Muraca, and Marco Zappa. "Risk of Endometrial Cancer in Breast Cancer Patients under Long-Term Adjuvant Treatment with Tamoxifen." Tumori Journal 84, no. 1 (January 1998): 21–23. http://dx.doi.org/10.1177/030089169808400104.

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Aims To evaluate the relative risk of endometrial cancer with respect to the expected underlying incidence in breast cancer patients undergoing long-term adjuvant tamoxifen therapy. Methods A total of 1010 postmenopausal breast cancer patients receiving adjuvant tamoxifen and with a first negative endometrial ultrasonography (cutoff for abnormal endometrial thickness >5 mm) were followed by annual transvaginal ultrasonography. Abnormal endometrial thickness prompted an outpatient endometrial biopsy or curettage under anesthesia in the case of cervical stenosis and increasing endometrial thickness. The standardized incidence ratio (SIR) with respect to underlying incidence was determined. Results A total of 1,010 eligible subjects who had been receiving tamoxifen for an average of 51 months were enrolled and followed for a total of 2,361 patient-years between January 1993 and December 1996. Five cases of endometrial cancer were observed in the study period: 1 was detected at screening, and 4 were diagnosed for vaginal bleeding in the interval between screening examinations. SIR was 4.0 (95% confidence interval, 1.39.4) and increased to 4.8 (CI, 1.6-10.5) when the single cancer detected at first screening was considered as incident. Conclusions This study adds evidence to the hypothesis that long-term tamoxifen treatment may be responsible for a relevant increase in the risk of developing endometrial cancer. Surveillance based on endometrial ultrasonography was poorly sensitive, but the favorable stage at diagnosis of screen-detected or interval endometrial cancers does not support a more aggressive screening approach.
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Bryant, Christopher, Jay Shah, Sanjeev Kumar, Adnan Munkarah, Robert Morris, and Gunter Deppe. "Sacral metastases in an endometrial cancer patient after treatment with sequential chemo-radiotherapy: A case report." Archive of Oncology 18, no. 1-2 (2010): 38–39. http://dx.doi.org/10.2298/aoo1002038b.

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The incidence of bone metastases in endometrial cancer is reported to occur in less than 15% of patients with metastatic disease. The medical literature is limited to only case reports, although none describing a sacral recurrence after adjuvant chemo-radiation therapy. We present the case of a 64-year-old woman who underwent surgery for endometrial adenocarcinoma followed by 'sandwich' chemoradiation therapy at our institution, July 2006 (FIGO stage IB grade 3). In spite of adjuvant therapy, which was delivered in August 2008 the patient, developed an isolated sacral recurrence. The optimal therapeutic modality for endometrial cancer patients with high-risk disease remains controversial. The increasing use of combined modality therapy for early stage, high-risk patients may produce different recurrence patterns than described in historical controls.
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Hara, Fumikata, Sachiko Kiyoto, Daisuke Takabatake, Seiki Takashima, Kenjiro Aogi, Shozo Ohsumi, Norihiro Teramoto, Rieko Nishimura, and Shigemitsu Takashima. "Endometrial Metastasis from Breast Cancer during Adjuvant Endocrine Therapy." Case Reports in Oncology 3, no. 2 (2010): 137–41. http://dx.doi.org/10.1159/000313921.

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Vanderstichele, Adriaan, Patrick Neven, and Ignace Vergote. "Combined modality adjuvant therapy for high-risk endometrial cancer." Lancet Oncology 17, no. 8 (August 2016): 1029–30. http://dx.doi.org/10.1016/s1470-2045(16)30152-8.

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Gadducci, Angiolo, and Carlo Greco. "The evolving role of adjuvant therapy in endometrial cancer." Critical Reviews in Oncology/Hematology 78, no. 2 (May 2011): 79–91. http://dx.doi.org/10.1016/j.critrevonc.2010.03.009.

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Jewell, E., A. A. Secord, T. Brotherton, and A. Berchuck. "Use of trastuzumab in the treatment of metastatic endometrial cancer." International Journal of Gynecologic Cancer 16, no. 3 (2006): 1370–73. http://dx.doi.org/10.1136/ijgc-00009577-200605000-00064.

