Uterine Cancer pp 193-216 | Cite as

Therapeutic Modalities in Early-Stage Uterine Papillary Serous Carcinomas, Carcinosarcomas, Clear-Cell and Mixed Histology Carcinomas

Building a Case for Combined Chemotherapy and Radiation
  • Nicholas P. Taylor
  • Matthew A. PowellEmail author
Part of the Current Clinical Oncology book series (CCO)


The entities covered in this chapter are uterine papillary serous carcinoma (UPSC), carcinosarcoma, and clear-cell carcinoma together with tumors of mixed histology. Overall, these represent 3–5% of all endometrial cancers but they are responsible for a significant percentage of endometrial cancer mortality. Recent strides in chemotherapy of some of these cancers offer hope that their addition, either alone or as part of combined modality treatment including radiation, will lead to improvements in survival.


Papillary serous Carcinosarcoma Clear cell Chemotherapy Chemo-radiation 


  1. 1.
    Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer Statistics, 2008. CA Cancer J Clin 2008;58(2):271–296.CrossRefGoogle Scholar
  2. 2.
    Rosenberg P, Blom R, Hogberg T, Simonsen E. Death rate and recurrence pattern among 841 clinical stage I endometrial cancer patients with special reference to uterine papillary serous carcinoma. Gynecol Oncol, 1993;51: 311–315.PubMedCrossRefGoogle Scholar
  3. 3.
    Lauchlan SC. Tubal (serous) carcinoma of the endometrium. Arch Pathol Lab Med, 1981;105: 615–618.PubMedGoogle Scholar
  4. 4.
    Hendrickson M, Ross J, Eifel P, Martinez A, Kempson R. Uterine papillary serous carcinoma: a highly malignant form of endometrial adenocarcinoma. Am J Surg Pathol, 1982;6: 93–108.PubMedCrossRefGoogle Scholar
  5. 5.
    Kato DT, Ferry JA, Goodman A, et al Uterine papillary serous carcinoma (UPSC): a clinicopathologic study of 30 cases. Gynecol Oncol, 1995;59: 384–389.PubMedCrossRefGoogle Scholar
  6. 6.
    Turner BC, Knisely JP, Kacinski BM, et al Effective treatment of stage I uterine papillary serous carcinoma with high dose-rate vaginal apex radiation (192Ir) and chemotherapy. Int J Radiat Oncol Biol Phys, 1998;40: 77–84.PubMedCrossRefGoogle Scholar
  7. 7.
    Cirisano FD, Jr, Robboy SJ, Dodge RK, et al The outcome of stage I-II clinically and surgically staged papillary serous and clear cell endometrial cancers when compared with endometrioid carcinoma. Gynecol Oncol, 2000;77: 55–65.PubMedCrossRefGoogle Scholar
  8. 8.
    Platz CE, Benda JA. Female genital tract cancer. Cancer, 1995;75: 270–294.PubMedCrossRefGoogle Scholar
  9. 9.
    Grice J, Ek M, Greer B, et al Uterine papillary serous carcinoma: evaluation of long-term survival in surgically staged patients. Gynecol Oncol, 1998;69: 69–73.PubMedCrossRefGoogle Scholar
  10. 10.
    Goff BA, Kato D, Schmidt RA, et al Uterine papillary serous carcinoma: patterns of metastatic spread. Gynecol Oncol, 1994;54: 264–268.PubMedCrossRefGoogle Scholar
  11. 11.
    Tay EH, Ward BG. The treatment of uterine papillary serous carcinoma (UPSC): are we doing the right thing? Int J Gynecol Cancer, 1999;9: 463–469.PubMedCrossRefGoogle Scholar
  12. 12.
    Bristow RE, Asrari F, Trimble EL, Montz FJ. Extended surgical staging for uterine papillary serous carcinoma: survival outcome of locoregional (Stage I-III) disease. Gynecol Oncol, 2001;81: 279–286.PubMedCrossRefGoogle Scholar
  13. 13.
    Abramovich D, Markman M, Kennedy A, Webster K, Belinson J. Serum CA-125 as a marker of disease activity in uterine papillary serous carcinoma. J Cancer Res Clin Oncol, 1999;125: 697–698.PubMedCrossRefGoogle Scholar
  14. 14.
