Skip to main content
SpringerLink
Log in

Current Concepts in Radiation Therapy for Early-Stage Endometrial Cancer

  • Review Article
  • Published:
Indian Journal of Gynecologic Oncology Aims and scope Submit manuscript

Abstract

Purpose

The present article aims to review current management for early-stage endometrioid carcinomas with a specific focus on adjuvant radiotherapy.

Methods

A comprehensive literature review was conducted regarding management of early-stage endometrioid-type endometrial cancers. Abstracted information included risk of relapse, treatment approach, and morbidity from treatment.

Results

A majority of low-risk patients are safely managed with observation, with vaginal cuff brachytherapy (VCBT) reserved for those with multiple other risk factors. Intermediate-risk patients are a heterogeneous group with a variable definition; previous trials have established that VCBT alone is suitable for most patients to avoid morbidity of pelvic external beam radiotherapy (EBRT). High- and high-intermediate risk patients warrant pelvic EBRT ± VCBT with or without sequential chemotherapy. Continued controversy exists regarding the optimal VCBT fractionation regimen, with suggestion that higher dose/fraction regimens may lead to increased vaginal toxicity. Intensity-modulated radiotherapy is being investigated in an effort to reduce late toxicities. Advanced brachytherapy techniques such as image-guided brachytherapy have improved treatment of salvage and medically inoperable patients.

Conclusions

Identification of risk groups and toxicity reduction through either appropriate radiotherapy techniques or advanced techniques has enabled optimization of adjuvant management for early-stage endometrial cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.

    Article  PubMed  Google Scholar 

  3. Klopp A, Smith BD, Alektiar K, et al. The role of postoperative radiation therapy for endometrial cancer: executive summary of an American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol. 2014;4(3):137–44.

    Article  PubMed  Google Scholar 

  4. Burke WM, Orr J, Leitao M, et al. Endometrial cancer: a review and current management strategies: part II. Gynecol Oncol. 2014;134(2):393–402.

    Article  PubMed  Google Scholar 

  5. Small W, Beriwal S, Demanes DJ, et al. American Brachytherapy Society consensus guidelines for adjuvant vaginal cuff brachytherapy after hysterectomy. Brachytherapy. 2012;11(1):58–67.

    Article  PubMed  Google Scholar 

  6. Creasman WT, Morrow CP, Bundy BN, et al. Surgical pathologic spread patterns of endometrial cancer: a Gynecologic Oncology Group Study. Cancer. 1987;60:2035–41.

    Article  CAS  PubMed  Google Scholar 

  7. Creasman WT, Odicino F, Maisonneuve P, et al. Carcinoma of the corpus uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006;95(S1):S105–43.

    Article  PubMed  Google Scholar 

  8. Creutzberg CL, Nout RA, Lybeert ML, et al. Fifteen-year radiotherapy outcome of the randomized PORTEC-1 trial for endometrial carcinoma. Int J Radiat Oncol Biol Phys. 2011;81(4):631–8.

    Article  Google Scholar 

  9. Guntupalli SR, Zighelboim I, Kizer NT, et al. Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer. Gynecol Oncol. 2012;124(1):31–5.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Abu-rustum NR, Zhou Q, Gomez JD, et al. A nomogram for predicting overall survival of women with endometrial cancer following primary therapy: toward improving individualized cancer care. Gynecol Oncol. 2010;116(3):399–403.

    Article  CAS  PubMed  Google Scholar 

  11. Kondalsamy-Chennakesavan S, Yu C, Kattan MW, et al. Nomograms to predict isolated loco-regional or distant recurrence among women with uterine cancer. Gynecol Oncol. 2012;125(3):520–5.

    Article  PubMed  Google Scholar 

  12. Creutzberg CL, van Stiphout RG, Nout RA, et al. Nomograms for prediction of outcome with or without adjuvant radiation therapy for patients with endometrial cancer: a pooled analysis of PORTEC-1 and PORTEC-2 trials. Int J Radiat Oncol Biol Phys. 2015;91(3):530–9.

    Article  PubMed  Google Scholar 

  13. Straughn JM Jr, Huh WK, Kelly FJ, et al. Conservative management of stage I endometrial carcinoma after surgical staging. Gynecol Oncol. 2002;84(2):194–200.