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Systemic therapy of metastatic endometrial cancer is relatively ineffective. Response rates to chemotherapy and hormonal therapy in published studies range from 11% to 57%, but most responses are partial and of limited duration. In this case, we present a 76-year-old woman with stage IIIA endometrial adenocarcinoma who was initially treated with surgery and pelvic radiation. She developed multiple pulmonary metastases. She was treated with weekly paclitaxel chemotherapy. Immunostaining revealed that the primary endometrial cancer overexpressed HER-2/neu. Trastuzumab was added to the regimen, and a dramatic partial response was achieved. After a second pulmonary relapse following discontinuation of prior therapy, she was again successfully treated with trastuzumab in combination with paclitaxel and then docetaxel. Therefore, trastuzumab may be a useful adjuvant to taxane-based chemotherapy in some patients with metastatic endometrial cancers that overexpress HER-2/neu.
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Zhu, Simeng, Remonda Khalil, Osama Altairy, Charlotte Burmeister, Irina Dimitrova, and Mohamed Elshaikh. "Increased risk of recurrence in early-stage endometrial carcinoma after delays in adjuvant radiation treatment." International Journal of Gynecologic Cancer 31, no. 1 (October 21, 2020): 73–77. http://dx.doi.org/10.1136/ijgc-2020-001937.

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ObjectiveThe benefits of adjuvant radiation treatment after hysterectomy have been confirmed in select patients with early-stage endometrial carcinoma. The goal of this study was to evaluate the prognostic impact of the time interval between hysterectomy and starting adjuvant radiation treatment in patients with early-stage endometrial carcinoma.MethodsOur database was searched for women with early-stage endometrioid endometrial cancer who received adjuvant radiation therapy after hysterectomy. The patients were classified into two groups based on the time interval to adjuvant radiation therapy (≤8 weeks or >8 weeks) after hysterectomy. Recurrence-free survival, disease-specific survival, and overall survival were compared between the two groups.ResultsFour hundred and sixty patients were identified. Median follow-up was 70.5 months (range 1–360). One hundred and seventy-six patients (38%) were 2009 International Federation of Gynecology and Obstetrics stage IA, 207 (45%) stage IB, and 77 (17%) stage II. Three hundred and fifty-four women (77%) received adjuvant radiation therapy within 8 weeks after hysterectomy. There was no statistically significant difference between the two groups in baseline demographics, disease and treatment characteristics, except for the modality of adjuvant radiation therapy. Patients who received adjuvant radiation therapy within 8 weeks experienced significantly less disease recurrence (9% vs 18%; p=0.01) and particularly less isolated vaginal recurrence (0% vs 6%, p=0.04). Five-year recurrence-free survival was 89% versus 80% (p=0.04), 5-year disease-specific survival was 93% for both groups, and 5-year overall survival was 86% versus 85% for patients who received adjuvant radiation therapy ≤8 and >8 weeks, respectively (p=0.88).ConclusionOur study suggests that delaying adjuvant radiation therapy beyond 8 weeks after hysterectomy is associated with significantly more cancer recurrences for women with early-stage endometrial carcinoma.
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Milam, Michael R., Bin Huang, Mana Moghadamfalahi, Lynn Parker, Daniel Metzinger, and Thomas Tucker. "Association of adjuvant therapy in early-stage low-risk endometrial cancer with increased mortality: A statewide cancer registry analysis." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 5095. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.5095.

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5095 Background: National Comprehensive Cancer Network (NCCN) guidelines state that patients with early stage low risk endometrial cancer (defined with 2009 criteria as stage IA endometrioid endometrial cancer) may be managed with observation with consideration of adjuvant therapy.The premise of this study is to review the patterns of care of those patients who received adjuvant therapy and its impact on survival. Methods: This is a retrospective cohort analysis of 1044 women from 2004-2008 in the Kentucky Cancer Registry (KCR) one of the affiliates utilized in the Surveillance, Epidemiology and End Results (SEER) Program database. Inclusion criteria for the patients in this analysis were those women with 2009 Stage IA uterine cancer of endometrioid histology, moderate and well differentiated tumor grade, who received definitive primary surgery. Adjuvant therapy was defined as any postoperative radiotherapy and/or chemotherapy after definitive surgical treatment. Patients with adjuvant therapy after surgery (AT) were compared to those patients who underwent surgery only (SO). Chi-square tests were used to identify associations between type of treatment and clinical/demographic factors. K-M plots and Cox regression models were used to examine survival between the two treatment groups. Results: 5.3% (55/1044) of patients with early stage low risk endometrial cancer were treated with AT compared to 94.7% (989/1044) of SO patients.No statistical differences in mean age, race, tumor size, smoking status, insurance status, lymph node dissection and gynecologic oncology care were found among the AT or SO groups. Five year survival was significantly better in the SO cohort compared to the AT cohort (92% alive at 5 years for SO vs. 66% alive at 5 years; p<0.0001). Controlling for other confounders in the multivariate Cox regression analysis, SO patients had substantially less risk for death compared to the AT groups (HR: 0.21; 95%CI 0.12-0.38; p<0.0001). Conclusions: In this statewide cancer registry analysis, adjuvant therapy after surgery in early stage low risk endometrial cancer patients is uncommon and is associated with an increased risk of mortality.
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Amir, Eitan, Mustafa Al-Mubarak, Ariadna Tibau, Arnoud J. Templeton, Alberto Ocana, and Bostjan Seruga. "Extended adjuvant tamoxifen for early breast cancer: A meta-analysis." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 539. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.539.

