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Adjuvant therapy of uterine clear cell carcinoma: a review

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Abstract

Purpose

Uterine clear-cell carcinoma (UCCC) is a rare subset of type II endometrial carcinoma with a poor prognosis relative to the most common type of endometrioid carcinoma. Due to its rarity, there has been limited direct evidence of the efficacy of specific adjuvant therapy posthysterectomy in women with UCCC. We present a review of current literature regarding adjuvant therapy of uterine clear cell carcinoma.

Methods

We searched for English-language publications through Pubmed using a combination of the following key words: endometrial carcinoma, clear cell carcinoma, recurrence, prognosis, adjuvant therapy, radiation treatment and chemotherapy. Due to the rarity of UCCC, studies were not limited by design or number of patients.

Results

There is a paucity of randomized prospective controlled studies focusing on UCCC adjuvant therapy. Findings have largely been derived from retrospective studies of type II endometrial carcinomas or all endometrial cancers as a group. Very few retrospective studies were found to focus on UCCC adjuvant therapy, although certain larger studies did have subset analyses of UCCC patients.

Conclusions

For early stage disease, locoregional radiotherapy, especially vaginal brachytherapy, has evidence of efficacy. The therapeutic gain of radiotherapy may be further improved with the addition of systemic chemotherapy. Evidence for combined radiation therapy with systemic chemotherapy in women with advanced stage UCCC has remained debatable. UCCC-specific studies are needed to determine the best adjuvant therapy for UCCC without the confounding effects of USC and other endometrial cancers.

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References

  1. Siegel RL, Miller KD, Jemal A (2015) Cancer statistics. CA Cancer J Clin 65(1):5–29. doi:10.3322/caac.21254

    Article  PubMed  Google Scholar 

  2. Smith RS, Kapp DS, Chen Q, Teng NN (2000) Treatment of high-risk uterine cancer with whole abdominopelvic radiation therapy. Int J Radiat Oncol Biol Phys 48(3):767–778

    Article  CAS  PubMed  Google Scholar 

  3. Huang HJ, Tang YH, Chou HH, Yang LY, Chao A, Huang YT, Lin G, Liu FY, Chang TC, Lai CH (2014) Treatment failure in endometrial carcinoma. Int J Gynecol Cancer 24(5):885–893. doi:10.1097/IGC.0000000000000131

    Article  PubMed  Google Scholar 

  4. Cirisano FD Jr, Robboy SJ, Dodge RK, Bentley RC, Krigman HR, Synan IS, Soper JT, Clarke-Pearson DL (2000) The outcome of stage I–II clinically and surgically staged papillary serous and clear cell endometrial cancers when compared with endometrioid carcinoma. Gynecol Oncol 77(1):55–65. doi:10.1006/gyno.2000.5737

    Article  PubMed  Google Scholar 

  5. Murphy KT, Rotmensch J, Yamada SD, Mundt AJ (2003) 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 55(5):1272–1276

    Article  PubMed  Google Scholar 

  6. Carcangiu ML, Chambers JT (1995) Early pathologic stage clear cell carcinoma and uterine papillary serous carcinoma of the endometrium: comparison of clinicopathologic features and survival. Int J Gynecol Pathol 14(1):30–38

    Article  CAS  PubMed  Google Scholar 

  7. Abeler VM, Vergote IB, Kjorstad KE, Trope CG (1996) Clear cell carcinoma of the endometrium. Prognosis and metastatic pattern. Cancer 78(8):1740–1747

    Article  CAS  PubMed  Google Scholar 

  8. Christopherson WM, Alberhasky RC, Connelly PJ (1982) Carcinoma of the endometrium: I. a clinicopathologic study of clear-cell carcinoma and secretory carcinoma. Cancer 49(8):1511–1523

    Article  CAS  PubMed  Google Scholar 

  9. Mendivil A, Schuler KM, Gehrig PA (2009) Non-endometrioid adenocarcinoma of the uterine corpus: a review of selected histological subtypes. Cancer Control 16(1):46–52

