Abstract
Introduction: Carcinosarcomas are aggressive tumors that can arise from any part of the gynecological tractus. Uterine carcinosarcomas also called Malign Mixed Mullerian tumors, are de-differentiated carcinomas with sarcomatous and carcinomatous components arising from a single clone and are among high-risk endometrial carcinomas due to the similarity of epidemiology and clinical features. They account for less than 5% of all uterine cancers. In our study, we evaluated the histopathological and clinical features of our patients who were followed up with the diagnosis of uterine carcinosarcoma in our clinic in the light of the literature.
Methods: We performed a retrospective analysis of 13 patients who were diagnosed with pathologically confirmed uterine carcinosarcoma. Patients were followed up and treated in the tertiary university hospital Medical Oncology outpatient clinic between 2015 and 2020. Demographic data of the patients, complaints at presentation, stages of diagnosis, surgery performed, chemotherapy and radiotherapy information, risk factors were retrospectively reviewed. Patients with missing follow-up data were excluded from the study.
Results: 13 patients were diagnosed with uterine carcinosarcoma and their mean age was 70.4 (58-83). All of the patients were in the postmenopausal period. Abnormal uterine bleeding was the most frequent complaint. Obesity was significantly frequent and median BMI was 33.27 (12.49-44.44) despite the absence of pelvic radiotherapy and tamoxifen as etiologic factors. Staging surgery was applied to all of our patients. After surgery, 11 patients received adjuvant chemotherapy and the most common adjuvant treatment protocol was Carboplatin-Paclitaxel combination (54%).
Conclusion: Uterine carcinosarcomas are rare and very aggressive tumors. Despite intensive combined treatments, the 5-year estimated survival in all patients is around 35 % and it is a disease with a high recurrence rate in addition to poor survival. Currently recommended first option treatment approach is surgical staging. Chemotherapy and radiotherapy are recommended to increase survival after surgery. Advanced treatment strategies are needed in the management of uterine carcinosarcoma patients. For this purpose, prospective studies including more patients are needed.
References
- 1. Akahira J, Tokunaga H, Toyoshima M, et al. Prognoses and Prognostic Factors of Carcinosarcoma, Endometrial Stromal Sarcoma and Uterine Leiomyosarcoma: A Comparison with Uterine Endometrial Adenocarcinoma. Oncology 2006;71(5–6):333–40.
- 2. Fotiou S, Hatjieleftheriou G, Kyrousis G, Kokka F, Apostolikas N. Long-term tamoxifen treatment: a possible aetiological factor in the development of uterine carcinosarcoma: two case-reports and review of the literature. Anticancer Res. 2000 Jun;20(3B):2015–20.
- 3. Pothuri B, Ramondetta L, Eifel P, et al. Radiation-associated endometrial cancers are prognostically unfavorable tumors: A clinicopathologic comparison with 527 sporadic endometrial cancers. Gynecol Oncol. 2006 Dec;103(3):948–51.
- 4. Sherman ME, Devesa SS. Analysis of racial differences in incidence, survival, and mortality for malignant tumors of the uterine corpus. ancer. 2003 Jul 1;98(1):176–86.
- 5. Gadducci A, Cosio S, Romanini A, et al. The management of patients with uterine sarcoma: a debated clinical challenge. Crit Rev Oncol Hematol. 2008 Feb;65(2):129–42.
- 6. Felix AS, Stone RA, Bowser R, et al. Comparison of survival outcomes between patients with malignant mixed mullerian tumors and high-grade endometrioid, clear cell, and papillary serous endometrial cancers. Int J Gynecol cancer Off J Int Gynecol Cancer Soc. 2011 Jul;21(5):877–84.
- 7. Bansal N, Herzog TJ, Seshan VE, et al. Uterine carcinosarcomas and grade 3 endometrioid cancers: evidence for distinct tumor behavior. Obstet Gynecol. 2008 Jul;112(1):64–70.