    Article  PubMed  Google Scholar 

  14. Sorbe B, Nordström B, Mäenpää J, et al. Intravaginal brachytherapy in FIGO stage I low-risk endometrial cancer: a controlled randomized study. Int J Gynecol Cancer. 2009;19(5):873–8.

    Article  PubMed  Google Scholar 

  15. Mariani A, Dowdy SC, Keeney GL, et al. Predictors of vaginal relapse in stage I endometrial cancer. Gynecol Oncol. 2005;97:820–7.

    Article  PubMed  Google Scholar 

  16. 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(3):744–51.

    Article  PubMed  Google Scholar 

  17. Nout RA, Van de Poll-Franse LV, Lybeert ML, et al. Long-term outcome and quality of life of patients with endometrial carcinoma treated with or without pelvic radiotherapy in the post operative radiation therapy in endometrial carcinoma 1 (PORTEC-1) trial. J Clin Oncol. 2011;29(13):1692–700.

    Article  PubMed  Google Scholar 

  18. Scholten AN, Van putten WL, Beerman H, et al. Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys. 2005;63(3):834–8.

    Article  PubMed  Google Scholar 

  19. Blake P, Swart AM, Orton J, et al. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet. 2009;373(9658):137–46.

    Article  CAS  PubMed  Google Scholar 

  20. Aalders J, Abeler V, Kolstad P, Onsrud M. Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol. 1980;56(4):419–27.

    CAS  PubMed  Google Scholar 

  21. Sorbe B, Horvath G, Andersson H, Boman K, Lundgren C, Pettersson B. External pelvic and vaginal irradiation versus vaginal irradiation alone as postoperative therapy in medium-risk endometrial carcinoma–a prospective randomized study. Int J Radiat Oncol Biol Phys. 2012;82(3):1249–55.

    Article  PubMed  Google Scholar 

  22. Nout RA, Smit VT, Putter H, et al. 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. 2010;375(9717):816–23.

    Article  CAS  PubMed  Google Scholar 

  23. Onsrud M, Cvancarova M, Hellebust TP, Tropé CG, Kristensen GB, Lindemann K. Long-term outcomes after pelvic radiation for early stage endometrial cancer. J Clin Oncol. 2013;31(31):3951–6.

    Article  PubMed  Google Scholar 

  24. Wiltink LM, Nout RA, Fiocco M, et al. No increased risk of second cancer after radiotherapy in patients treated for rectal or endometrial cancer in the randomized TME, PORTEC-1, and PORTEC-2 trials. J Clin Oncol. 2015;33(15):1640–6.

    Article  PubMed  Google Scholar 

  25. Creutzberg CL, Van putten WL, Koper PC, et al. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol. 2003;89(2):201–9.

    Article  PubMed  Google Scholar 

  26. Creutzberg CL, Van putten WL, Wárlám-rodenhuis CC, et al. Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial. J Clin Oncol. 2004;22(7):1234–41.

    Article  PubMed  Google Scholar 

  27. Cohn DE, Horowitz NS, Mutch DG, Kim SM, Manolitsas T, Fowler JM. Should the presence of lymphovascular space involvement be used to assign patients to adjuvant therapy following hysterectomy for unstaged endometrial cancer? Gynecol Oncol. 2002;87(3):243–6.

    Article  PubMed  Google Scholar 

  28. Susumu N, Sagae S, Udagawa Y, et al. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Gynecol Oncol. 2008;108(1):226–33.

    Article  CAS  PubMed  Google Scholar 

  29. Landrum LM, Nugent EK, Zuna RE, et al. Phase II trial of vaginal cuff brachytherapy followed by chemotherapy in early stage endometrial cancer patients with high-intermediate risk factors. Gynecol Oncol. 2014;132(1):50–4.

    Article  PubMed  Google Scholar 

  30. McMeekin DS, Filiaci VL, Aghajanian C, et al. 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. 2014;134(2):438.

    Article  Google Scholar 

  31. 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(5):1065–70.

    Article  CAS  PubMed  Google Scholar 

  32. Ayhan A, Kart C, Guven S, Boynukalin K, Kucukali T. The role of reoperation in the management of endometrial carcinoma found in simple hysterectomy. J Surg Oncol. 2006;93(5):373–8.

