Gynäkologische Tumoren – Therapie und Prognosefaktoren uteriner Sarkome – Was ist neu?

Die uterinen Sarkome sind eine inhomogene Gruppe seltener, meist aggressiver Tumoren der Uterusmuskulatur, des endometrialen Stromas oder des uterinen Bindegewebes. Sie setzt sich aus histologisch verschiedenen Subtypen zusammen: zu den Sarkomen mesenchymalen Ursprungs gehören das Leiomyosarkom (LMS), low-grade und high-grade endometriale Stromasarkome (ESS) sowie das undifferenzierte Stromasarkom. Sarkome mit gemischt epithelial-mesenchymalem Ursprung sind das Adenosarkom und das Karzinosarkom. Die Inzidenz liegt bei 0,5–3,3 / 100 000 Frauen / Jahr [1] . Auf Grund der histologischen Diversität sind die empfohlenen Therapieansätze für jede Subgruppe spezifisch und werden im Folgenden einzeln beleuchtet.

• Literatur

• 1 Brooks SE, Zhan M, Cote T et al. Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989–1999. Gynecol Oncol 2004; 93: 204-208
• 2 DʼAngelo E, Prat J. Uterine sarcomas: a review. Gynecol Oncol 2010; 116: 131-139
• 3 Ali RH, Rouzbahman M. Endometrial stromal tumours revisited: an update based on the 2014 WHO classification. J Clin Pathol 2015; 68: 325-332
• 4 McCluggage WG. Malignant biphasic uterine tumours: carcinosarcomas or metaplastic carcinomas?. J Clin Pathol 2002; 55: 321-325
• 5 Lopez-Garcia MA, Palacios J. Pathologic and molecular features of uterine carcinosarcomas. Semin Diagn Pathol 2010; 27: 274-286
• 6 Liao Q, Wang J, Han J. Clinical and pathological analysis on 106 cases with uterine sarcoma. Zhonghua Fu Chan Ke Za Zhi 2001; 36: 104-107
• 7 Sreenan JJ, Hart WR. Carcinosarcomas of the female genital tract. A pathologic study of 29 metastatic tumors: further evidence for the dominant role of the epithelial component and the conversion theory of histogenesis. Am J Surg Pathol 1995; 19: 666-674
• 8 Zaloudek CJ. Mesenchymal tumors of the uterus. In: Kurman RJ, Hedrick Ellenson L, Ronnett BM , Hrsg. Blaustein‘s pathology of the female genital tract. New York, Dodrecht, Heidelberg, London: Springer; 2011
• 9 Sharma P, Kumar R, Singh H et al. Role of FDG PET-CT in detecting recurrence in patients with uterine sarcoma: comparison with conventional imaging. Nucl Med Commun 2012; 33: 185-190
• 10 Pelmus M, Penault-Llorca F, Guillou L et al. Prognostic factors in early-stage leiomyosarcoma of the uterus. Int J Gynecol Cancer 2009; 19: 385-390
• 11 Garg G, Shah JP, Kumar S et al. Ovarian and uterine carcinosarcomas: a comparative analysis of prognostic variables and survival outcomes. Int J Gynecol Cancer 2010; 20: 888-894
• 12 Brolmann H, Tanos V, Grimbizis G et al. Options on fibroid morcellation: a literature review. Gynecol Surg 2015; 12: 3-15
• 13 Einstein MH, Barakat RR, Chi DS et al. Management of uterine malignancy found incidentally after supracervical hysterectomy or uterine morcellation for presumed benign disease. Int J Gynecol Cancer 2008; 18: 1065-1070
• 14 Park JY, Kim DY, Suh DS et al. Prognostic factors and treatment outcomes of patients with uterine sarcoma: analysis of 127 patients at a single institution, 1989–2007. J Cancer Res Clin Oncol 2008; 134: 1277-1287
• 15 Park JY, Park SK, Kim DY et al. The impact of tumor morcellation during surgery on the prognosis of patients with apparently early uterine leiomyosarcoma. Gynecol Oncol 2011; 122: 255-259
• 16 Perri T, Korach J, Sadetzki S et al. Uterine leiomyosarcoma: does the primary surgical procedure matter?. Int J Gynecol Cancer 2009; 19: 257-260
• 17 Siedhoff MT, Wheeler SB, Rutstein SE et al. Laparoscopic hysterectomy with morcellation vs abdominal hysterectomy for presumed fibroid tumors in premenopausal women: a decision analysis. Am J Obstet Gynecol 2015; 212: 591 e1–8