- 8. Singh R. Review literature on uterine carcinosarcoma. J Cancer Res Ther. 2014;10(3):461–8.
- 9. Vorgias G, Fotiou S. The role of lymphadenectomy in uterine carcinosarcomas (malignant mixed mullerian tumours): a critical literature review. Arch Gynecol Obstet. 2010 Dec;282(6):659–64.
- 10. Denschlag D, Ulrich UA. Uterine carcinosarcomas - Diagnosis and management. Oncol Res Treat. 2018;41(11):675–9.
- 11. Makker V, Abu-Rustum NR, Alektiar KM, et al. A retrospective assessment of outcomes of chemotherapy-based versus radiation-only adjuvant treatment for completely resected stage I-IV uterine carcinosarcoma. Gynecol Oncol. 2008 Nov;111(2):249–54.
- 12. Abaid LN, Rettenmaier MA, Brown JV 3rd, et al. Sequential chemotherapy and radiotherapy as sandwich therapy for the treatment of high risk endometrial cancer. J Gynecol Oncol. 2012 Jan;23(1):22–7.
- 13. Kernochan LE, Garcia RL. Carcinosarcomas (malignant mixed Müllerian tumor) of the uterus: advances in elucidation of biologic and clinical characteristics. J Natl Compr Canc Netw. 2009 May;7(5):550–6; quiz 557.
- 14. Yamada SD , Burger RA , Brewster WR , et al. Pathologic variables and adjuvant therapy as predictors of recurrence and survival for patients with surgically evaluated carcinosarcoma of the uterus Cancer. 2000 Jun 15;88(12):2782-6.
- 15. Cantrell LA, Blank SV, Duska LR. Uterine carcinosarcoma: A review of the literature. Gynecol Oncol. 2015 Jun;137(3):581–8.
- 16. D’Angelo E, Prat J. Pathology of mixed Müllerian tumours. Best Pract Res Clin Obstet Gynaecol. 2011 Dec;25(6):705–18.
- 17. Uterine and Ovarian Carcinosarcomas: Do They Behave Similarly? J Obstet Gynaecol Can. 2017 Jul;39(7):559–63.
- 18. Berton-Rigaud D, Devouassoux-Shisheboran M, Ledermann JA, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for uterine and ovarian carcinosarcoma. Int J Gynecol cancer Off J Int Gynecol Cancer Soc. 2014 Nov;24(9 Suppl 3):S55-60.
- 19. Artioli G, Wabersich J, Ludwig K, Gardiman MP, Borgato L, Garbin F. Rare uterine cancer: carcinosarcomas. Review from histology to treatment. Crit Rev Oncol Hematol. 2015 Apr;94(1):98–104.
- 20. Huang GS, Chiu LG, Gebb JS, et al. Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma. Gynecol Oncol. 2007 Dec;107(3):513–7.
- 21. Thomakos N, Rodolakis A, Zagouri F, et al. Serum CA 125, CA 15-3, CEA, and CA 19-9: a prognostic factor for uterine carcinosarcomas? Arch Gynecol Obstet. 2013 Jan;287(1):97–102.
- 22. Tanner EJ, Leitao MMJ, Garg K, et al. The role of cytoreductive surgery for newly diagnosed advanced-stage uterine carcinosarcoma. Gynecol Oncol. 2011 Dec;123(3):548–52.
- 23. Major FJ, Blessing JA, Silverberg SG, et al. Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer. 1993 Feb;71(4 Suppl):1702–9.
- 24. Wolfson AH, Brady MF, Rocereto T, et al. A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Gynecol Oncol. 2007 Nov;107(2):177–85.
- 25. Gonzalez Bosquet J, Terstriep SA, Cliby WA, et al. The impact of multi-modal therapy on survival for uterine carcinosarcomas. Gynecol Oncol. 2010 Mar;116(3):419–23.
- 26. Omura GA, Blessing JA, Major F, et al. A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J Clin Oncol Off J Am Soc Clin Oncol. 1985 Sep;3(9):1240–5.