    PubMed  Google Scholar 

  10. Fakiris AJ, Henderson M, Lo SS, Look KY, Cardenes HR (2010) Intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy as adjuvant treatment for uterine papillary serous carcinoma and clear cell carcinoma: the Indiana University experience. Brachytherapy 9(1):61–65. doi:10.1016/j.brachy.2008.10.005

    Article  PubMed  Google Scholar 

  11. Hsu KF, Chou HH, Huang CY, Fu HC, Chiang AJ, Tsai HW, Chen JR, Cheng WF, Ke YM, Chang CC, Chen TH, Lin SH, Ho CM (2014) Prognostic factors and treatment outcomes for patients with surgically staged uterine clear cell carcinoma focusing on the early stage: a Taiwanese gynecologic oncology group study. Gynecol Oncol 134(3):516–522. doi:10.1016/j.ygyno.2014.07.005

    Article  PubMed  Google Scholar 

  12. Olawaiye AB, Boruta DM 2nd (2009) Management of women with clear cell endometrial cancer: a society of gynecologic oncology (SGO) review. Gynecol Oncol 113(2):277–283. doi:10.1016/j.ygyno.2009.02.003

    Article  CAS  PubMed  Google Scholar 

  13. Hasegawa K, Nagao S, Yasuda M, Millan D, Viswanathan AN, Glasspool RM, Devouassoux-Shisheboran M, Covens A, Lorusso D, Kurzeder C, Kim JW, Gladieff L, Bryce J, Friedlander M, Fujiwara K (2014) Gynecologic cancer intergroup (GCIG) consensus review for clear cell carcinoma of the uterine corpus and cervix. Int J Gynecol Cancer 24(9 Suppl 3):S90–S95. doi:10.1097/IGC.0000000000000297

    Article  PubMed  Google Scholar 

  14. Glasspool RM, McNeish IA (2013) Clear cell carcinoma of ovary and uterus. Curr Oncol Rep 15(6):566–572. doi:10.1007/s11912-013-0346-0

    Article  CAS  PubMed  Google Scholar 

  15. Thomas M, Mariani A, Wright JD, Madarek EO, Powell MA, Mutch DG, Podratz KC, Dowdy SC (2008) Surgical management and adjuvant therapy for patients with uterine clear cell carcinoma: a multi-institutional review. Gynecol Oncol 108(2):293–297. doi:10.1016/j.ygyno.2007.11.008

    Article  CAS  PubMed  Google Scholar 

  16. Varughese J, Hui P, Lu L, Yu H, Schwartz PE (2011) Clear cell cancer of the uterine corpus: the association of clinicopathologic parameters and treatment on disease progression. J Oncol 2011:628084. doi:10.1155/2011/628084

    Article  PubMed Central  PubMed  Google Scholar 

  17. Kim A, Schreiber D, Rineer J, Choi K, Rotman M (2011) Impact of adjuvant external-beam radiation therapy in early-stage uterine papillary serous and clear cell carcinoma. Int J Radiat Oncol Biol Phys 81(4):e639–e644. doi:10.1016/j.ijrobp.2011.01.053

    Article  PubMed  Google Scholar 

  18. DuBeshter B, Estler K, Altobelli K, McDonald S, Glantz C, Angel C (2004) High-dose rate brachytherapy for Stage I/II papillary serous or clear cell endometrial cancer. Gynecol Oncol 94(2):383–386. doi:10.1016/j.ygyno.2004.05.009

    Article  PubMed  Google Scholar 

  19. Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA, Gynecologic Oncology Group S (2006) Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a gynecologic oncology group study. J Clin Oncol 24(1):36–44. doi:10.1200/JCO.2004.00.7617

  20. Sutton G, Axelrod JH, Bundy BN, Roy T, Homesley H, Lee RB, Gehrig PA, Zaino R (2006) Adjuvant whole abdominal irradiation in clinical stages I and II papillary serous or clear cell carcinoma of the endometrium: a phase II study of the gynecologic oncology group. Gynecol Oncol 100(2):349–354. doi:10.1016/j.ygyno.2005.08.037

    Article  PubMed  Google Scholar 

  21. Mahdi H, Lockhart D, Moselmi-Kebria M (2015) Prognostic impact of lymphadenectomy in uterine clear cell carcinoma. J Gynecol Oncol 26(2):134–140. doi:10.3802/jgo.2015.26.2.134

