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Prognostic factors in endometrial cancer patients with bone metastasis

Zehra Ozturk Basarir1, Mustafa Onur Karaca2, Kamil Balaban2, Kerem Basarir2, Huseyin Yusuf Yildiz2

1Department of Gynecology and Obstetrics, Ankara City Hospital, Ankara, Türkiye
2Department of Orthopedics and Traumatology, Ankara University Faculty of Medicine, Ankara, Türkiye

Keywords: Bone metastasis, endometrial cancer, prognosis, surgical treatment, survival.

Abstract

Objectives: This study aims to examine the pattern and prognosis of osseous involvement and the role of orthopedic surgery in patients with endometrial cancer (EC) and to evaluate the quality of life, local tumor control, and survival of patients.

Patients and methods: Between January 2011 and December 2018, a total of 14 patients (median age: 60.5 years; range, 55 to 73 years) who were surgically treated for osseous metastasis of EC and followed for minimum 12 months were retrospectively analyzed. All patients were evaluated for their primary malignancy, characteristics of bone metastasis, and type of treatment related to musculoskeletal involvement. For evaluating the functional outcomes, the Visual Analog Scale (VAS) for pain and Eastern Cooperative Oncology Group (ECOG) performance status scale were used in the pre- and postoperative period.

Results: The median follow-up was 34.5 (range, 9 to 89) months. All patients had advanced-stage disease (FIGO Stage III-IV). Four patients had solitary and 10 patients had multiple bone metastases. The mean VAS score and ECOG performance status grades improved (p<0.001 and p<0.05, respectively). The median survival after detection of bone metastasis was 61 (range, 41 to 82) months.

Conclusion: Endometrial cancer patients with musculoskeletal pain should be investigated for the possibility of bone metastasis to tailor a prompt treatment and to achieve a better prognosis. Appropriate surgical treatment of bone metastasis may improve both pain and performance status in carefully selected patients.

Introduction

Endometrial cancer (EC) is the most common gynecologic cancer and has an increased incidence worldwide.[1-3] Although early-stage EC is known to have a very good prognosis with adequate treatment, onethird of these patients experience distant metastasis.[4] Endometrial cancer-related deaths are mostly due to distant metastases reducing overall survival.[5]

Bone metastases (BMs) in EC have been rarely reported and seen in only 0.8% of the patients.[6-9] The incidence has increased due to prolonged disease control and the use of improved radiological studies with ease. Most patients are diagnosed with BM in the recurrent setting and have extraosseous dissemination with multiple sites of BM.[10] This advanced stage usually results in poor survival in women with the metastatic disease, if theinitial diagnosis or relapse was considered incurable with traditional treatment modalities.[11]

While managing EC patients, the presence of an oligometastatic state is not commonly recognized. It is usually defined as a state of controlled or resected primary site with a few metastases (1-3 or 1-5) that has proven.[12] Solitary or oligometastasis of the bone should not be evaluated as the same with multiple metastases. There is a number of patients who develop isolated metastases in specific anatomic sites and have long-term survival after appropriately targeted treatment. A radical treatment rather than palliation of pain and preventing pathological fractures is needed in these patients. In particular, when the primary lesion is under control, this approach may lead to a long-term survival that has been shown in small series.[13]

The pattern of BM of EC is not largely described in the literature in this specific background. It is essential to understand metastasis patterns to gain a better prognosis with the proper patient management. When a distant metastasis to the bone is detected for this rare clinical entity, we believe that all patients do not have the same prognosis for different metastasis locations, the number of metastasis, or types of orthopedic surgery. In the present study, we aimed to investigate the pattern and prognosis of osseous involvement in patients with EC to better understand the role of orthopedic intervention in this patient population.

Patients and Methods

This single-center, retrospective study was conducted at Ankara University Faculty of Medicine, Department of Orthopedics and Traumatology between January 2011 and December 2018. Patients who underwent orthopedic surgeries for metastatic gynecological cancers in our center were reviewed. A total of 14 patients (median age: 60.5 years; range, 55 to 73 years) with BM due to EC and with a minimum of 12 months of follow-up were included in this study. The confirmation of EC metastasis was performed with imaging studies followed by bone biopsy and confirmed with a review of the pathology database for all patients after orthopedic surgery. We documented the International Federation of Gynecology and Obstetrics (FIGO) stage and grade which were recorded after the diagnosis of EC in patients. The FIGO stage is a surgical staging system for EC that is commonly used to state the disease stage without uncertainty among clinicians and to predict patients' outcomes and prognosis.[14] Tumor grade, also called the FIGO grade, is defined by the degree of glandular differentiation in a 3-tiered grading system; i.e., Grade 1, 2, and 3.[15]