• 18 Leitao MM, Sonoda Y, Brennan MF et al. Incidence of lymph node and ovarian metastases in leiomyosarcoma of the uterus. Gynecol Oncol 2003; 91: 209-212
• 19 Hensley ML, Ishill N, Soslow R et al. Adjuvant gemcitabine plus docetaxel for completely resected stages I-IV high grade uterine leiomyosarcoma: Results of a prospective study. Gynecol Oncol 2009; 112: 563-567
• 20 Hensley ML, Wathen JK, Maki RG et al. Adjuvant therapy for high-grade, uterus-limited leiomyosarcoma: results of a phase 2 trial (SARC 005). Cancer 2013; 119: 1555-1561
• 21 Pautier P, Floquet A, Gladieff L et al. A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group. Ann Oncol 2013; 24: 1099-1104
• 22 Reed NS, Mangioni C, Malmstrom H et al. Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55 874). Eur J Cancer 2008; 44: 808-818
• 23 Bernstein-Molho R, Grisaro D, Soyfer V et al. Metastatic uterine leiomyosarcomas: a single-institution experience. Int J Gynecol Cancer 2010; 20: 255-260
• 24 Giuntoli RL, Garrett-Mayer E, Bristow RE et al. Secondary cytoreduction in the management of recurrent uterine leiomyosarcoma. Gynecol Oncol 2007; 106: 82-88
• 25 Seddon B, Scurr M, Jones RL et al. A phase II trial to assess the activity of gemcitabine and docetaxel as first line chemotherapy treatment in patients with unresectable leiomyosarcoma. Clin Sarcoma Res 2015; 5: 13
• 26 Gadducci A, Guerrieri ME. Pharmacological treatment for uterine leiomyosarcomas. Expert Opin Pharmacother 2015; 16: 335-346
• 27 van der Graaf WT, Blay JY, Chawla SP et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2012; 379: 1879-1886
• 28 Pautier P, Floquet A, Chevreau C et al. Trabectedin in combination with doxorubicin for first-line treatment of advanced uterine or soft-tissue leiomyosarcoma (LMS-02): a non-randomised, multicentre, phase 2 trial. Lancet Oncol 2015; 16: 457-464
• 29 Hensley ML, Miller A, OʼMalley DM et al. Randomized phase III trial of gemcitabine plus docetaxel plus bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma: an NRG Oncology / Gynecologic Oncology Group study. J Clin Oncol 2015; 33: 1180-1185
• 30 Schöffski P, Maki RG, Italiano A. Randomized, open-label, multicenter, phase III study of eribulin versus dacarbazine in patients with leiomyosarcoma and adipocytic sarcoma. J Clin Oncol 2015; 33
• 31 Harter P, Sehouli J, Reuss A et al. Phase II study evaluating pegliposomal doxorubicin (PLD) and carboplatin combination chemotherapy in gynecologic sarcomas and mixed epithelial- mesenchymal tumors – A phase II protocol of the Arbeitsgemeinschaft Gynaekologische Onkologie Study Group (AGO-GYN 7). Int J Gynecol Cancer [in press]
• 32 Chang KL, Crabtree GS, Lim-Tan SK et al. Primary uterine endometrial stromal neoplasms. A clinicopathologic study of 117 cases. Am J Surg Pathol 1990; 14: 415-438
• 33 Barney B, Tward JD, Skidmore T et al. Does radiotherapy or lymphadenectomy improve survival in endometrial stromal sarcoma?. Int J Gynecol Cancer 2009; 19: 1232-1238
• 34 Chan JK, Kawar NM, Shin JY et al. Endometrial stromal sarcoma: a population-based analysis. Br J Cancer 2008; 99: 1210-1215
• 35 Bai H, Yang J, Cao D et al. Ovary and uterus-sparing procedures for low-grade endometrial stromal sarcoma: a retrospective study of 153 cases. Gynecol Oncol 2014; 132: 654-660
• 36 Chu MC, Mor G, Lim C et al. Low-grade endometrial stromal sarcoma: hormonal aspects. Gynecol Oncol 2003; 90: 170-176
• 37 Amant F, Coosemans A, Debiec-Rychter M et al. Clinical management of uterine sarcomas. Lancet Oncol 2009; 10: 1188-1198
• 38 Shah JP, Bryant CS, Kumar S et al. Lymphadenectomy and ovarian preservation in low-grade endometrial stromal sarcoma. Obstet Gynecol 2008; 112: 1102-1108