    Article  PubMed  Google Scholar 

  33. Sau S, Ghosh S, Mitra S, et al. A retrospective six years analysis of survival and late morbidity of post-operative gynaecological malignancy treated with external radiotherapy followed by brachytherapy in Medical College & Hospitals, Kolkata. J Obstet Gynaecol India. 2013;63(2):128–34.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Bahng AY, Dagan A, Bruner DW, Lin LL. Determination of prognostic factors for vaginal mucosal toxicity associated with intravaginal high-dose rate brachytherapy in patients with endometrial cancer. Int J Radiat Oncol Biol Phys. 2012;82(2):667–73.

    Article  PubMed  Google Scholar 

  35. Sorbe B, Straumits A, Karlsso L. Intravaginal high-dose-rate brachytherapy for stage I endometrial cancer: a randomized study of two dose-per-fraction levels. Int J Radiat Oncol Biol Phys. 2005;62:1385–9.

    Article  PubMed  Google Scholar 

  36. Sorbe B, Smeds AC. Postoperative vaginal irradiation with high dose rate afterloading technique in endometrial carcinoma stage I. Int J Radiat Oncol Biol Phys. 1990;18:305–14.

    Article  CAS  PubMed  Google Scholar 

  37. Nori D, Merimsky O, Batata M, Caputo T. Postoperative high dose-rate intravaginal brachytherapy combined with external irradiation for early stage endometrial cancer: a long-term follow-up. Int J Radiat Oncol Biol Phys. 1994;30:831–7.

    Article  CAS  PubMed  Google Scholar 

  38. Beriwal S, Jain SK, Heron DE, et al. Clinical outcome with adjuvant treatment of endometrial carcinoma using intensity-modulated radiation therapy. Gynecol Oncol. 2006;102(2):195–9.

    Article  PubMed  Google Scholar 

  39. Creutzberg CL, van Putten WL, Koper PC, et al. The morbidity of treatment for patients with stage I endometrial cancer: results from a randomized trial. Int J Radiat Oncol Biol Phys. 2001;51(5):1246–55.

    Article  CAS  PubMed  Google Scholar 

  40. Roeske JC, Lugan A, Rotmensch J, et al. Intensity-modulated whole pelvic radiation therapy in patients with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2000;48(5):1613–21.

    Article  CAS  PubMed  Google Scholar 

  41. Heron DE, Gerszten K, Selvaraj RN, et al. Conventional 3D conformal versus intensity-modulated radiotherapy for the adjuvant treatment of gynecologic malignancies: A comparative dosimetric study of dose-volume histograms. Gynecol Oncol. 2003;91(1):39–45.

    Article  CAS  PubMed  Google Scholar 

  42. Mell LK, Tiryaki H, Ahn KH, et al. Dosimetric comparison of bone marrow sparing intensity-modulated radiotherapy versus conventional techniques for treatment of cervical cancer. Int J Radiat Oncol Biol Phys. 2008;71(5):1504–10.

    Article  PubMed  Google Scholar 

  43. Yang B, Zhu L, Cheng H, et al. Dosimetric comparison of intensity modulated radiotherapy and three-dimensional conformal radiotherapy in patients with gynecologic malignancies: a systematic review and meta-analysis. Radiat Oncol. 2012;7:197.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Shih KK, Milgrom SA, Abu-Rustum NR, et al. Postoperative pelvic intensity-modulated radiotherapy in high risk endometrial cancer. Gynecol Oncol. 2013;128(3):535–9.

    Article  PubMed  Google Scholar 

  45. Jhingran A, Winter K, Portelance L, et al. Efficacy and safety of IMRT after surgery in patients with endometrial cancer: RTOG 0418 phase II study. Int J Radiat Oncol Biol Phys. 2011;81(2):S45.

    Article  Google Scholar 

  46. Klopp AH, Moughan J, Portelance L, et al. Hematologic toxicity in RTOG 0418: a phase 2 study of postoperative IMRT for gynecologic cancer. Int J Radiat Oncol Biol Phys. 2013;86(1):83–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Jhingran A, Burke TW, Eifel PJ. Definitive radiotherapy for patients with isolated vaginal recurrence of endometrial carcinoma after hysterectomy. Int J Radiat Oncol Biol Phys. 2003;56:1368–72.