After the medical records were systematically reviewed, patients with missing clinical data (n=3) and follow-up for less than one year were excluded from the study. Data including patient characteristics and primary tumor features such as the FIGO stage and grade, type of received treatment, and visceral organ metastasis were recorded. There were three types of treatment modalities: chemotherapy, radiation therapy, and surgery defined as “Yes” or “No”. Clinical presentation and characteristics of musculoskeletal involvement, chosen orthopedic surgery modality, and follow-up data were collected. The patients' functional outcomes were evaluated with the Visual Analog Scale (VAS) for pain and the Eastern Cooperative Oncology Group (ECOG) performance status scale for level of functioning.[16,17] All measurements were noted for pre- and postoperative three months. The ECOG performance status scale, which is a tool for physicians to follow changes during or after treatment, represents the patient's capacity for daily living activities and self-care. This scale has scores ranging from 0 to 5, where 0 represents fully active, 4 indicates the completely disabled meaning limited to a chair or bed, and 5 indicates death. We only emphasized the results of the nearest preoperative and three-month-after assessments to avoid the effect of cancer recurrence on patient outcomes.

Statistical analysis

Statistical analysis was performed using the IBM SPSS version 22.0 software (IBM Corp., Armonk, NY, USA). Descriptive data were expressed in mean ± standard deviation (SD), median (min-max) or number and frequency, where applicable. The paired t-test was used for comparison of parametric variables. The Kaplan-Meier method was used to estimate survival curves. A p value of <0.05 was considered statistically significant.

Results

The histological diagnosis of EC for all patients was an endometrioid carcinoma. Patients' demographics and characteristics of primary tumors, BM, and associated clinical data are summarized in Table I.

Table 1. Demographic, clinical, and operative data of patients

The median follow-up was 34.5 (range, 9 to 89) months. At the initial diagnosis, all patients had advanced-stage disease (FIGO Stage III-IV). Thirteen patients (92.9%) received gynecological treatment initially and only one patient (7.1%) with an advanced clinical stage (FIGO Stage IVA) did not receive surgical treatment as the first-line treatment for EC. In the majority of the patients (72%), FIGO grades were poorly differentiated (Grade 3), and only 28% of the patients had Grade 1 disease. No distant metastasis, except for bone, was identified in four (28.6%) patients.

Bone metastasis was detected at a median of 34.4 (range, 0 to 96) months after the initial diagnosis of EC. Two (14%) patients had bone pain located at the site of BM which was present at the time of the initial diagnosis.

Ten (71%) patients developed BM as their first recurrence, while two (14%) patients developed BM as a later recurrence. In these 12 patients, the overall median time from the initial diagnosis of EC to BM was 38.5 (range, 3 to 96) months. All patients had pain complaints located in the BM sites that was later confirmed.

All patients were treated for BM. Intractable/ refractory pain in nine patients (64%) and pathological fracture in five (36%) patients were the indications for orthopedic surgery. Most patients were treated with a combination of therapies, while there was no standard protocol. Wide resection of the bone lesion with or without reconstruction was done in 10 (71.4%) patients and intralesional resection in four (28.6%) patients could be achieved. Ten (71.4%) patients received radiation therapy after orthopedic surgery and one (7.1%) patient received chemotherapy after orthopedic surgery. Hormonal therapy was given to one (7.1%) patient combined with the other treatments.

Four (28.6%) patients had solitary BM and no other distant metastasis was detected. One of these patients (Patient No. 1) was diagnosed with EC and simultaneously detected BM on the iliac bone. The other three patients were diagnosed with EC by solitary bone lesions. Ten (71.4%) patients had other distant metastases in addition to bone including lymph nodes, lung, liver, and adrenal gland.

The median time from the diagnosis of BM to death in the group who had multiple sites of metastasis along with bone was 52 (range, 27 to 77) months. However, no statistical comparison could be performed, as the patients who had isolated BM were all alive and sample size was limited.