- 27. Homesley HD, Filiaci V, Markman M, et al. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Feb 10;25(5):526–31.
- 28. Powell MA, Filiaci VL, Hensley ML, et al. A randomized phase 3 trial of paclitaxel (P) plus carboplatin (C) versus paclitaxel plus ifosfamide (I) in chemotherapy-naive patients with stage I-IV, persistent or recurrent carcinosarcoma of the uterus or ovary: An NRG Oncology trial. JCO. 2019 May 20;37(15_suppl):5500–5500.
- 29. Chi DS, Mychalczak B, Saigo PE, et al. The role of whole-pelvic irradiation in the treatment of early-stage uterine carcinosarcoma. Gynecol Oncol. 1997 Jun;65(3):493–8.
- 30. Wright JD, Seshan VE, Shah M, et al. The role of radiation in improving survival for early-stage carcinosarcoma and leiomyosarcoma. Am J Obstet Gynecol. 2008 Nov;199(5):536.e1-8.
- 31. Secord AA, Havrilesky LJ, O’Malley DM, et al. A multicenter evaluation of sequential multimodality therapy and clinical outcome for the treatment of advanced endometrial cancer. Gynecol Oncol. 2009 Sep;114(3):442–7.
Abstract
Giriş: Karsinosarkomlar jinekolojik sistemin herhangi bir bölgesinden kaynaklanabilen agresif tümörlerdir. Malign mikst müllerian tümör olarak da adlandırılan uterin karsinosarkomlar tek klondan kaynaklanan sarkomatöz ve karsinomatöz komponentleri olan de-diferansiye karsinomlar olup epidemiyolojileri ve klinik davranışlarının benzerliğinden dolayı yüksek riskli endometrial karsinomlar arasında yer almaktadır ve tüm uterin kanserlerin %5’den azını oluşturmaktadır. Çalışmamızda, kliniğimizde uterin karsinosarkom tanısı ile takip ettiğimiz hastaların literatür eşliğinde histopatolojik ve klinik özelliklerini değerlendirdik.
Yöntemler: Çalışmaya 2015-2020 tarihleri arasında üçüncü basamak üniversite hastanesi Tıbbi Onkoloji polikliniğinde takip ve tedavi edilen patolojik olarak konfirme edilmiş, uterin karsinosarkom tanılı, 18 yaş üstü, toplam 13 hasta dahil edildi. Hastaların demografik verileri, başvuru şikayetleri, tanı evreleri, yapılan cerrahi, aldıkları kemoterapi ve radyoterapi bilgileri, risk faktörleri retrospektif olarak dosya taraması yapılarak elde edildi. Yeterli takipleri olmayan ve dosya verilerine ulaşılamayan hastalar çalışma dışı bırakıldı.
Bulgular: Kliniğimizde uterin karsinosarkom tanısı ile takip ettiğimiz 13 hastanın yaş ortalaması 70,4 (58-83) olup, tamamı postmenopozal dönemdeydi. Hastaların en sık başvuru şekli anormal vajinal kanamaydı. Etyolojik faktörler içinde pelvik radyoterapi ve tamoksifen kullanımı bulunmazken obezite sıklığı belirgindi. Hastaların ortalama vücut kitle indeksi (BMI) 33,27 (12,49-44,44) idi. Hastalarımızın tamamına evreleme cerrahisi uygulanmış olup, en sık kullanılan cerrahi total histerektomi, bilateralsalpingo-ooferektomi ve lenf nodu diseksiyonuydu. Bununla birlikte, 11 hastaya ise cerrahi sonrası adjuvan kemoterapi uygulanmış olup, en sık uygulanan adjuvan tedavi protokolü karboplatin-paklitaksel kombinasyonu idi (%54).