    Article  Google Scholar 

  48. Sears JD, Greven K, Hoen HM, Randall ME. Prognostic factors and treatment outcome for patients with locally recurrent endometrial carcinoma. Cancer. 1994;74:1303–8.

    Article  CAS  PubMed  Google Scholar 

  49. Hoekstra CJ, Koper PC, van Putten WL. Recurrent endometrial adenocarcinoma after surgery alone: prognostic factors and treatment. Radiother Oncol. 1993;27:164–6.

    Article  CAS  PubMed  Google Scholar 

  50. Wylie J, Irwin C, Pintillie M, et al. Results of radical radiotherapy for recurrent endometrial cancer. Gynecol Oncol. 2000;77:66–72.

    Article  CAS  PubMed  Google Scholar 

  51. Curran WJ, Whittington R, Peters AJ, Fanning J. Vaginal recurrences of endometrial carcinoma: the prognostic value of staging by a primary vaginal carcinoma system. Int J Radiat Oncol Biol Phys. 1988;15:803–8.

    Article  PubMed  Google Scholar 

  52. Lin LL, Grigsby PW, Powell MA, Mutch DG. Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer. Int J Radiat Oncol Biol Phys. 2005;63:500–4.

    Article  PubMed  Google Scholar 

  53. Jereczek-Fossa B, Badzio A, Jassem J. Recurrent endometrial cancer after surgery alone: results of salvage radiotherapy. Int J Radiat Oncol Biol Phys. 2000;48:405–13.

    Article  CAS  PubMed  Google Scholar 

  54. Morgan J, Reddy S, Sarin P, et al. Isolated vaginal recurrences of endometrial carcinoma. Radiology. 1993;189:609–13.

    Article  PubMed  Google Scholar 

  55. Lee LJ, Damato A, Viswanathan AN. Clinical outcomes following 3D image-guided brachytherapy for vaginal recurrence of endometrial cancer. Gynecol Oncol. 2013;131:586–92.

    Article  PubMed  Google Scholar 

  56. Vargo JA, Kim H, Houser CJ, et al. Definitive salvage for vaginal recurrence of endometrial cancer: the impact of modern intensity-modulated-radiotherapy with image-based HDR brachytherapy and the interplay of the PORTEC 1 risk stratification. Radiother Oncol. 2014;113(1):126–31.

    Article  PubMed  Google Scholar 

  57. Howlander N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975–2011, National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/csr/1975_2011/, Based on November 2013 SEER data submission, posted to the SEER website, April 2014. Accessed 24 March 2015.

  58. Taghian A, Pernot M, Hoffstetter S, et al. Radiation therapy alone for medically inoperable patients with adenocarcinoma of the endometrium. Int J Radiat Oncol Biol Phys. 1998;15:1135–40.

    Article  Google Scholar 

  59. Fishman DA, Roberts KB, Chambers JT, et al. Radiation therapy as exclusive treatment for medically inoperable patients with stage I and II endometrioid carcinoma with endometrium. Gynecol Oncol. 1996;61:189–96.

    Article  CAS  PubMed  Google Scholar 

  60. Knocke TH, Kucera H, Weidinger B, et al. Primary treatment of endometrial carcinoma with hig-dose-rate brachytherapy: results of 12 years of experience with 280 patients. Int J Radiat Oncol Biol Phys. 1997;37:359–65.

    Article  CAS  PubMed  Google Scholar 

  61. Kucera H, Knocke TH, Kucera E, et al. Treatment of endometrial carcinoma with high-dose-rate brachytherapy alone in medically inoperable stage I patients. Acta Obstet Gynecol Scand. 1998;77:1008–12.

    Article  CAS  PubMed  Google Scholar 

  62. Nguyen TV, Petereit DG. High-dose-rate brachytherapy for medically inoperable stage I endometrial cancer. Gynecol Oncol. 1998;71:196–203.

    Article  CAS  PubMed  Google Scholar 

  63. Sorbe B, Frankendal B, Risberg B. Intracavitary irradiation of endometrial carcinoma stage I by a high dose-rate afterloading technique. Gynecol Oncol. 1989;33:135–45.