    Boruta DM, 2nd, Gehrig PA, Groben PA, et al Uterine serous and grade 3 endometrioid carcinomas: is there a survival difference? Cancer, 2004;101: 2214–2221.PubMedCrossRefGoogle Scholar
  15. 15.
    Lax SF. Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Arch, 2004;444: 213–223.PubMedCrossRefGoogle Scholar
  16. 16.
    Slomovitz BM, Burke TW, Eifel PJ, et al Uterine papillary serous carcinoma (UPSC): a single institution review of 129 cases. Gynecol Oncol, 2003;91: 463–469.PubMedCrossRefGoogle Scholar
  17. 17.
    Chan JK, Loizzi V, Youssef M, et al Significance of comprehensive surgical staging in noninvasive papillary serous carcinoma of the endometrium. Gynecol Oncol, 2003;90: 181–185.PubMedCrossRefGoogle Scholar
  18. 18.
    Geisler JP, Geisler HE, Melton ME, Wiemann MC. What staging surgery should be performed on patients with uterine papillary serous carcinoma? Gynecol Oncol, 1999;74: 465–467.PubMedCrossRefGoogle Scholar
  19. 19.
    Carcangiu ML, Chambers JT. Uterine papillary serous carcinoma: a study on 108 cases with emphasis on the prognostic significance of associated endometrioid carcinoma, absence of invasion, and concomitant ovarian carcinoma. Gynecol Oncol, 1992;47: 298–305.PubMedCrossRefGoogle Scholar
  20. 20.
    Kelly MG, O’Malley DM, Hui P, et al Improved survival in surgical stage I patients with uterine papillary serous carcinoma (UPSC) treated with adjuvant platinum-based chemotherapy. Gynecol Oncol, 2005;98: 353–359.PubMedCrossRefGoogle Scholar
  21. 21.
    Lim P, Al Kushi A, Gilks B, Wong F, Aquino-Parsons C. Early stage uterine papillary serous carcinoma of the endometrium: effect of adjuvant whole abdominal radiotherapy and pathologic parameters on outcome. Cancer, 2001;91: 752–757.PubMedCrossRefGoogle Scholar
  22. 22.
    Sood BM, Jones J, Gupta S, et al Patterns of failure after the multimodality treatment of uterine papillary serous carcinoma. Int J Radiat Oncol Biol Phys, 2003;57: 208–216.PubMedCrossRefGoogle Scholar
  23. 23.
    Mehta N, Yamada SD, Rotmensch J, Mundt AJ. Outcome and pattern of failure in pathologic stage I-II papillary serous carcinoma of the endometrium: implications for adjuvant radiation therapy. Int J Radiat Oncol Biol Phys, 2003;57: 1004–1009.PubMedCrossRefGoogle Scholar
  24. 24.
    Keys HM, Roberts JA, Brunetto VL, et al A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol, 2004;92: 744–751.PubMedCrossRefGoogle Scholar
  25. 25.
    Huh WK, Powell M, Leath CA, 3rd, et al Uterine papillary serous carcinoma: comparisons of outcomes in surgical Stage I patients with and without adjuvant therapy. Gynecol Oncol, 2003;91: 470–475.PubMedCrossRefGoogle Scholar
  26. 26.
    Hamilton CA, Liou WS, Osann K, et al Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma. Int J Radiat Oncol Biol Phys, 2005;63: 839–844.PubMedCrossRefGoogle Scholar
  27. 27.
    Elit L, Kwon J, Bentley J, Trim K, Ackerman I, Carey M. Optimal management for surgically Stage 1 serous cancer of the uterus. Gynecol Oncol, 2004;92: 240–246.PubMedCrossRefGoogle Scholar
  28. 28.
    Dietrich CS, Modesitt SC, DePriest PD, et al The efficacy of adjuvant platinum-based chemotherapy in Stage I uterine papillary serous carcinoma (UPSC). Gynecol Oncol, 2005;99: 557–563.PubMedCrossRefGoogle Scholar
  29. 29.