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539 Background: Hormone receptor positive breast cancer is characterized by the potential for disease recurrence many years after initial diagnosis. Endocrine therapy has been shown to reduce the risk of such recurrence, but the optimal duration of endocrine therapy remains unclear. Methods: We conducted a systematic review and meta-analysis to quantify the relative and absolute benefits and harms of extended adjuvant tamoxifen (>5 years of therapy) compared with adjuvant tamoxifen (≤5 years of therapy). Odds ratios (ORs), 95% confidence intervals (CIs), absolute risks, and the number needed to treat (NNT) were computed for pre-specified events including disease recurrence, distant recurrence, all-cause death, endometrial carcinoma, cardiovascular death and treatment discontinuation. Subgroup analyses by timing of recurrence and baseline lymph node and menopause status were carried out. Results: Six trials comprising 25,326 patients were included. Extended adjuvant tamoxifen was associated with a non-significant reduction in the risk of recurrence (OR 0.89, 95% CI 0.77-1.04, p=0.14, NNT 74). Similar results were seen for distant recurrence (OR 0.88, 95% CI 0.75-1.04, p=0.14, NNT 70). There was no association between extended adjuvant tamoxifen and all-cause death (OR 1.06, 95% CI 0.86-1.31, p=0.58). There was no reduction in risk during extended adjuvant therapy (i.e. between years 5 and 9), but a potential reduction in the risk of recurrence after completion of extended adjuvant tamoxifen (i.e. beyond 10 years after diagnosis). Subgroup analysis suggested benefit in lymph node positive patients. Endometrial carcinoma was substantially more frequent with extended adjuvant tamoxifen (OR 1.81, 95% CI 1.45-2.25, p<0.001, NNT 102), but among those with endometrial carcinoma, the odds of death were lower among the extended tamoxifen group (OR 0.50, 95% CI 0.28-0.90, p=0.02). Conclusions: Extended adjuvant tamoxifen is not associated with a significant reduction in recurrence or death in unselected patients. Patients with lymph node positive breast cancer may derive more benefit. Reduction in the risk of recurrence only appears after completion of extended adjuvant therapy.
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Lee, Jung-Yun, Jae Weon Kim, Taek Sang Lee, Rongyu Zang, Xiaojun Chen, Jiaxin Yang, Kung-Liahng Wang, and Toru Sugiyama. "Difference in Practice Patterns in the Management of Endometrial Cancer: A Survey of the Members of 4 East Asian Gynecologic Oncology Groups." International Journal of Gynecologic Cancer 27, no. 9 (November 2017): 1888–94. http://dx.doi.org/10.1097/igc.0000000000001078.

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ObjectiveThe aim of this article was to identify current practice patterns of care in the surgical and adjuvant management of endometrial cancer in East Asia (Korea, Japan, China, and Taiwan)MethodsA validated 20-item questionnaire on surgical and adjuvant procedures for endometrial cancer was sent to active members of the Gynecologic Oncology Group from 4 East Asian countries. Data were collected using an Internet survey database.ResultsA total of 376 members from Korea (n = 108), Japan (n = 140), China (n = 51), and Taiwan (n = 77) responded to the survey. With respect to early-stage endometrial cancer, laparotomy (57.7%) was the most preferred mode of surgery in Japan, whereas laparoscopy was the most common in the remaining 3 countries. For patients with presumed stage IA/G1 disease, approximately 65% of respondents favored systematic lymphadenectomy. For patients with presumed stage IB disease, most respondents stated that systematic lymphadenectomy should be performed (92.6% for stage IBG1, 95.8% for stage IBG3). Meanwhile, the extents of lymphadenectomy differed among countries (P < 0.001). Considerable agreement was noted between countries regarding indications for adjuvant therapy for stage IIIA or IIIC1 disease, whereas the preferred options for adjuvant therapy varied according to country (P < 0.001). Specifically, chemotherapy was the most common selection option in Japan, whereas concurrent chemoradiotherapy was preferred in the other countries.ConclusionsConsiderable agreement was identified with respect to the necessity for lymphadenectomy for surgical staging and the indications for adjuvant therapy. However, extents of surgery and preferred adjuvant treatment options for endometrial cancer varied widely between countries.
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McGunigal, Mary, Ariel Pollock, John T. Doucette, Jerry Liu, Manjeet Chadha, Tamara Kalir, and Vishal Gupta. "Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate–Risk Stage I Endometrial Cancer." International Journal of Gynecologic Cancer 28, no. 5 (June 2018): 882–89. http://dx.doi.org/10.1097/igc.0000000000001245.