    Article  PubMed Central  PubMed  Google Scholar 

  22. National Comprehensive Cancer Network. Uterine Neoplasms (Version 2.2015). http://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed 20 July 2015

  23. McMeekin DS, Filiaci VL, Aghajanian C, Cho J, Kim JW, DiSilvestro PA, et al (2014) A randomized phase III trial of pelvic radiation therapy (PXRT) versus vaginal cuff brachytherapy followed by paclitaxel/carboplatin chemotherapy (VCB/C) in patients with high risk (HR), early stage endometrial cancer (EC): a gynecologic oncology group trial. Gynecol Oncol 134(2):438. doi:10.1016/j.ygyno.2014.07.078

    Article  Google Scholar 

  24. Leiden University Medical Center (2000) Randomized Phase III Trial Comparing Concurrent Chemoradiation and Adjuvant Chemotherapy with Pelvic Radiation Alone in High Risk and Advanced Stage Endometrial Carcinoma: PORTEC-3. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Available from:https://clinicaltrials.gov/ct2/show/NCT00411138. Accessed 1 Aug 2015 (NLM Identifier:NCT00411138)

  25. Mallipeddi P, Kapp DS, Teng NN (1993) Long-term survival with adjuvant whole abdominopelvic irradiation for uterine papillary serous carcinoma. Cancer 71(10):3076–3081

    Article  CAS  PubMed  Google Scholar 

  26. Potish RA (1989) Abdominal radiotherapy for cancer of the uterine cervix and endometrium. Int J Radiat Oncol Biol Phys 16(6):1453–1458

    Article  CAS  PubMed  Google Scholar 

  27. Frank AH, Tseng PC, Haffty BG, Papadopoulos DP, Kacinski BM, Dowling SW, Carcangiu ML, Kohorn EI, Chambers JT, Chambers SK et al (1991) Adjuvant whole-abdominal radiation therapy in uterine papillary serous carcinoma. Cancer 68(7):1516–1519

    Article  CAS  PubMed  Google Scholar 

  28. Yechieli R, Rasool N, Robbins JR, Cogan CM, Elshaikh MA (2013) Adjuvant radiation therapy for patients with type II endometrial carcinoma: impact on tumor recurrence and survival. Int J Gynecol Cancer 23(4):763–768. doi:10.1097/IGC.0b013e31828b15cb

    Article  PubMed  Google Scholar 

  29. Nout RA, Smit VT, Putter H, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Kroese MC, van Bunningen BN, Ansink AC, van Putten WL, Creutzberg CL, Group PS (2010) Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet 375(9717):816–823. doi:10.1016/S0140-6736(09)62163-2

  30. Fakiris AJ, Moore DH, Reddy SR, Look KY, Yiannoutsos CT, Randall ME, Cardenes HR, Hoosier Oncology G (2005) 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 96(3):818–823. doi:10.1016/j.ygyno.2004.11.050

    Article  CAS  PubMed  Google Scholar 

  31. Elshaikh MA, Vance S, Suri JS, Mahan M, Munkarah A (2014) Improved survival endpoints with adjuvant radiation treatment in patients with high-risk early-stage endometrial carcinoma. Int J Radiat Oncol Biol Phys 88(2):351–356. doi:10.1016/j.ijrobp.2013.11.003

    Article  PubMed  Google Scholar 

  32. Barney BM, Petersen IA, Mariani A, Dowdy SC, Bakkum-Gamez JN, Haddock MG (2013) The role of vaginal brachytherapy in the treatment of surgical stage I papillary serous or clear cell endometrial cancer. Int J Radiat Oncol Biol Phys 85(1):109–115. doi:10.1016/j.ijrobp.2012.03.011