    Ramondetta L, Burke TW, Levenback C, Bevers M, Bdurka-Bevers D, Gershenson DM. Treatment of uterine papillary serous carcinoma with paclitaxel. Gynecol Oncol, 2001;82: 156–161.PubMedCrossRefGoogle Scholar
  30. 30.
    Bancher-Todesca D, Neunteufel W, Williams KE, et al Influence of postoperative treatment on survival in patients with uterine papillary serous carcinoma. Gynecol Oncol, 1998;71: 344–347.PubMedCrossRefGoogle Scholar
  31. 31.
    Low JS, Wong EH, Tan HS, et al Adjuvant sequential chemotherapy and radiotherapy in uterine papillary serous carcinoma. Gynecol Oncol, 2005;97: 171–177.PubMedCrossRefGoogle Scholar
  32. 32.
    Fakiris AJ, Moore DH, Reddy SR, et al Intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy as adjuvant treatment for uterine papillary serous carcinoma and clear cell carcinoma: a phase II Hoosier Oncology Group (HOG 97-01) study. Gynecol Oncol, 2005;96: 818–823.PubMedCrossRefGoogle Scholar
  33. 33.
    Bitterman P, Chun B, Kurman RJ. The significance of epithelial differentiation in mixed mesodermal tumors of the uterus. A clinicopathologic and immunohistochemical study. Am J Surg Pathol, 1990;14: 317–328.PubMedCrossRefGoogle Scholar
  34. 34.
    Kounelis S, Jones MW, Papadaki H, Bakker A, Swalsky P, Finkelstein SD. Carcinosarcomas (malignant mixed mullerian tumors) of the female genital tract: comparative molecular analysis of epithelial and mesenchymal components. Hum Pathol, 1998;29: 82–87.PubMedCrossRefGoogle Scholar
  35. 35.
    Emoto M, Iwasaki H, Kikuchi M, Shirakawa K. Characteristics of cloned cells of mixed mullerian tumor of the human uterus. Carcinoma cells showing myogenic differentiation in vitro. Cancer, 1993;71: 3065–3075.PubMedCrossRefGoogle Scholar
  36. 36.
    Wada H, Enomoto T, Fujita M, et al Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors. Cancer Res, 1997;57: 5379–5385.PubMedGoogle Scholar
  37. 37.
    Fujii H, Yoshida M, Gong ZX, et al Frequent genetic heterogeneity in the clonal evolution of gynecological carcinosarcoma and its influence on phenotypic diversity. Cancer Res, 2000;60: 114–120.PubMedGoogle Scholar
  38. 38.
    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.PubMedCrossRefGoogle Scholar
  39. 39.
    Fleming WP, Peters WA, Kumar NB, Morley GW. Autopsy findings in patients with uterine sarcoma. Gynecol Oncol, 1984;19: 168–172.PubMedCrossRefGoogle Scholar
  40. 40.
    Amant F, Cadron I, Fuso L, et al Endometrial carcinosarcomas have a different prognosis and pattern of spread compared to high-risk epithelial endometrial cancer. Gynecol Oncol, 2005;98: 274–280.PubMedCrossRefGoogle Scholar
  41. 41.
    Brooks SE, Zhan M, Cote T, Baquet CR. Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989–1999. Gynecol Oncol, 2004;93: 204–208.PubMedCrossRefGoogle Scholar
  42. 42.
    Inthasorn P, Carter J, Valmadre S, Beale P, Russell P, Dalrymple C. Analysis of clinicopathologic factors in malignant mixed Mullerian tumors of the uterine corpus. Int J Gynecol Cancer, 2002;12: 348–353.PubMedCrossRefGoogle Scholar
  43. 43.
    McCluggage WG, Abdulkader M, Price JH, et al Uterine carcinosarcomas in patients receiving tamoxifen. A report of 19 cases. Int J Gynecol Cancer, 2000;10: 280–284.PubMedCrossRefGoogle Scholar
  44. 44.
    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.PubMedCrossRefGoogle Scholar
  45. 45.
    Nielsen SN, Podratz KC, Scheithauer BW, O’Brien PC. Clinicopathologic analysis of uterine malignant mixed mullerian tumors. Gynecol Oncol, 1989;34: 372–378.PubMedCrossRefGoogle Scholar
  46. 46.