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ObjectivesRandomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate–risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT.MethodsThe National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/− adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days’ follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1–2.ResultsSeventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012; the difference between 1998–2004 and 2005–2010 was not statistically significant.ConclusionsFewer than half of patients with high-intermediate–risk endometrial cancer by Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria received adjuvant RT despite evidence demonstrating improved local control. Both patient- and tumor-related factors are associated with delivery of adjuvant RT and the modality selected.
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Zagouri, Flora, George Bozas, Eftichia Kafantari, Marinos Tsiatas, Nikitas Nikitas, Meletios-A. Dimopoulos, and Christos A. Papadimitriou. "Endometrial Cancer: What Is New in Adjuvant and Molecularly Targeted Therapy?" Obstetrics and Gynecology International 2010 (2010): 1–11. http://dx.doi.org/10.1155/2010/749579.

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Endometrial cancer is the most common gynaecological cancer in western countries. Radiotherapy remains the mainstay of postoperative management, but accumulating data show that adjuvant chemotherapy may display promising results after staging surgery. The prognosis of patients with metastatic disease remains disappointing with only one-year survival. Progestins represent an effective option, especially for those patients with low-grade estrogen and/or progesterone receptor positive disease. Chemotherapy using the combination of paclitaxel, doxorubicin, and cisplatin is beneficial for patients with advanced or metastatic disease after staging surgery and potentially for patients with early-stage disease and high-risk factors. Toxicity is a point in question; however, the combination of paclitaxel with carboplatin may diminish these concerns. In women with multiple medical comorbidities, single-agent chemotherapy may be better tolerated with acceptable results. Our increased knowledge of the molecular aspects of endometrial cancer biology has paved the way for clinical research to develop novel targeted antineoplastic agents (everolimus, temsirolimus, gefitinib, erlotinib, cetuximab, trastuzumab, bevacizumab, sorafenib) as more effective and less toxic options. Continued investigation into the molecular pathways of endometrial cancer development and progression will increase our knowledge of this disease leading to the discovery of novel, superior agents.
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AlHilli, Mariam, Paul Elson, Lisa Rybicki, Sudha Amarnath, Bin Yang, Chad M. Michener, and Peter G. Rose. "Undifferentiated endometrial carcinoma: a National Cancer Database analysis of prognostic factors and treatment outcomes." International Journal of Gynecologic Cancer 29, no. 7 (August 17, 2019): 1126–33. http://dx.doi.org/10.1136/ijgc-2019-000465.