Sonuç: Uterin karsinosarkomlar nadir görülen ve oldukça agresif seyreden tümörlerdir. Yoğun kombine tedavilere rağmen tüm hastalarda 5 yıllık tahmini sağkalım yaklaşık %35 olup hastalık yüksek rekürrens oranına ve kötü sağkalıma sahiptir. Günümüzde önerilen tedavi yaklaşımı ilk seçenek olarak cerrahi evreleme, sonrasında adjuvan kemoterapi (KT) ve radyoterapi (RT) uygulamaları olmaktadır. Uterin karsinosarkom hastalarının yönetiminde gelişmiş tedavi stratejilerine ihtiyaç duyulmaktadır. Bu amaçla hasta sayısının fazla olduğu prospektif çalışmalara ihtiyaç vardır.
References
- 1. Akahira J, Tokunaga H, Toyoshima M, et al. Prognoses and Prognostic Factors of Carcinosarcoma, Endometrial Stromal Sarcoma and Uterine Leiomyosarcoma: A Comparison with Uterine Endometrial Adenocarcinoma. Oncology 2006;71(5–6):333–40.
- 2. Fotiou S, Hatjieleftheriou G, Kyrousis G, Kokka F, Apostolikas N. Long-term tamoxifen treatment: a possible aetiological factor in the development of uterine carcinosarcoma: two case-reports and review of the literature. Anticancer Res. 2000 Jun;20(3B):2015–20.
- 3. Pothuri B, Ramondetta L, Eifel P, et al. Radiation-associated endometrial cancers are prognostically unfavorable tumors: A clinicopathologic comparison with 527 sporadic endometrial cancers. Gynecol Oncol. 2006 Dec;103(3):948–51.
- 4. Sherman ME, Devesa SS. Analysis of racial differences in incidence, survival, and mortality for malignant tumors of the uterine corpus. ancer. 2003 Jul 1;98(1):176–86.
- 5. Gadducci A, Cosio S, Romanini A, et al. The management of patients with uterine sarcoma: a debated clinical challenge. Crit Rev Oncol Hematol. 2008 Feb;65(2):129–42.
- 6. Felix AS, Stone RA, Bowser R, et al. Comparison of survival outcomes between patients with malignant mixed mullerian tumors and high-grade endometrioid, clear cell, and papillary serous endometrial cancers. Int J Gynecol cancer Off J Int Gynecol Cancer Soc. 2011 Jul;21(5):877–84.
- 7. Bansal N, Herzog TJ, Seshan VE, et al. Uterine carcinosarcomas and grade 3 endometrioid cancers: evidence for distinct tumor behavior. Obstet Gynecol. 2008 Jul;112(1):64–70.
- 8. Singh R. Review literature on uterine carcinosarcoma. J Cancer Res Ther. 2014;10(3):461–8.
- 9. Vorgias G, Fotiou S. The role of lymphadenectomy in uterine carcinosarcomas (malignant mixed mullerian tumours): a critical literature review. Arch Gynecol Obstet. 2010 Dec;282(6):659–64.
- 10. Denschlag D, Ulrich UA. Uterine carcinosarcomas - Diagnosis and management. Oncol Res Treat. 2018;41(11):675–9.
- 11. Makker V, Abu-Rustum NR, Alektiar KM, et al. A retrospective assessment of outcomes of chemotherapy-based versus radiation-only adjuvant treatment for completely resected stage I-IV uterine carcinosarcoma. Gynecol Oncol. 2008 Nov;111(2):249–54.
- 12. Abaid LN, Rettenmaier MA, Brown JV 3rd, et al. Sequential chemotherapy and radiotherapy as sandwich therapy for the treatment of high risk endometrial cancer. J Gynecol Oncol. 2012 Jan;23(1):22–7.
- 13. Kernochan LE, Garcia RL. Carcinosarcomas (malignant mixed Müllerian tumor) of the uterus: advances in elucidation of biologic and clinical characteristics. J Natl Compr Canc Netw. 2009 May;7(5):550–6; quiz 557.