The overall median survival for EC patients in our study was 163 (range, 46 to 280) months (Figure 1). The median survival for patients with BM at the time of initial diagnosis and patients had BM at the time of recurrence could not be compared due to the limited number of patients. The patients who had BM at the initial diagnosis were still alive: alive with disease (n=1) and with no sign (n=1).

Figure 1. The Kaplan-Meier survival curve showing overall median disease-specific survival for the entire cohort.

Six (42.9%) patients died from primary disease, five (35.7%) patients were alive with no sign of disease recurrence, and three (21.4%) patients were alive without remission. New BMs were detected in one patient (Patient No. 12) during follow-up and no other orthopedic surgery was performed simultaneously. Although resection arthroplasty was performed for solitary osseous metastasis to acetabulum in Patient No. 7, it was evaluated as alive with disease due to a short period of follow-up (i.e., 14 months). One lesion in the liver was diagnosed as a first recurrence during follow-up in Patient No. 10 and non-surgical treatment was given.

The median survival after detection of BM was 61 (range, 41 to 82) months (Figure 2).

Figure 2. The Kaplan-Meier survival curve showing survival after bone metastases from endometrial cancer.

There was a statistically significant reduction in pain at the postoperative three-month VAS scores compared to baseline (from 8±0.9 to 2.8±0.6; p<0.001). All 14 (100%) patients reported pain relief after orthopedic surgery. The mean preoperative ECOG performance status for all patients reduced from 2.4±0.9 to 1.6±0.7 at three months postoperatively, indicating a statistically significant improvement (p<0.05). However, the ECOG performance status improved in only 10 of the 14 patients (71%).

Two (14.3%) patients developed complications such as wound dehiscence, and neither two of them needed debridement.

Discussion

The presence of BMs is accepted to be a poor prognostic factor in a wide range of solid tumors, including breast and gynecological cancers.[18] However, with a small sample size of EC with BM patients, caution should be applied, as the number of metastasis and metastasis pattern may not be transferable to all patients. Some patients have solitary lower extremity or pelvic BM with the recurrence of the primary cancer with a more favorable metastasis. On the other hand, there are some high-grade patients with multiple organ involvement together with extra-pelvic bone with aggressive features. These may consistently explain the poorer prognosis for these patients compared to those with solitary BM.

In the current study, the timing of BM was of utmost importance. Significantly longer overall survival was also reported in patients with BM at the time of recurrence compared to those patients with BM at diagnosis of EC.[19] Location of the metastasis is also another prognostic factor. Extra-pelvic metastasis and particularly solitary bone were significantly associated with longer overall survival.[19] Consistent with the literature, two patients in our series developed solitary-extra-pelvic BM in the femur and fibula, respectively 96 and 75 months after the initial diagnosis, they were both alive with no evidence of disease recurrence 74 and 84 months after resection of BM, respectively. Isolated lower extremity involvement was demonstrated in various case reports.[20-43] It may also occur as the first sign of EC without any history of vaginal bleeding or other gynecological symptoms.[6,7,23,25,27,30-35,37,38,40-54] Biopsy usually reveals an adenocarcinoma and the definitive diagnosis can be only made after diagnostic work-up for gynecologic cancers, such as abdominal ultrasound and uterine curettage.[41] Even if in this rare presentation without any gynecological symptoms of Stage IVB EC, the aforementioned authors reported good survival rates.

A review including more than 100 case reports revealed that shorter overall survival rates was observed in patients with lack of surgery (12 months), compared to surgical treatment for BM (42 months).[55] The radical treatment of solitary BM led to long-term survival in some patients. It may be concluded that the patients are in an oligometastatic state and wide surgical resection with adjuvant therapy can be curative. As shown in Figure 3, a low-grade patient with solitary BM and no other distant metastasis was treated with wide resection, and alive with no sign of disease.

Figure 3. A 60-year-old female patient (Patient No. 2) was diagnosed with a metastatic endometrial adenocarcinoma to right distal femur presenting with a pathological fracture. (a) Right distal femur x-ray showing a pathological fracture with a calcified lesion. (b) Right femoral magnetic resonance imaging (T1 coronal+contrast) showing multiple bone lesions with cortical destruction and soft tissue extension. (c) Right femoral magnetic resonance imaging (T1 axial+contrast) showing adjacent soft tissue invasion and edema. (d) Total body bone scan showing the increased uptake from right distal femur. (e) A distal femoral endoprosthesis was used to reconstruct the bone defect.