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BackgroundUndifferentiated endometrioid endometrial carcinoma of the uterus is a rare, highly aggressive, and under-recognized subtype of endometrial cancer.ObjectiveThis study evaluates survival, prognostic factors for survival, and treatment outcomes associated with undifferentiated endometrial cancer.MethodsThe National Cancer Database was queried to identify patients with undifferentiated endometrial cancer who underwent definitive primary surgical treatment. Patients with all other histologic subtypes or incomplete treatment data were excluded. Univariable and multivariable Cox proportional hazards analyses were used to determine independent prognostic factors for survival. Points for each prognostic factor were assigned from regression coefficients in the final multivariable model and summed for a total score. Recursive partitioning analysis was used to determine cut-offs in the score to identify unique prognostic groups.ResultsAmong 349 404 women diagnosed with endometrial cancer from 2004 to 2013, 3994 (1.1%) met the criteria for diagnosis of undifferentiated endometrial cancer and 3486 had survival data. Median age at diagnosis was 65 years (interquartile range (IQR) 57–74) and 58% of patients had early stage disease. Median interval from diagnosis to surgery was 3.7 weeks (IQR 2.0–5.7). Five year overall survival was 57% (standard error (SE) 1%). Stage was the strongest predictor of survival, with a 15–20% decrement in 5 year survival for each advance in stage. Stage, age, race, and presence of comorbidities were independent predictors of survival and were used to categorize patients into five prognostic groups. Adjuvant therapy was associated with improved survival across most disease stages and prognostic groups. Multimodal adjuvant therapy was superior to unimodal treatment particularly in advanced stage unfavorable and very unfavorable groups.ConclusionIn women with undifferentiated endometrial cancer, survival is primarily driven by stage. Despite the poor overall prognosis of undifferentiated endometrial cancer, multimodal adjuvant therapy is a key component of treatment.
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Emons, Günter, Eric Steiner, Dirk Vordermark, Christoph Uleer, Nina Bock, Kerstin Paradies, Olaf Ortmann, et al. "Interdisciplinary Diagnosis, Therapy and Follow-up of Patients with Endometrial Cancer. Guideline (S3-Level, AWMF Registry Number 032/034-OL, April 2018) – Part 2 with Recommendations on the Therapy and Follow-up of Endometrial Cancer, Palliative Care, Psycho-oncological/Psychosocial Care/Rehabilitation/Patient Information and Healthcare Facilities." Geburtshilfe und Frauenheilkunde 78, no. 11 (November 2018): 1089–109. http://dx.doi.org/10.1055/a-0715-2964.

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Abstract Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose Using evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal extent of surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy if required. An evidence-based optimal use of different therapeutic modalities should improve the survival rates and quality of life of these patients. This S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources included reviews of evidence, which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one part of the guideline. Identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then subsequently modified during structured consensus conferences and/or additionally amended online using the DELPHI method, with consent between members achieved online. The guideline report is freely available online. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of endometrial cancer including precancers and early endometrial cancer as well as recommendations on palliative medicine, psycho-oncology, rehabilitation, patient information and healthcare facilities to treat endometrial cancer. The management of precancers of early endometrial precancerous conditions including fertility-preserving strategies is presented. The concept used for surgical primary therapy of endometrial cancer is described. Radiotherapy and adjuvant medical therapy to treat endometrial cancer and uterine carcinosarcomas are described. Recommendations are given for the follow-up care of endometrial cancer, recurrence and metastasis. Palliative medicine, psycho-oncology including psychosocial care, and patient information and rehabilitation are presented. Finally, the care algorithm and quality assurance steps for the diagnosis, therapy and follow-up of patients with endometrial cancer are outlined.
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Lester-Coll, Nataniel H., Melissa R. Young, Henry S. Park, Elena S. Ratner, Babak Litkouhi, and Shari Damast. "Adjuvant Therapy Use and Survival in Stage II Endometrial Cancer." International Journal of Gynecologic Cancer 27, no. 9 (November 2017): 1904–11. http://dx.doi.org/10.1097/igc.0000000000001095.

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ObjectiveRadiotherapy (RT) is an established adjuvant treatment for stage II endometrioid endometrial carcinoma (EEC). The role of chemotherapy (CT) in stage II EEC is less proven. We used the National Cancer Data Base to identify factors associated with adjuvant CT in stage II EEC and to explore whether receipt of CT was associated with improved overall survival (OS).Methods/MaterialsWomen diagnosed in 2010 to 2013 with International Federation of Obstetrics and Gynecology stage II EEC (grades 1–3) after hysterectomy and bilateral salpingo-oophorectomy were identified in the National Cancer Data Base. Multivariable logistic regression was used to identify covariates associated with receipt of CT. Overall survival among patients receiving RT, CT, or chemoradiotherapy (CRT) after surgery was compared using Kaplan-Meier estimates, the log-rank test, Cox proportional hazards regression, and propensity score matching.ResultsWe identified 6102 stage II EEC patients. There were 358 patients (6%) who received adjuvant CT alone and 525 (9%) who received CRT; the remainder received RT alone (n = 1906; 31%) or no adjuvant treatment (n = 3313; 54%). The presence of lymphovascular invasion (odds ratio, 3.58;P< 0.001) and grade 3 disease (odds ratio, 3.40;P< 0.001) was strongly associated with receipt of CT or CRT. The OS at 3 years for the entire cohort was 89%. On multivariable analysis, CT versus RT was associated with worse OS (hazard ratio [HR], 2.12 [95% confidence interval, 1.46–3.06];P< 0.001), whereas CRT versus RT was not associated with improved OS (HR, 1.07 [95% confidence interval, 0.71–1.62];P= 0.781). After propensity score matching, there remained no difference in OS between RT and CRT (HR, 1.14;P= 0.614).ConclusionsPatients with stage II EEC have an excellent prognosis, and most undergo observation or receive adjuvant RT in the United States. Receipt of CT (alone or with RT) was not associated with an OS advantage compared with RT alone in this observational cohort. Randomized trials will help clarify the role of CT in stage II patients.
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Zaidi, Syeda Sadia, Vipul T. Lakhani, Oluwole Fadare, and Dineo Khabele. "Adrenal Gland Metastasis Is an Unusual Manifestation of Endometrial Cancer." Case Reports in Surgery 2013 (2013): 1–3. http://dx.doi.org/10.1155/2013/428456.

