Uterine Cancer pp 275-282 | Cite as

Therapeutic Options for Early-Stage Uterine Papillary Serous Carcinomas, Carcinosarcomas, and Clear-Cell and Mixed-Cell Histologies

  • Rachel Brightwell
  • Shashikant Lele


Type II endometrial carcinomas, accounting for 10–20 % of women diagnosed, are typically higher grade, diagnosed at a later stage of the disease, and with precursor lesions rarely identified. Type II endometrial carcinomas include uterine papillary serous carcinoma, carcinosarcoma, and clear-cell, mixed, mucinous, squamous, mesonephric, undifferentiated, and grade III endometrioid type carcinomas. Type II tumors are more aggressive, proposed to develop from endometrial intraepithelial carcinoma, a malignant transformation from atrophic endometrium or benign polyp epithelium, secondary to mutations in p53. Though uterine papillary serous carcinoma (UPSC) accounts for only 10 % of endometrial carcinomas, it accounts for nearly 40 % of endometrial cancer deaths [2]. Although vaginal bleeding is still the most common presenting symptom, it typically manifests in the UPSC patient at a much later stage, and other common presenting complaints include bloating and increased abdominal girth, early satiety, and other symptoms typical to epithelial ovarian cancer presentation.


Endometrial Cancer Endometrial Carcinoma Myometrial Invasion Common Present Complaint Malignant Mixed Mullerian Tumor 
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  1. 1.
    Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA, editors. SEER cancer statistics review, 1975–2010. Bethesda: National Cancer Institute., based on November 2012 SEER data submission, posted to the SEER web site, 2013.
  2. 2.
    Fader A, Santin AD, Gehrig PA. Early stage uterine serous carcinoma: management updates and genomic advances. Gynecol Oncol. 2013;129:244–50.CrossRefPubMedGoogle Scholar
  3. 3.
    Olawaiye AB, Rauh-Hain JA, Withian-Leitch M, Rueda B, Goodman AK, del Carmen MG. Utility of pre-operative CA-125 in the management of uterine papillary serous carcinoma. Gynecol Oncol. 2008;110:293–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Hoffman B, Schorge J, Schaffer J, Halvorson L, Bradshaw K, Cunningham F. Williams gynecology. 2nd ed. New York: McGraw-Hill; 2012.Google Scholar
  5. 5.
    Roelofsen T, Wiersma van Ham MA, van Tilburg JM. Pure compared with mixed serous endometrial carcinoma: two different entities? Obstet Gynecol. 2012;120:1371.PubMedGoogle Scholar
  6. 6.
    Murphy KT, Rotmensch J, Yamada SD, Mundt AJ. Outcome and patterns of failure in pathologic stages I-IV clear-cell carcinoma of the endometrium: implications for adjuvant radiation therapy. Int J Radiat Oncol Biol Phys. 2003;55:1272.CrossRefPubMedGoogle Scholar
  7. 7.
    Mutter GL, Lin MC, Fitzgerald JT, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst. 2000;92:924.CrossRefPubMedGoogle Scholar
  8. 8.
    Lax SF. Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Arch. 2004;444:213.CrossRefPubMedGoogle Scholar
  9. 9.
    Amant F, Moerman P, Neven P, et al. Endometrial cancer. Lancet. 2005;366:491.CrossRefPubMedGoogle Scholar
  10. 10.
    Shih I-M, Panuganti PK, Kuo KT, Mao TL, Kuhn E, Jones S, et al. Somatic mutations of PPP2R1A in ovarian and uterine carcinomas. Am J Pathol. 2011;178(4):1442–7.PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Khalifa MA, Mannel RS, Haraway SD, et al. Expression of EGFR, HER-2/neu, P53, and PCNA in endometrioid, serous papillary, and clear cell endometrial adenocarcinomas. Gynecol Oncol. 1994;53:84.CrossRefPubMedGoogle Scholar
  12. 12.
    Grushko TA, Filiaci VL, Mundt AJ, et al. An exploratory analysis of HER-2 amplification and overexpression in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2008;108:3.PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Geisen C, Moroy T. The oncogenic activity of cyclin E is not confined to Cdk2 activation alone but relies on several other, distinct functions of the protein. J Biol Chem. 2002;277(42):39909–18.CrossRefPubMedGoogle Scholar
  14. 14.
    ASTEC Study Group. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomized study. Lancet. 2009;373:125–36.CrossRefGoogle Scholar
  15. 15.
    Todo Y, Kato H, Kaneuchi M, Watari H, Takeda M, Sakuragi N. Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis. Lancet. 2010;375(9721):1165–72.CrossRefPubMedGoogle Scholar
  16. 16.