• 39 Gadducci A, Cosio S, Romanini A et al. The management of patients with uterine sarcoma: a debated clinical challenge. Crit Rev Oncol Hematol 2008; 65: 129-142
• 40 Malouf GG, Lhomme C, Duvillard P et al. Prognostic factors and outcome of undifferentiated endometrial sarcoma treated by multimodal therapy. Int J Gynaecol Obstet 2013; 122: 57-61
• 41 Tanner EJ, Garg K, Leitao Jr. MM. et al. High grade undifferentiated uterine sarcoma: surgery, treatment, and survival outcomes. Gynecol Oncol 2012; 127: 27-31
• 42 Schick U, Bolukbasi Y, Thariat J et al. Outcome and prognostic factors in endometrial stromal tumors: a rare cancer network study. Int J Radiat Oncol Biol Phys 2012; 82: e757-763
• 43 Yoon A, Park JY, Park JY et al. Prognostic factors and outcomes in endometrial stromal sarcoma with the 2009 FIGO staging system: a multicenter review of 114 cases. Gynecol Oncol 2014; 132: 70-75
• 44 Wu TI, Chou HH, Yeh CJ et al. Clinicopathologic parameters and immunohistochemical study of endometrial stromal sarcomas. Int J Gynecol Pathol 2013; 32: 482-492
• 45 Pautier P, Nam EJ, Provencher DM et al. Gynecologic Cancer InterGroup (GCIG) consensus review for high-grade undifferentiated sarcomas of the uterus. Int J Gynecol Cancer 2014; 24: S73-77
• 46 Della Badia C, Karini H. Endometrial stromal sarcoma diagnosed after uterine morcellation in laparoscopic supracervical hysterectomy. J Minim Invasive Gynecol 2010; 17: 791-793
• 47 Hendrickson MA. Mesenchymal tumors and related lesions. In: Tavassoli FA, Devilee P, Hrsg. Pathology and genetics of tumors of the breast and female genital organs. World Health Organization Classification of Tumours. Lyon: IARC Press; 2003: 233-249
• 48 Leath CA, Huh WK, Hyde Jr. J. et al. A multi-institutional review of outcomes of endometrial stromal sarcoma. Gynecol Oncol 2007; 105: 630-634
• 49 Fleming NA, Hopkins L, de Nanassy J et al. Mullerian adenosarcoma of the cervix in a 10-year-old girl: case report and review of the literature. J Pediatr Adolesc Gynecol 2009; 22: e45-51
• 50 Clement PB, Scully RE. Mullerian adenosarcoma of the uterus: a clinicopathologic analysis of 100 cases with a review of the literature. Hum Pathol 1990; 21: 363-81
• 51 Arend R, Bagaria M, Lewin SN et al. Long-term outcome and natural history of uterine adenosarcomas. Gynecol Oncol 2010; 119: 305-308
• 52 Bernard B, Clarke BA, Malowany JI et al. Uterine adenosarcomas: a dual-institution update on staging, prognosis and survival. Gynecol Oncol 2013; 131: 634-639
• 53 Friedlander ML, Covens A, Glasspool RM et al. Gynecologic Cancer InterGroup (GCIG) consensus review for mullerian adenosarcoma of the female genital tract. Int J Gynecol Cancer 2014; 24: S78-82
• 54 Krivak TC, Seidman JD, McBroom JW et al. Uterine adenosarcoma with sarcomatous overgrowth versus uterine carcinosarcoma: comparison of treatment and survival. Gynecol Oncol 2001; 83: 89-94
• 55 Tanner EJ, Long KC, Feffer JB et al. Parenchymal splenic metastasis is an independent negative predictor of overall survival in advanced ovarian, fallopian tube, and primary peritoneal cancer. Gynecol Oncol 2013; 128: 28-33
• 56 Aggarwal N, Bhargava R, Elishaev E. Uterine adenosarcomas: diagnostic use of the proliferation marker Ki-67 as an adjunct to morphologic diagnosis. Int J Gynecol Pathol 2012; 31: 447-452
• 57 Amant F, Schurmans K, Steenkiste E et al. Immunohistochemical determination of estrogen and progesterone receptor positivity in uterine adenosarcoma. Gynecol Oncol 2004; 93: 680-685
• 58 Amant F, Steenkiste E, Schurmans K et al. Immunohistochemical expression of CD10 antigen in uterine adenosarcoma. Int J Gynecol Cancer 2004; 14: 1118-1121