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This case report describes a woman treated for stage 1 B grade 3 endometrial adenocarcinoma with surgery and adjuvant radiation therapy who presented 6 months later with pain and symptoms of adrenal insufficiency. A large right adrenal mass revealed adenocarcinoma consistent with the endometrial primary.
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Montes de Oca, Mary Katherine, Benjamin B. Albright, Angeles Alvarez Secord, Laura J. Havrilesky, and Haley A. Moss. "Adjuvant treatment and outcomes for patients with stage IIIA grade 1 endometrioid endometrial cancer." International Journal of Gynecologic Cancer 31, no. 12 (November 1, 2021): 1549–56. http://dx.doi.org/10.1136/ijgc-2021-002884.

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ObjectiveThe role and type of adjuvant therapy for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIA grade 1 endometrioid endometrial adenocarcinoma are controversial. This retrospective cohort study aimed to determine associations between adjuvant therapy use and survival among patients with stage IIIA grade 1 endometrial cancer.MethodsPatients who underwent primary surgery for stage IIIA (FIGO 2009 staging) grade 1 endometrial cancer between January 2004 and December 2016 were identified in the National Cancer Database. Demographics and receipt of adjuvant therapy were compared. Overall survival was analyzed using Kaplan–Meier curves, log-rank test, and multivariable Cox proportional hazard models.ResultsOf 1120 patients, 248 (22.1%) received no adjuvant treatment, 286 (25.5%) received chemotherapy alone, 201 (18.0%) radiation alone, and 385 (34.4%) chemotherapy and radiation. Five-year overall survival rate was 83.0% (95% CI 80.1% to 85.6%). Older age, increasing comorbidity count, and lymphovascular space invasion status were significant negative predictors of survival. Over time, there was an increasing rate of chemotherapy (45.4% in 2004–2009 vs 69.2% in 2010–2016; p<0.001). In the multivariable analysis, chemotherapy was associated with significantly improved overall survival compared with no adjuvant therapy (HR 0.49 (95% CI 0.31 to 0.79); p=0.003). There was no survival association when comparing radiation alone with no treatment, and none when adding radiation to chemotherapy compared with chemotherapy alone. Those with lymphovascular space invasion (n=124/507) had improved overall survival with chemotherapy and radiation (5-year overall survival 91.2% vs 76.7% for chemotherapy alone and 27.3% for radiation alone, log-rank p<0.001), but there was no survival difference after adjusting for age and comorbidity (HR 0.25 (95% CI 0.05 to 1.41); p=0.12).ConclusionsThe use of adjuvant chemotherapy for the treatment of stage IIIA grade 1 endometrial cancer increased over time and was associated with improved overall survival compared with radiation alone or chemoradiation. Patients with lymphovascular space invasion may benefit from combination therapy.
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van den Heerik, Anne Sophie V. M., Nanda Horeweg, Carien L. Creutzberg, and Remi A. Nout. "Vaginal brachytherapy management of stage I and II endometrial cancer." International Journal of Gynecologic Cancer 32, no. 3 (March 2022): 304–10. http://dx.doi.org/10.1136/ijgc-2021-002493.