Wide surgical resection may be a reasonable option for patients with solitary BM who do not have any extra-osseous disease, and who have the primary disease under control.[8] Palliative surgery for stabilization and pain with or without radiotherapy/ chemotherapy is the treatment option for patients with multiple metastases.[18]

In the present study, we also emphasize the heterogeneity of the metastatic involvement in terms of location and the number of osseous metastases. These findings suggest that BM, particularly to the lower extremities, may be accepted as an oligometastatic state in EC. The most important issue in this context is the aggressive control of the osseous lesions in case of operability.[56] The main strengths of our study lie in the relatively large sample size and long-term follow-up.

Nonetheless, there are some limitations to this study. First, the single-center, retrospective design with a limited number of patients preclude to draw definitive conclusions. Second, even if all patients had the same primary tumor, there was a heterogeneity among surgeries and treatment modalities due to the individualized treatment modality based on decision of Multidisciplinary Tumor Council.

In conclusion, the possibility of BM should be always remembered in patients with musculoskeletal pain and should be evaluated to tailor a prompt treatment and to achieve a better prognosis. In our series, there were also multiple metastatic patients treated palliatively, as many of these patients had several comorbidities that prevented aggressive treatment procedures. These findings support the current clinical approach of aggressive treatment of single or oligometastatic disease and palliative treatment of EC patients with multiple involvements based on regarding patients’ complaints or symptoms. According to the least number of patients and heterogeneity of the treatment modalities in metastatic EC, we cannot give a straight message; however, we can speculate that orthopedic oncologic interventions can improve the patient's quality of life when combined with other modalities. Further studies are needed to establish more reliable conclusions on this subject.

Citation: Ozturk Basarir Z, Karaca MO, Balaban K, Basarir K, Yildiz HY. Prognostic factors in endometrial cancer patients with bone metastasis. Jt Dis Relat Surg 2023;34(1):207-214. doi: 10.52312/ jdrs.2023.792

Ethics Committee Approval

The study protocol was approved by the Ankara University Faculty of Medicine Human Research Ethics Committee (date: 17.06.2020, no: I5-311-20). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Author Contributions

Idea/concept: Z.O.B., M.O.K., H.Y.Y.; Design: K.B., M.O.K., K.B.; Data collection/processing: K.B.; Analysis/interpretation: Z.O.B., K.B., M.O.K., K.B.; Literature review: K.B., K.B.; Drafting/writing: K.B., M.O.K.,K.B.; Critical review: Z.O.B., H.Y.Y.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

The authors received no financial support for the research and/or authorship of this article.