    Article  PubMed  Google Scholar 

  33. Hogberg T, Signorelli M, de Oliveira CF, Fossati R, Lissoni AA, Sorbe B, Andersson H, Grenman S, Lundgren C, Rosenberg P, Boman K, Tholander B, Scambia G, Reed N, Cormio G, Tognon G, Clarke J, Sawicki T, Zola P, Kristensen G (2010) Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer—results from two randomised studies. Eur J Cancer 46(13):2422–2431. doi:10.1016/j.ejca.2010.06.002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Thigpen JT, Brady MF, Homesley HD, Malfetano J, DuBeshter B, Burger RA, Liao S (2004) Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a gynecologic oncology group study. J Clin Oncol 22(19):3902–3908. doi:10.1200/JCO.2004.02.088

    Article  CAS  PubMed  Google Scholar 

  35. Deppe G, Cohen CJ, Bruckner HW (1980) Treatment of advanced endometrial adenocarcinoma with cis-dichlorodiammine platinum (II) after intensive prior therapy. Gynecol Oncol 10(1):51–54

    Article  CAS  PubMed  Google Scholar 

  36. Lincoln S, Blessing JA, Lee RB, Rocereto TF (2003) Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: a gynecologic oncology group study. Gynecol Oncol 88(3):277–281

    Article  CAS  PubMed  Google Scholar 

  37. Gallion HH, Brunetto VL, Cibull M, Lentz SS, Reid G, Soper JT, Burger RA, Andersen W, Gynecologic Oncology Group S (2003) Randomized phase III trial of standard timed doxorubicin plus cisplatin versus circadian timed doxorubicin plus cisplatin in stage III and IV or recurrent endometrial carcinoma: a gynecologic oncology group study. J Clin Oncol 21(20):3808–3813. doi:10.1200/JCO.2003.10.083

  38. Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT (2004) Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a gynecologic oncology group study. J Clin Oncol 22(11):2159–2166. doi:10.1200/JCO.2004.07.184

    Article  CAS  PubMed  Google Scholar 

  39. Miller D, Filiaci V, Fleming G, Mannel R, Cohn D, Matsumoto T, Tewari K, DiSilvestro P, Pearl M, Zaino R (2012) Randomized phase III noninferiority trial of first line chemotherapy for metastatic or recurrent endometrial carcinoma: a gynecologic oncology group study. Gynecol Oncol 125(3):771–773. doi:10.1016/j.ygyno.2012.03.034

    Article  Google Scholar 

  40. Lee LJ, Bu P, Feltmate C, Viswanathan AN (2014) Adjuvant chemotherapy with external beamradiation therapy for high-grade, node-positive endometrial cancer. Int J Gynecol Cancer 24(8):1441–1448. doi:10.1097/IGC.0000000000000248

    Article  PubMed  Google Scholar 

  41. Gynecologic Oncology Group (2000) A randomized phase III trial of cisplatin and tumor volume directed irradiation followed by carboplatin and paclitaxel vs. carboplatin and paclitaxel for optimally debulked, advanced endometrial carcinoma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Available from:https://clinicaltrials.gov/ct2/show/NCT00942357. Accessed 5 Aug 2015 (NLM Identifier: NCT00942357)

  42. Elshaikh MA, Yashar CM, Wolfson AH, Cardenes HR, Erickson B, Jhingran A, Jolly S, Kidd E, Lee LJ, Mayr NA, Moore D, Rao GG, Small W, Jr., Varia MA, Wahl AO, Yuh W, Gaffney DK, Expert Panel on Radiation O-G (2014) ACR appropriateness criteria(R) advanced stage endometrial cancer. Am J Clin Oncol 37(4):391–396. doi:10.1097/COC.0000000000000098

  43. Homesley HD, Filiaci V, Gibbons SK, Long HJ, Cella D, Spirtos NM, Morris RT, DeGeest K, Lee R, Montag A (2009) A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: a gynecologic oncology group study. Gynecol Oncol 112(3):543–552. doi:10.1016/j.ygyno.2008.11.014

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Bruzzone M, Miglietta L, Franzone P, Gadducci A, Boccardo F (2004) Combined treatment with chemotherapy and radiotherapy in high-risk FIGO stage III–IV endometrial cancer patients. Gynecol Oncol 93(2):345–352. doi:10.1016/j.ygyno.2004.02.008