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Adjuvant radiotherapy is an important component of post-operative therapy for patients with early-stage endometrial cancer. In the past decades, many trials have been conducted to determine the optimal adjuvant treatment strategy, pelvic external beam radiotherapy or vaginal brachytherapy. As a result, vaginal brachytherapy became the treatment of choice for patients with early-stage endometrial cancer at high-intermediate risk, based on clinicopathological risk factors. Vaginal brachytherapy maximizes local control and has only mild side effects with limited impact on quality of life, in comparison with pelvic external beam radiotherapy. The most frequently used treatment schedule is the one which was used in the PORTEC-2 trial (21 Gy in three fractions specified at 5 mm depth) and, whenever available, image-guided brachytherapy should be used. However, the most convenient and effective treatment schedule remains to be established. More recently, the discovery and integration of four molecular classes in the risk assessment of endometrial cancer patients has created new opportunities to prevent over- and undertreatment. The 2021 endometrial cancer guideline of the European Society of Gynaecological Oncology (ESGO), European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) now proposes an integrated risk stratification, in which both clinicopathologic and molecular factors are combined, to direct adjuvant therapy. This rationale is now investigated in multiple prospective trials. This review provides an overview of the rationale and currently recommended and new strategies for vaginal brachytherapy in patients with stage I and II endometrial cancer.
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Otsuka, Isao. "Therapeutic Benefit of Systematic Lymphadenectomy in Node-Negative Uterine-Confined Endometrioid Endometrial Carcinoma: Omission of Adjuvant Therapy." Cancers 14, no. 18 (September 17, 2022): 4516. http://dx.doi.org/10.3390/cancers14184516.

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Endometrial cancer is the most common gynecological tract malignancy in developed countries, and its incidence has been increasing globally with rising obesity rates and longer life expectancy. In endometrial cancer, extrauterine disease, in particular lymph node metastasis, is an important prognostic factor. Nevertheless, pelvic lymphadenectomy is not considered to have a therapeutic benefit, as it did not improve survival in randomized studies. However, lymphadenectomy may have a therapeutic benefit if adjuvant therapy can be omitted without decreasing oncological outcomes, as the long-term quality of life is maintained by avoiding morbidities associated with adjuvant therapy. In intermediate- and high-risk endometrioid endometrial carcinomas, adjuvant therapy may be safely omitted without decreasing long-term survival by open surgery including systematic pelvic and para-aortic lymphadenectomy when patients are node-negative. Systematic lymphadenectomy may remove undetectable low-volume lymph node metastasis in both pelvic and para-aortic regions, and open surgery may reduce vaginal recurrence even without vaginal brachytherapy. However, lymphadenectomy may not improve survival in elderly patients and patients with p53-mutant tumors. In this review, I discuss the characteristics of lymph node metastasis, the methods of lymph node assessment, and the therapeutic benefits of systematic lymphadenectomy in patients with intermediate- and high-risk endometrioid endometrial carcinoma.
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Li, Richard, Ashwin Shinde, Ernest Han, Stephen Lee, Sushil Beriwal, Matthew Harkenrider, Mitchell Kamrava, Yi-Jen Chen, and Scott Glaser. "A proposal for a new classification of “unfavorable risk criteria” in patients with stage I endometrial cancer." International Journal of Gynecologic Cancer 29, no. 7 (September 2019): 1086–93. http://dx.doi.org/10.1136/ijgc-2019-000264.

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BackgroundRandomized trials describe differing sets of high–intermediate risk criteria.ObjectiveTo use the National Cancer Database to compare the impact of radiation therapy in patients with stage I endometrial cancer meeting different criteria, and define a classification of “unfavorable risk.”MethodsPatients with stage I endometrial cancer between January 2010 and December 2014 were identified in the National Cancer Database and stratified into two cohorts: (1) patients meeting Gynecologic Oncology Group (GOG)-99 criteria only for high–intermediate risk, but not Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 criteria and (2) those meeting PORTEC-1 criteria only. High-risk stage I patients with both FIGO stage IB (under FIGO 2009 staging) and grade 3 disease were excluded. In each cohort, propensity score-matched survival analyses were performed. Based on these analyses, we propose a new classification of unfavorable risk. We then analyzed the association of adjuvant radiation with survival, stratified by this classification.ResultsWe identified 117,272 patients with stage I endometrial cancer. Of these, 11,207 patients met GOG-99 criteria only and 5,920 patients met PORTEC-1 criteria only. After propensity score matching, adjuvant radiation therapy improved survival (HR=0.73; 95% CI 0.60 to 0.89; p=0.002) in the GOG-99 only cohort. However, there was no benefit of adjuvant radiation (HR=0.89; 95% CI 0.69 to 1.14; p=0.355) in the PORTEC-1 only cohort. We, therefore, defined unfavorable risk stage I endometrial cancer as two or more of the following risk factors: lymphovascular invasion, age ≥70, grade 2–3 disease, and FIGO stage IB. Adjuvant radiation improved survival in stage I patients with adverse risk factors (HR=0.74; 95% CI 0.68 to 0.80; p<0.001), but not in other stage I patients (HR=1.02; 95% CI 0.91 to 1.15; p=0.710; p interaction <0.001).ConclusionOur study showed that adjuvant radiation was associated with an overall survival benefit in patients meeting GOG-99 criteria only; however, no survival benefit was seen in patients meeting PORTEC-1 criteria only. We propose a definition of unfavorable risk stage I endometrial cancer: ≥2 risk factors from among lymphovascular invasion, age ≥70, grade 2–3 disease, and FIGO stage IB disease.
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44

Charo, Lindsey M., and Steven C. Plaxe. "Recent advances in endometrial cancer: a review of key clinical trials from 2015 to 2019." F1000Research 8 (June 12, 2019): 849. http://dx.doi.org/10.12688/f1000research.17408.1.