References

  1. National Cancer Institute, Surveillance, Epidemiology, and End Results Program, Cancer Stat Facts: Uterine Cancer. 2020 Available at: https://seer.cancer.gov/statfacts/html/ corp.html [Accessed: May 14, 2021]
  2. Sheikh MA, Althouse AD, Freese KE, Soisson S, Edwards RP, Welburn S, et al. USA endometrial cancer projections to 2030: Should we be concerned? Future Oncol 2014;10:2561-8. doi: 10.2217/fon.14.192.
  3. Evans T, Sany O, Pearmain P, Ganesan R, Blann A, Sundar S. Differential trends in the rising incidence of endometrial cancer by type: Data from a UK population-based registry from 1994 to 2006. Br J Cancer 2011;104:1505-10. doi: 10.1038/ bjc.2011.68.
  4. Ouldamer L, Bendifallah S, Body G, Canlorbe G, Touboul C, Graesslin O, et al. Change in hazard rates of recurrence over time following diagnosis of endometrial cancer: An age stratified multicentre study from the FRANCOGYN group. Eur J Surg Oncol 2018;44:1914-20. doi: 10.1016/j. ejso.2018.07.053.
  5. Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987;60(8 Suppl):2035- 41. doi: 10.1002/1097-0142(19901015)60:8+3.0.co;2-8.
  6. Uccella S, Morris JM, Bakkum-Gamez JN, Keeney GL, Podratz KC, Mariani A. Bone metastases in endometrial cancer: Report on 19 patients and review of the medical literature. Gynecol Oncol 2013;130:474-82. doi: 10.1016/j. ygyno.2013.05.010.
  7. Kehoe SM, Zivanovic O, Ferguson SE, Barakat RR, Soslow RA. Clinicopathologic features of bone metastases and outcomes in patients with primary endometrial cancer. Gynecol Oncol 2010;117:229-33. doi: 10.1016/j. ygyno.2010.01.047.
  8. Ghosh S, Rao PB. Osseous metastases in gynaecological epithelial malignancies: A retrospective institutional study and review of literature. J Clin Diagn Res 2015;9:XC10-3. doi: 10.7860/JCDR/2015/15063.6925.
  9. Descamps P, Calais G, Moire C, Bertrand P, Castiel M, Le Floch O, et al. Predictors of distant recurrence in clinical stage I or II endometrial carcinoma treated by combination surgical and radiation therapy. Gynecol Oncol 1997;64:54-8. doi: 10.1006/gyno.1996.4511.
  10. McEachron J, Chatterton C, Hastings V, Gorelick C, Economos K, Lee YC, et al. A clinicopathologic study of endometrial cancer metastatic to bone: Identification of microsatellite instability improves treatment strategies. Gynecol Oncol Rep 2020;32:100549. doi: 10.1016/j. gore.2020.100549.
  11. Ouldamer L, Bendifallah S, Body G, Touboul C, Graesslin O, Raimond E, et al. Incidence, patterns and prognosis of first distant recurrence after surgically treated early stage endometrial cancer: Results from the multicentre FRANCOGYN study group. Eur J Surg Oncol 2019;45:672-8. doi: 10.1016/j.ejso.2019.01.011.
  12. Reyes DK, Pienta KJ. The biology and treatment of oligometastatic cancer. Oncotarget 2015;6:8491-524. doi: 10.18632/oncotarget.3455.
  13. Makris GM, Mene J, Battista MJ, Chrelias G, Sergentanis TN, Psyrri A, et al. Endometrial carcinoma with tibial bone metastasis: A case report and literature review. J Obstet Gynaecol 2018;38:1039-47. doi: 10.1080/01443615.2017.1420759.
  14. Lewin SN. Revised FIGO staging system for endometrial cancer. Clin Obstet Gynecol 2011;54:215-8. doi: 10.1097/ GRF.0b013e3182185baa.
  15. Soslow RA, Tornos C, Park KJ, Malpica A, Matias-Guiu X, Oliva E, et al. Endometrial carcinoma diagnosis: Use of FIGO grading and genomic subcategories in clinical practice: Recommendations of the International Society of Gynecological Pathologists. Int J Gynecol Pathol 2019;38 Suppl 1:S64-74. doi: 10.1097/PGP.0000000000000518.
  16. de Boer AG, van Lanschot JJ, Stalmeier PF, van Sandick JW, Hulscher JB, de Haes JC, et al. Is a single-item visual analogue scale as valid, reliable and responsive as multiitem scales in measuring quality of life? Qual Life Res 2004;13:311-20. doi: 10.1023/B:QURE.0000018499.64574.1f.