• 59 Soslow RA, Ali A, Oliva E. Mullerian adenosarcomas: an immunophenotypic analysis of 35 cases. Am J Surg Pathol 2008; 32: 1013-1021
• 60 Wittekind C, Oberschmid B. TNM classification of malignant tumors 2010: General aspects and amendments in the general section. Pathologe 2010; 31: 333-334 336–338
• 61 Horn LC, Schierle K, Schmidt D et al. Current TNM / FIGO classification for cervical and endometrial cancer as well as malignant mixed mullerian tumors. Facts and background. Pathologe 2011; 32: 239-243
• 62 Hedrick Ellenson L. Endometrial carcinoma. In: Kurman RJ, Hedrick Ellenson L, Ronnett BM , Hrsg. Blaustein‘s pathology of the female genital tract. New York, Dodrecht, Heidelberg, London: Springer; 2011
• 63 Amant F, de la Rey M, Dorfling CM et al. PTEN mutations in uterine sarcomas. Gynecol Oncol 2002; 85: 165-169
• 64 Bodner-Adler B, Bodner K, Obermair A et al. Prognostic parameters in carcinosarcomas of the uterus: a clinico-pathologic study. Anticancer Res 2001; 21: 3069-3074
• 65 Callister M, Ramondetta LM, Jhingran A et al. Malignant mixed Mullerian tumors of the uterus: analysis of patterns of failure, prognostic factors, and treatment outcome. Int J Radiat Oncol Biol Phys 2004; 58: 786-796
• 66 Dinh TA, Oliva EA, Fuller Jr. AF et al. The treatment of uterine leiomyosarcoma. Results from a 10-year experience (1990–1999) at the Massachusetts General Hospital. Gynecol Oncol 2004; 92: 648-652
• 67 Major FJ, Blessing JA, Silverberg SG et al. Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer 1993; 71: 1702-1709
• 68 Nordal RR, Kristensen GB, Stenwig AE et al. An evaluation of prognostic factors in uterine carcinosarcoma. Gynecol Oncol 1997; 67: 316-321
• 69 Sartori E, Bazzurini L, Gadducci A et al. Carcinosarcoma of the uterus: a clinicopathological multicenter CTF study. Gynecol Oncol 1997; 67: 70-75
• 70 Silverberg SG, Major FJ, Blessing JA et al. Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus. A Gynecologic Oncology Group pathologic study of 203 cases. Int J Gynecol Pathol 1990; 9: 1-19
• 71 Nemani D, Mitra N, Guo M et al. Assessing the effects of lymphadenectomy and radiation therapy in patients with uterine carcinosarcoma: a SEER analysis. Gynecol Oncol 2008; 111: 82-88
• 72 Park JY, Kim DY, Kim JH et al. The role of pelvic and / or para-aortic lymphadenectomy in surgical management of apparently early carcinosarcoma of uterus. Ann Surg Oncol 2010; 17: 861-868
• 73 Tanner EJ, Leitao Jr. MM, Garg K et al. The role of cytoreductive surgery for newly diagnosed advanced-stage uterine carcinosarcoma. Gynecol Oncol 2011; 123: 548-552
• 74 Cantrell LA, Havrilesky L, Moore DT et al. A multi-institutional cohort study of adjuvant therapy in stage I-II uterine carcinosarcoma. Gynecol Oncol 2012; 127: 22-26
• 75 Powell MA, Filiaci VL, Rose PG et al. Phase II evaluation of paclitaxel and carboplatin in the treatment of carcinosarcoma of the uterus: a Gynecologic Oncology Group study. J Clin Oncol 2010; 28: 2727-2731
• 76 Dickson EL, Vogel RI, Gehrig PA et al. A multi-institutional study of outcomes in stage I-III uterine carcinosarcoma. Gynecol Oncol 2015; 139: 275-282
• 77 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; 25: 526-531
• 78 du Bois A, Burges A, Meier W et al. Pegylated liposomal doxorubicin and carboplatin in advanced gynecologic tumors: a prospective phase I / II study of the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR). Ann Oncol 2006; 17: 93-96
• 79 Lacour RA, Euscher E, Atkinson EN et al. A phase II trial of paclitaxel and carboplatin in women with advanced or recurrent uterine carcinosarcoma. Int J Gynecol Cancer 2011; 21: 517-522