- 14. Yamada SD , Burger RA , Brewster WR , et al. Pathologic variables and adjuvant therapy as predictors of recurrence and survival for patients with surgically evaluated carcinosarcoma of the uterus Cancer. 2000 Jun 15;88(12):2782-6.
- 15. Cantrell LA, Blank SV, Duska LR. Uterine carcinosarcoma: A review of the literature. Gynecol Oncol. 2015 Jun;137(3):581–8.
- 16. D’Angelo E, Prat J. Pathology of mixed Müllerian tumours. Best Pract Res Clin Obstet Gynaecol. 2011 Dec;25(6):705–18.
- 17. Uterine and Ovarian Carcinosarcomas: Do They Behave Similarly? J Obstet Gynaecol Can. 2017 Jul;39(7):559–63.
- 18. Berton-Rigaud D, Devouassoux-Shisheboran M, Ledermann JA, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for uterine and ovarian carcinosarcoma. Int J Gynecol cancer Off J Int Gynecol Cancer Soc. 2014 Nov;24(9 Suppl 3):S55-60.
- 19. Artioli G, Wabersich J, Ludwig K, Gardiman MP, Borgato L, Garbin F. Rare uterine cancer: carcinosarcomas. Review from histology to treatment. Crit Rev Oncol Hematol. 2015 Apr;94(1):98–104.
- 20. Huang GS, Chiu LG, Gebb JS, et al. Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma. Gynecol Oncol. 2007 Dec;107(3):513–7.
- 21. Thomakos N, Rodolakis A, Zagouri F, et al. Serum CA 125, CA 15-3, CEA, and CA 19-9: a prognostic factor for uterine carcinosarcomas? Arch Gynecol Obstet. 2013 Jan;287(1):97–102.
- 22. Tanner EJ, Leitao MMJ, Garg K, et al. The role of cytoreductive surgery for newly diagnosed advanced-stage uterine carcinosarcoma. Gynecol Oncol. 2011 Dec;123(3):548–52.
- 23. Major FJ, Blessing JA, Silverberg SG, et al. Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer. 1993 Feb;71(4 Suppl):1702–9.
- 24. Wolfson AH, Brady MF, Rocereto T, et al. A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Gynecol Oncol. 2007 Nov;107(2):177–85.
- 25. Gonzalez Bosquet J, Terstriep SA, Cliby WA, et al. The impact of multi-modal therapy on survival for uterine carcinosarcomas. Gynecol Oncol. 2010 Mar;116(3):419–23.
- 26. Omura GA, Blessing JA, Major F, et al. A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J Clin Oncol Off J Am Soc Clin Oncol. 1985 Sep;3(9):1240–5.
- 27. Homesley HD, Filiaci V, Markman M, et al. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Feb 10;25(5):526–31.
- 28. Powell MA, Filiaci VL, Hensley ML, et al. A randomized phase 3 trial of paclitaxel (P) plus carboplatin (C) versus paclitaxel plus ifosfamide (I) in chemotherapy-naive patients with stage I-IV, persistent or recurrent carcinosarcoma of the uterus or ovary: An NRG Oncology trial. JCO. 2019 May 20;37(15_suppl):5500–5500.
- 29. Chi DS, Mychalczak B, Saigo PE, et al. The role of whole-pelvic irradiation in the treatment of early-stage uterine carcinosarcoma. Gynecol Oncol. 1997 Jun;65(3):493–8.
- 30. Wright JD, Seshan VE, Shah M, et al. The role of radiation in improving survival for early-stage carcinosarcoma and leiomyosarcoma. Am J Obstet Gynecol. 2008 Nov;199(5):536.e1-8.
- 31. Secord AA, Havrilesky LJ, O’Malley DM, et al. A multicenter evaluation of sequential multimodality therapy and clinical outcome for the treatment of advanced endometrial cancer. Gynecol Oncol. 2009 Sep;114(3):442–7.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | July 16, 2021 |
| Published in Issue | Year 2021 Volume: 2 Issue: 2 |
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