  17. Azam F, Latif MF, Farooq A, Tirmazy SH, AlShahrani S, Bashir S, et al. Performance status assessment by using ECOG (Eastern Cooperative Oncology Group) score for cancer patients by oncology healthcare professionals. Case Rep Oncol 2019;12:728-36. doi: 10.1159/000503095.
  18. Gottwald L, Dukowicz A, Piekarski J, Misiewicz B, Spych M, Misiewicz P, et al. Bone metastases from gynaecological epithelial cancers. J Obstet Gynaecol 2012;32:81-6. doi: 10.3109/01443615.2011.619672.
  19. Yoon A, Choi CH, Kim TH, Choi JK, Park JY, Lee YY, et al. Bone metastasis in primary endometrial carcinoma: Features, outcomes, and predictors. Int J Gynecol Cancer 2014;24:107-12. doi: 10.1097/IGC.0000000000000015.
  20. Zorzi R, Pescatori E. Metastasis of endometrial carcinoma to the tarsus. Chir Organi Mov 1982;68:727-30. Italian.
  21. Janis LR, Feldman EP. Metastatic adenocarcinoma of the calcaneus: Case report. J Foot Surg 1976;15:28-32.
  22. Litton GJ, Ward JH, Abbott TM, Williams HJ Jr. Isolated calcaneal metastasis in a patient with endometrial adenocarcinoma. Cancer 1991;67:1979- 83. doi: 10.1002/1097-0142(19910401)67:73.0.co;2-6.
  23. Cooper JK, Wong FL, Swenerton KD. Endometrial adenocarcinoma presenting as an isolated calcaneal metastasis. A rare entity with good prognosis. Cancer 1994;73:2779- 81. doi: 10.1002/1097-0142(19940601)73:113.0.co;2-u.
  24. Nishida Y, Hayata T, Miyakawa I. Metastatic calcaneal adenocarcinoma in a patient with uterine carcinoma. Int J Gynaecol Obstet 1994;45:287-8. doi: 10.1016/0020- 7292(94)90260-7.
  25. Petru E, Malleier M, Lax S, Lahousen M, Ehall R, Pickel H, et al. Solitary metastasis in the tarsus preceding the diagnosis of primary endometrial cancer. A case report. Eur J Gynaecol Oncol 1995;16:387-91.
  26. Clarke SJ, Smith TP. Metastatic endometrial carcinoma of the foot. A case report. J Am Podiatr Med Assoc 1996;86:331- 3. doi: 10.7547/87507315-86-7-331.
  27. Manolitsas TP, Fowler JM, Gahbauer RA, Gupta N. Pain in the foot: Calcaneal metastasis as the presenting feature of endometrial cancer. Obstet Gynecol 2002;100:1067-9. doi: 10.1016/s0029-7844(02)02015-x.
  28. Ali ZA, Wimhurst JA, Ali AA, Tempest ME, Edwards DJ. Endometrial cancer metastasis presenting as a grossly swollen toe. Int J Gynecol Cancer 2003;13:909-11. doi: 10.1111/j.1525-1438.2003.13630.x.
  29. Amiot RA, Wilson SE, Reznicek MJ, Webb BS. Endometrial carcinoma metastasis to the distal phalanx of the hallux: A case report. J Foot Ankle Surg 2005;44:462-5. doi: 10.1053/j. jfas.2005.07.014.
  30. Longo R, Gamelon-Benichou C, Elias-Matta C, Platini C, Eid N, Yacoubi M, et al. An unusual solitary metatarsal metastasis from an endometrioid endometrial adenocarcinoma. Am J Case Rep 2015;16:473-7. doi: 10.12659/ AJCR.893978.
  31. Onuba O. Pathological fracture of right tibia, an unusual presentation of endometrial carcinoma: A case report. Injury 1983;14:541-5. doi: 10.1016/0020-1383(83)90058-x.
  32. Armentano G, Bracco PL, Brizio R, Perelli G. Untreated endometrial adenocarcinoma: A case report. Eur J Gynaecol Oncol 1997;18:144-5.
  33. Loizzi V, Cormio G, Cuccovillo A, Fattizzi N, Selvaggi L. Two cases of endometrial cancer diagnosis associated with bone metastasis. Gynecol Obstet Invest 2006;61:49-52. doi: 10.1159/000088530.
  34. Ishibashi M, Fujiwaki R, Nakayama I, Miura H, Sawada K. Endometrial carcinosarcoma presenting as a tibial metastasis. Int J Clin Oncol 2007;12:305-8. doi: 10.1007/ s10147-006-0652-8.
  35. Kaya A, Olmezoglu A, Eren CS, Bayol U, Altay T, Karapinar L, et al. Solitary bone metastasis in the tibia as a presenting sign of endometrial adenocarcinoma: A case report and the review of the literature. Clin Exp Metastasis 2007;24:87-92. doi: 10.1007/s10585-007-9061-2.
  36. Pakos EE, Gartzonikas DN, Tsekeris PG, Xenakis TA. Solitary tibial osteolytic lesion. Case Rep Med 2009;2009:352085. doi: 10.1155/2009/352085.
  37. Artioli G, Cassaro M, Pedrini L, Borgato L, Corti L, Cappetta A, et al. Rare presentation of endometrial carcinoma with singular bone metastasis. Eur J Cancer Care (Engl) 2010;19:694-8. doi: 10.1111/j.1365-2354.2008.01045.x.