    Article  CAS  PubMed  Google Scholar 

  45. Greven K, Winter K, Underhill K, Fontenesci J, Cooper J, Burke T (2006) Final analysis of RTOG 9708: adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer. Gynecol Oncol 103(1):155–159. doi:10.1016/j.ygyno.2006.02.007

    Article  CAS  PubMed  Google Scholar 

  46. Secord AA, Geller MA, Broadwater G, Holloway R, Shuler K, Dao NY, Gehrig PA, O’Malley DM, Finkler N, Havrilesky LJ (2013) A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer. Gynecol Oncol 128(1):65–70. doi:10.1016/j.ygyno.2012.10.010

    Article  CAS  PubMed  Google Scholar 

  47. Fadare O, Renshaw IL, Liang SX (2012) Does the loss of ARID1A (BAF-250a) expression in endometrial clear cell carcinomas have any clinicopathologic significance? A pilot assessment. J Cancer 3:129–136. doi:10.7150/jca.4140

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. An HJ, Logani S, Isacson C, Ellenson LH (2004) Molecular characterization of uterine clear cell carcinoma. Mod Pathol 17(5):530–537. doi:10.1038/modpathol.3800057

    Article  CAS  PubMed  Google Scholar 

  49. Hoang LN, McConechy MK, Meng B, McIntyre JB, Ewanowich C, Gilks CB, Huntsman DG, Kobel M, Lee CH (2015) Targeted mutation analysis of endometrial clear cell carcinoma. Histopathology 66(5):664–674. doi:10.1111/his.12581

    Article  PubMed  Google Scholar 

  50. Binder PS, Prat J, Mutch DG (2015) Molecular staging of gynecological cancer: what is the future? Best Pract Res Clin Obstet Gynaecol. doi:10.1016/j.bpobgyn.2015.01.008

    PubMed  Google Scholar 

  51. Han G, Soslow RA, Wethington S, Levine DA, Bogomolniy F, Clement PB, Kobel M, Gilks B, DeLair D (2015) Endometrial carcinomas with clear cells: a study of a heterogeneous group of tumors including interobserver variability, mutation analysis, and immunohistochemistry with HNF-1beta. Int J Gynecol Pathol 34(4):323–333. doi:10.1097/PGP.0000000000000162

    Article  CAS  PubMed  Google Scholar 

  52. Ashour AA, Verschraegen CF, Kudelka AP, Kavanagh JJ (1997) Paraneoplastic syndromes of gynecologic neoplasms. J Clin Oncol 15(3):1272–1282

    CAS  PubMed  Google Scholar 

  53. Matsuura Y, Robertson G, Marsden DE, Kim SN, Gebski V, Hacker NF (2007) Thromboembolic complications in patients with clear cell carcinoma of the ovary. Gynecol Oncol 104(2):406–410. doi:10.1016/j.ygyno.2006.08.026

    Article  PubMed  Google Scholar 

  54. Toyoda M, Satoh T, Takano K, Sato NO, Oki A, Tsunoda H, Yoshikawa H (2005) Successful diagnosis of thromboembolism before surgery in a woman with clear cell adenocarcinoma of the endometrium. Int J Clin Oncol 10(6):444–446. doi:10.1007/s10147-005-0517-6

    Article  PubMed  Google Scholar 

  55. Matsuo K, Yessaian AA, Lin YG, Pham HQ, Muderspach LI, Liebman HA, Morrow CP, Roman LD (2013) Predictive model of venous thromboembolism in endometrial cancer. Gynecol Oncol 128(3):544–551. doi:10.1016/j.ygyno.2012.12.014

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI, 48202, USA

    Yiqing Xu & Mohamed A. Elshaikh

  2. Division of Gynecologic Oncology, Department of Women’ Health Services, Henry Ford Hospital, Detroit, MI, 48202, USA

    Rabbie K. Hanna

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  1. Yiqing Xu
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  2. Rabbie K. Hanna
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Correspondence to Mohamed A. Elshaikh.

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Xu, Y., Hanna, R.K. & Elshaikh, M.A. Adjuvant therapy of uterine clear cell carcinoma: a review. Arch Gynecol Obstet 293, 485–492 (2016). https://doi.org/10.1007/s00404-015-3973-x

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