    Ramondetta LM, Burke TW, Jhingran A, et al A phase II trial of cisplatin, ifosfamide, and mesna in patients with advanced or recurrent uterine malignant mixed mullerian tumors with evaluation of potential molecular targets. Gynecol Oncol, 2003;90: 529–536.PubMedCrossRefGoogle Scholar
  47. 47.
    Yamada SD, Burger RA, Brewster WR, Anton D, Kohler MF, Monk BJ. Pathologic variables and adjuvant therapy as predictors of recurrence and survival for patients with surgically evaluated carcinosarcoma of the uterus. Cancer, 2000;88: 2782–2786.PubMedCrossRefGoogle Scholar
  48. 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 of the uterus. Gynecol Oncol 2007; 107(2): 177–85.Google Scholar
  49. 49.
    Gerszten K, Faul C, Kounelis S, Huang Q, Kelley J, Jones MW. The impact of adjuvant radiotherapy on carcinosarcoma of the uterus. Gynecol Oncol, 1998;68: 8–13.PubMedCrossRefGoogle Scholar
  50. 50.
    Molpus KL, Redlin-Frazier S, Reed G, Burnett LS, Jones HW. Postoperative pelvic irradiation in early stage uterine mixed mullerian tumors. Eur J Gynaecol Oncol, 19: 541–546, 1998.PubMedGoogle Scholar
  51. 51.
    Knocke TH, Weitmann HD, Kucera H, Kolbl H, Pokrajac B, Potter R. Results of primary and adjuvant radiotherapy in the treatment of mixed Mullerian tumors of the corpus uteri. Gynecol Oncol, 1999;73: 389–395.PubMedCrossRefGoogle Scholar
  52. 52.
    Chi DS, Mychalczak B, Saigo PE, Rescigno J, Brown CL. The role of whole-pelvic irradiation in the treatment of early-stage uterine carcinosarcoma. Gynecol Oncol, 1997;65: 493–498.PubMedCrossRefGoogle Scholar
  53. 53.
    Le T. Adjuvant pelvic radiotherapy for uterine carcinosarcoma in a high risk population. Eur J Surg Oncol, 27: 282–285, 2001.PubMedCrossRefGoogle Scholar
  54. 54.
    Callister M, Ramondetta LM, Jhingran A, Burke TW, Eifel PJ. 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.PubMedCrossRefGoogle Scholar
  55. 55.
    Sartori E, Bazzurini L, Gadducci A, et al Carcinosarcoma of the uterus: a clinicopathological multicenter CTF study. Gynecol Oncol, 1997;67: 70–75.PubMedCrossRefGoogle Scholar
  56. 56.
    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, 1985;3: 1240–1245.PubMedGoogle Scholar
  57. 57.
    Sutton GP, Blessing JA, Rosenshein N, Photopulos G, DiSaia PJ. Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group study). Am J Obstet Gynecol, 1989;161: 309–312.PubMedGoogle Scholar
  58. 58.
    Sutton G, Brunetto VL, Kilgore L, et al A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: a Gynecologic Oncology Group study. Gynecol Oncol, 79: 147–153, 2000.PubMedCrossRefGoogle Scholar
  59. 59.
    Sutton G, Kauderer J, Carson LF, et al Adjuvant ifosfamide and cisplatin in patients with completely resected stage I or II carcinosarcomas (mixed mesodermal tumors) of the uterus: a Gynecologic Oncology Group study. Gynecol Oncol, 2005;96: 630–634.PubMedCrossRefGoogle Scholar
  60. 60.
    Resnik E, Chambers SK, Carcangiu ML, Kohorn EI, Schwartz PE, Chambers JT. A phase II study of etoposide, cisplatin, and doxorubicin chemotherapy in mixed mullerian tumors (MMT) of the uterus. Gynecol Oncol, 1995;56: 370–375.PubMedCrossRefGoogle Scholar
  61. 61.
    Curtin JP, Blessing JA, Soper JT, DeGeest K. Paclitaxel in the treatment of carcinosarcoma of the uterus: a Gynecologic Oncology Group study. Gynecol Oncol, 2001;83: 268–270.PubMedCrossRefGoogle Scholar
  62. 62.