    Fader AN, Seamon LG, Escobar PF, Frasure HE, Havrilesky LA, Zanotti KM, et al. Minimally invasive surgery versus laparotomy in women with high grade endometrial cancer: a multi-site study performed at high volume cancer centers. Gynecol Oncol. 2012;126:180–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Leitao MM, et al. Impact of incorporating and algorithm that utilizes sentinel lymph node mapping during minimally invasive procedures on the detection of stage IIIC endometrial cancer. Gynecol Oncol. 2013;129:38–41.CrossRefPubMedGoogle Scholar
  18. 18.
    Fader AN, Boruta DM, Olawaiye AB, Gehrig PA. Uterine papillary serous cancer: epidemiology, pathogenesis and management. Curr Opin Obstet Gynecol. 2012;22:21–9.CrossRefGoogle Scholar
  19. 19.
    Kong A, Johnson N, Kitchener HC, Lawrie TA. Adjuvant radiotherapy for stage I endometrial cancer. Cochrane Database Syst Rev. 2012;4:CD003916.PubMedCentralPubMedGoogle Scholar
  20. 20.
    Tchabo NA, McCloskey S, Mashtare TL, Andrews C, Singh AK, Odunsi K, Lele S, Jaggernauth W. Treatment of early stage uterine papillary serous carcinoma at Roswell Park Cancer Institute, 1992–2006. Gynecol Oncol. 2009;115:249–56. PMID: 19692115.CrossRefPubMedGoogle Scholar
  21. 21.
    Fields AL, Einstein MH, Novetsky AP, Gebb J, Godberg GL. Pilot phase II trial of radiation “sandwiched” between combination paclitaxel/platinum chemotherapy in patients with uterine papillary serous carcinoma (UPSC). Gynecol Oncol. 2008;108:210–6.CrossRefGoogle Scholar
  22. 22.
    Kiess AP, Damast S, Makker V, Kollmeiyer MA, Gardner GJ, Aghajanian C, et al. Five-year outcomes of adjuvant carboplatin/paclitaxel chemotherapy and intravaginal radiation for stage I-II papillary serous endometrial cancer. Gynecol Oncol. 2012;127(2):321–5.CrossRefPubMedGoogle Scholar
  23. 23.
    Kernochan LE, Gracia RL. Carcinosarcoma (malignant mixed Mullerian tumor) of the uterus: advances in elucidation of biologic and clinical characteristics. J Natl Compr Canc Netw. 2009;7:550–6.PubMedGoogle Scholar
  24. 24.
    D’Angelo E, Prat J. Pathology of mixed mullerian tumors. Best Pract Res Clin Obstet Gynaecol. 2011;25:705–18.CrossRefPubMedGoogle Scholar
  25. 25.
    Rajshekar SK, Guruprasad B, Shakunthala PN, Rathod P, Devi U, Bafna UD. Malignant mixed Mullerian tumour of the uterus. Cancer. 2013;7:302.Google Scholar
  26. 26.
    Dave KS, Chauhan A, Bhansali R, et al. Uterine carcinosarcomas: 8-year single center experience of 25 cases. Indian J Med Paediatr Oncol. 2011;32:149.PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Sherman ME, Devesa SS. Analysis of racial differences in incidence, survival, and mortality for malignant tumors of the uterine corpus. Cancer. 2003;98:176.CrossRefPubMedGoogle Scholar
  28. 28.
    Salazar OM, Bonfiglio TA, Patten SF, et al. Uterine sarcomas: natural history, treatment and prognosis. Cancer. 1978;42:1152.CrossRefPubMedGoogle Scholar
  29. 29.
    Huang GS, Chiu LG, Gebb JS, et al. Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma. Gynecol Oncol. 2007;107:513.PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Nemani D, Mitra N, Guo M, Lin L. Assessing the effects of lymphadenectomy and radiation therapy in patients with uterine carcinosarcoma: a SEER analysis. Gynecol Oncol. 2008;111:82.CrossRefPubMedGoogle Scholar
  31. 31.
    Reed NS, Mangioni C, Malmström 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 55874). Eur J Cancer. 2008;44:808.CrossRefPubMedGoogle Scholar
  32. 32.
    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.CrossRefPubMedGoogle Scholar
  33. 33.
    Odunsi K, Moenke V, Tammela J, Ghamade S, Seago P, Driscoll D, Baker T, Marchetti D, Lele S. Efficacy of adjuvant CYVADIC chemotherapy in early stage uterine sarcomas: results of long term follow-up. Int J Gynecol Cancer. 2004;14(4):659–64.CrossRefPubMedGoogle Scholar
  34. 34.
    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;107:177.PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Cirisano Jr FD, 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.CrossRefPubMedGoogle Scholar
  36. 36.
    Thomas M, Mariani A, Wright JD, et al. Surgical management and adjuvant therapy for patients with uterine clear cell carcinoma: a multi-institutional review. Gynecol Oncol. 2008;108:293.CrossRefPubMedGoogle Scholar
  37. 37.
    Amant F, de la Rey M, Dorfling CM, et al. PTEN mutations in uterine sarcomas. Gynecol Oncol. 2002;85:165.CrossRefPubMedGoogle Scholar

Copyright information

© Springer India 2015

Authors and Affiliations

  1. 1.Department of Gynecologic OncologyRoswell Park Cancer InstituteBuffaloUSA

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