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In the past few years, we have seen several important advances in understanding of and therapy for endometrial cancer. This review highlights key recent abstracts and publications in endometrial cancer from 2015 to 2019. We focus on clinical trials in surgical staging and the utility of sentinel lymph node mapping, adjuvant treatment for high-risk disease and HER2/neu-positive serous tumors, combination therapy for recurrent disease, molecular biology, and immunotherapy.
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45

Buras, Andrea L., Adrianne Mallen, Robert Wenham, and Michael Montejo. "Stage IIIC endometrial cancer review: Current controversies in adjuvant therapy." Gynecologic Oncology Reports 36 (May 2021): 100754. http://dx.doi.org/10.1016/j.gore.2021.100754.

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46

Gerszten, Faul, and Huang. "Pathologic stage III endometrial cancer treated with adjuvant radiation therapy." International Journal of Gynecological Cancer 9, no. 3 (May 1999): 243–46. http://dx.doi.org/10.1046/j.1525-1438.1999.99028.x.

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47

Cowan, Matthew, Jonathan B. Strauss, Emma L. Barber, and Daniela Matei. "Updates on adjuvant chemotherapy and radiation therapy for endometrial cancer." Current Opinion in Obstetrics and Gynecology 31, no. 1 (February 2019): 31–37. http://dx.doi.org/10.1097/gco.0000000000000506.

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48

Klopp, A. H., A. Jhingran, A. Juloori, V. Perinjelil, R. Broaddus, K. Lu, and P. Eifel. "Management of Node-Positive Endometrial Cancer With Multimodality Adjuvant Therapy." International Journal of Radiation Oncology*Biology*Physics 84, no. 3 (November 2012): S455. http://dx.doi.org/10.1016/j.ijrobp.2012.07.1204.

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49

Ackerman, Ida. "Adjuvant Pelvic Radiation Therapy in Endometrial Cancer: The Pro Argument." International Journal of Gynecologic Cancer 20, Suppl 2 (September 2010): S67—S69. http://dx.doi.org/10.1111/igc.0b013e3181f66743.

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Adjuvant external beam pelvic radiation therapy for stage I endometrial cancer has become increasingly confusing and controversial. Despite repeated studies showing a disease-free survival benefit to the therapy, its role is being questioned because overall survival has not been demonstrated.By using evidence from the literature, including the most recent randomized data, an argument is made for the use of external beam pelvic radiotherapy for a 63-year-old woman who has undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a grade 2 endometrioid adenocarcinoma of the uterus with 9 of 12 mm of invasion and the presence of lymphovascular space involvement. Her risk of relapse is approximately 25%, and adjuvant external beam radiation can improve her disease-free survival and even possibly improve her chances of cure.
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50

Mehra, Dolly, and Anjum Saiyyed. "Endometrial stromal sarcoma: a rare form of undifferentiated endometrial cancer." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 10, no. 11 (October 27, 2021): 4315. http://dx.doi.org/10.18203/2320-1770.ijrcog20214065.

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Uterine sarcomas are a rare for of uterine cancers. They account for 0.2% of uterine cancers. The median age group is 40 to 60 years. They run an indolent course. About 60% women recur after a long period. Metastasis may occur even after 20 years. They can be classified into low grade, high grade and undifferentiated types. Low grade ESS has good prognosis. Surgery with adjuvant hormonal therapy is the mainstay of treatment. Adjuvant radiotherapy and chemotherapy have no role in management. The role of lymphadenectomy is not clear. The first line treatment for recurrence is a repeat surgery. Patients require a long term follow up to detect recurrence. Here we present a case of perimenopausal women presenting as a case of AUB. MRI initially diagnosed it as a case of fibroid. Patient underwent TAH with BSO. Subsequent hispathology and immunohistochemistry revealed it to be Low grade ESS. Although rare, endometrial stromal sarcoma should be considered as a differential diagnosis in perimenopausal and postmenopausal women presenting as AUB.
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