  38. Boukhar SA, Kaneshiro R, Schiller A, Terada K, TauchiNishi P. Tibial bone metastasis as an initial presentation of endometrial carcinoma diagnosed by fine-needle aspiration cytology: A case report and review of the literature. Cytojournal 2015;12:11. doi: 10.4103/1742-6413.157507.
  39. Beller U, Beckman EM, Bigelow B, Noumoff J. Early osseous metastasis of stage 1 endometrial carcinoma: Report of a case. Gynecol Oncol 198214:141-6. doi: 10.1016/0090- 8258(82)90061-0.
  40. Malicky ES, Kostic KJ, Jacob JH, Allen WC. Endometrial carcinoma presenting with an isolated osseous metastasis: A case report and review of the literature. Eur J Gynaecol Oncol 1997;18:492-4.
  41. Myriokefalitaki E, D'Costa D, Smith M, Ahmed AS. Primary bone metastasis as initial presentation of endometrial cancer (stage IVb). Arch Gynecol Obstet 2013;288:739-46. doi: 10.1007/s00404-013-2956-z.
  42. Rouchy R, Besson J, Grosieux P, Barraya PL. Osseous metastasis revealing endometrial cancer. Bull Fed Soc Gynecol Obstet Lang Fr 1967;19:352-3.
  43. Vanecko RM, Yao ST, Schmitz RL. Metastasis to the fibula from endometrial carcinoma. Report of 2 cases. Obstet Gynecol 1967;29:803-5.
  44. Dosoretz DE, Orr JW Jr, Salenius SA, Orr PF. Mandibular metastasis in a patient with endometrial cancer. Gynecol Oncol 1999;72:243-5. doi: 10.1006/gyno.1998.5223.
  45. Neto AG, Gupta D, Broaddus R, Malpica A. Endometrial endometrioid adenocarcinoma in a premenopausal woman presenting with metastasis to bone: A case report and review of the literature. Int J Gynecol Pathol 2002;21:281-4. doi: 10.1097/00004347-200207000-00013.
  46. Arnold J, Charters D, Perrin L. Prolonged survival time following initial presentation with bony metastasis in stage IVb endometrial carcinoma. Aust N Z J Obstet Gynaecol 2003;43:239-40. doi: 10.1046/j.0004-8666.2003.00050.x.
  47. Giannakopoulos CK, Kyriakidou GK, Toufexi GE. Bone metastasis as a presenting feature of endometrial adenocarcinoma: Case report and literature review. Eur J Gynaecol Oncol 2006;27:95-7.
  48. Uharcek P, Mlyncek M, Ravinger J. Endometrial adenocarcinoma presenting with an osseous metastasis. Gynecol Obstet Invest 2006;61:200-2. doi: 10.1159/000091402.
  49. Farooq MU, Chang HT. Intracranial and scalp metastasis of endometrial carcinoma. Med Sci Monit 2008;14:CS87-8.
  50. Shigemitsu A, Furukawa N, Koike N, Kobayashi H. Endometrial cancer diagnosed by the presence of bone metastasis and treated with zoledronic acid: A case report and review of the literature. Case Rep Oncol 2010;3:471-6. doi: 10.1159/000323150.
  51. Jiang GQ, Gao YN, Gao M, Zheng H, Yan X, Wang W, et al. Clinicopathological features and treatment of extremity bone metastasis in patients with endometrial carcinoma: A case report and review. Chin Med J (Engl) 2011;124:622-6.
  52. Gottwald L, Dukowicz A, Piekarski J, Pasz-Walczak G, Spych M, Kazmierczak-Lukaszewicz S, et al. Isolated metastasis to the foot as an extremely rare presenting feature of primary endometrial cancer. Arch Med Sci 2012;8:172-4. doi: 10.5114/aoms.2012.27299.
  53. Vizzielli G, Fanfani F, Costantini B, Gallotta V, Scambia G, Fagotti A. External hemipelvectomy as treatment for solitary coxofemoral metastasis from endometrial carcinoma: Case report and review of the literature. J Obstet Gynaecol Res 2012;38:892-8. doi: 10.1111/j.1447-0756.2011.01789.x.
  54. Bayraktutan U, Kantarci M, Yuce I, Sade R, Ogul H, Karaca L. Endometrial cancer metastasis mimicking spondylodiscitis and psoas abscess. Spine J 2016;16:e9-10. doi: 10.1016/j.spinee.2015.08.001.
  55. Doğer E, Çakiroğlu Y, Özdamar Ö, Ceylan Y, Köle E, Yücesoy I, et al. Bone metastasis in endometrial cancer: Evaluation of treatment approaches by factors affecting prognosis. Eur J Gynaecol Oncol 2016;37:407-16.
  56. Atik OŞ. Which articles do the editors prefer to publish? Jt Dis Relat Surg 2022;33:1-2. doi: 10.52312/jdrs.2022.57903.