    Article  CAS  PubMed  Google Scholar 

  64. Weitmann HD, Potter R, Waldhausl C, et al. Pilot study in the treatment of endometrial carcinoma with 3D image-based high-dose-rate brachytherapy using modified Heyman packing: clinical experience and dose-volume histogram analysis. Int J Radiat Oncol Biol Phys. 2005;62:468–78.

    Article  PubMed  Google Scholar 

  65. Wegner RE, Beriwal S, Heron DE, et al. Definitive radiation therapy for endometrial cancer in medically inoperable elderly patients. Brachytherapy. 2010;9(3):260–5.

    Article  PubMed  Google Scholar 

  66. Gill BS, Kim H, Houser C, et al. Image-based three-dimensional conformal brachytherapy for medically inoperable endometrial carcinoma. Brachytherapy. 2014;13:542–7.

    Article  PubMed  Google Scholar 

  67. Schwartz JK, Beriwal S, Esthappan J, et al. Consensus statement for brachytherapy for the treatment of medically inoperable endometrial cancer. Brachytherapy. 2015;14(5):587–99.

    Article  Google Scholar 

  68. Acharya S, Perkins SM, DeWees T, et al. Brachytherapy is associated with improved survival in inoperable stage I endometrial adenocarcinoma: a population-based analysis. Int J Radiat Oncol Biol Phys. 2015;93(3):649–57.

    Article  PubMed  Google Scholar 

  69. Gill BS, Chapman BV, Hansen KJ, et al. Primary radiotherapy for nonsurgically managed stage I endometrial cancer: utilization and impact of brachytherapy. Brachytherapy. 2015;14(3):373–9.

    Article  PubMed  Google Scholar 

  70. Vargo JA, Boisen MM, Comerci JT, et al. Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria. Gynecol Oncol. 2014;135(2):190–5.

    Article  PubMed  Google Scholar 

  71. Reisinger SA, Staros EB, Feld R, et al. Preoperative radiation therapy in clinical stage II endometrial carcinoma. Gynecol Oncol. 1992;45:174–8.

    Article  CAS  PubMed  Google Scholar 

  72. Maruyama Y, Yoneda J, Coffey C, et al. Tandem vaginal cylinder applicator for radiation therapy of uterine adenocarcinoma. Radiother Oncol. 1992;25:140–1.

    Article  CAS  PubMed  Google Scholar 

  73. Higgins RV, van Nagell JR, Horn EJ, et al. Preoperative radiation therapy followed by extrafascial hysterectomy in patients with stage II endometrial carcinoma. Cancer. 1991;68:1261–4.

    Article  CAS  PubMed  Google Scholar 

  74. Komaki R, Cox JD, Hartz A, et al. Influence of preoperative irradiation on failures of endometrial carcinoma with high risk of lymph node metastases. Am J Clin Oncol. 1984;7:661–8.

    Article  CAS  PubMed  Google Scholar 

  75. Pai HH, Souhami L, Clark BG, Roman T. Isolated vaginal recurrences in endometrial carcinoma: treatment results using high-dose-rate intracavitary brachytherapy and external beam radiotherapy. Gynecol Oncol. 1997;66(2):300–7.

    Article  CAS  PubMed  Google Scholar 

  76. Petignat P, Jolicoeur M, Alobaid A, Drouin P, et al. Salvage treatment with high-dose-rate brachytherapy for isolated vaginal endometrial cancer recurrence. Gynecol Oncol. 2006;101(3):445.

    Article  PubMed  Google Scholar 

  77. Lewin SN, Herzog TJ, Barrena Medel NI, et al. Comparative performance of the 2009 International Federation of gynecology and obstetrics’ staging system for uterine corpus cancer. Obstet Gynecol. 2010;116(5):1141–9.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Magee-Womens Hospital, 300 Halket Street, Pittsburgh, PA, 15213, USA

    Beant S. Gill, David Minkoff & Sushil Beriwal

Authors
  1. Beant S. Gill
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Minkoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sushil Beriwal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sushil Beriwal.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gill, B.S., Minkoff, D. & Beriwal, S. Current Concepts in Radiation Therapy for Early-Stage Endometrial Cancer. Indian J Gynecol Oncolog 13, 17 (2015). https://doi.org/10.1007/s40944-015-0023-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40944-015-0023-3

Keywords

Search

Navigation