    Miller DS, Blessing JA, Schilder J, Munkarah A, Lee YC. Phase II evaluation of topotecan in carcinosarcoma of the uterus: a Gynecologic Oncology Group study. Gynecol Oncol, 2005;98: 217–221.PubMedCrossRefGoogle Scholar
  63. 63.
    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(5):526–31.PubMedCrossRefGoogle Scholar
  64. 64.
    Toyoshima M, Akahira J, Matsunaga G, et al Clinical experience with combination paclitaxel and carboplatin therapy for advanced or recurrent carcinosarcoma of the uterus. Gynecol Oncol, 2004;94: 774–778.PubMedCrossRefGoogle Scholar
  65. 65.
    Odunsi K, Moneke V, Tammela J, et al Efficacy of adjuvant CYVADIC chemotherapy in early-stage uterine sarcomas: results of long-term follow-up. Int J Gynecol Cancer, 2004;14: 659–664.PubMedCrossRefGoogle Scholar
  66. 66.
    Kohorn EI, Schwartz PE, Chambers JT, Peschel RE, Kapp DS, Merino M. Adjuvant therapy in mixed mullerian tumors of the uterus. Gynecol Oncol, 1986;23: 212–221.PubMedCrossRefGoogle Scholar
  67. 67.
    Manolitsas TP, Wain GV, Williams KE, Freidlander M, Hacker NF. Multimodality therapy for patients with clinical Stage I and II malignant mixed Mullerian tumors of the uterus. Cancer, 2001;91: 1437–1443.PubMedCrossRefGoogle Scholar
  68. 68.
    Menczer J, Levy T, Piura B, et al A comparison between different postoperative treatment modalities of uterine carcinosarcoma. Gynecol Oncol, 2005;97: 166–170.PubMedCrossRefGoogle Scholar
  69. 69.
    Scully RE, Barlow JF. “Mesonephroma” of ovary. Tumor of Mullerian nature related to the endometrioid carcinoma. Cancer, 1967;20: 1405–1417.PubMedCrossRefGoogle Scholar
  70. 70.
    Kanbour-Shakir A, Tobon H. Primary clear cell carcinoma of the endometrium: a clinicopathologic study of 20 cases. Int J Gynecol Pathol, 1991;10: 67–78.PubMedCrossRefGoogle Scholar
  71. 71.
    Craighead PS, Sait K, Stuart GC, et al Management of aggressive histologic variants of endometrial carcinoma at the Tom Baker Cancer Centre between 1984 and 1994. Gynecol Oncol, 2000;77: 248–253.PubMedCrossRefGoogle Scholar
  72. 72.
    Cirisano FD Jr, Robboy SJ, Dodge RK, et al Epidemiologic and surgicopathologic findings of papillary serous and clear cell endometrial cancers when compared to endometrioid carcinoma. Gynecol Oncol, 1999;74: 385–394.PubMedCrossRefGoogle Scholar
  73. 73.
    Abeler VM, Kjorstad KE. Clear cell carcinoma of the endometrium: a histopathological and clinical study of 97 cases. Gynecol Oncol, 1991;40: 207–217.PubMedCrossRefGoogle Scholar
  74. 74.
    Carcangiu ML, Chambers JT. Early pathologic stage clear cell carcinoma and uterine papillary serous carcinoma of the endometrium: comparison of clinicopathologic features and survival. Int J Gynecol Pathol, 1995;14: 30–38.PubMedCrossRefGoogle Scholar
  75. 75.
    Creasman WT, Kohler MF, Odicino F, Maisonneuve P, Boyle P. Prognosis of papillary serous, clear cell, and grade 3 stage I carcinoma of the endometrium. Gynecol Oncol, 2004;95: 593–596.PubMedCrossRefGoogle Scholar
  76. 76.
    McMeekin DS, Filiaci VL, Thigpen JT, Gallion HH, Fleming GF, Rodgers WH. The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemo therapy trials: a Gynecologic Oncology Group study. Gynecol Oncol, 2007;106:16–22.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Division of Gynecologic Oncology, Department of Obstetrics and GynecologyWashington University School of MedicineSt. Louis

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