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Adjuvant treatment improves overall survival in women with high-intermediate risk early-stage endometrial cancer with lymphovascular space invasion
  1. Ji Son1,
  2. Laura M Chambers2,
  3. Caitlin Carr1,
  4. Chad M Michener2,
  5. Meng Yao3,
  6. Anna Beavis4,
  7. Ting-Tai Yen4,
  8. Rebecca L Stone4,
  9. Stephanie L Wethington4,
  10. Amanda N Fader4,
  11. Wesley C Burkett5,
  12. Debra L Richardson6,
  13. Allison S Staley7,
  14. Susie Ahn8,
  15. Paola A Gehrig7,
  16. Diogo Torres9,
  17. Sean C Dowdy9,
  18. Mackenzie W Sullivan10,
  19. Susan C Modesitt11,
  20. Catherine Watson12,
  21. Ashley Veade13,
  22. Jessie Ehrisman13,
  23. Laura Havrilesky12,
  24. Angeles Alvarez Secord12,
  25. Amy Loreen14,
  26. Kaitlyn Griffin14,
  27. Amanda Jackson15,
  28. Akila Viswanathan16 and
  29. Stephanie Ricci2
  1. 1Department of Obstetrics and Gynecology, Women's Health Institute, Cleveland Clinic, Cleveland, Ohio, USA
  2. 2Division of Gynecologic Oncology, Women's Health Institute, Cleveland Clinic, Cleveland, Ohio, USA
  3. 3Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA
  4. 4The Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  5. 5Department of Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
  6. 6Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
  7. 7Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  8. 8Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  9. 9Division of Gynecologic Surgery, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA
  10. 10Department of Obstetrics and Gynecology, University of Virginia Health System, Charlottesville, Virginia, USA
  11. 11Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Virginia Health System, Charlottesville, Virginia, USA
  12. 12Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA
  13. 13Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA
  14. 14Department of Obstetrics and Gynecology, University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA
  15. 15Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA
  16. 16Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  1. Correspondence to Dr Stephanie Ricci; riccis{at}ccf.org

Abstract

Background Adjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial.

Objective To determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes.

Methods A multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis.

Results 405 patients were included with the median age of 67 years (range 27–92, IQR 59–73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, p<0.001). After adjusting for stage, grade 2/3, and age, improved progression-free survival and overall survival were observed for the following adjuvant subgroups compared with observation: external beam radiation (overall survival HR 0.47, p=0.047, progression-free survival not significant), vaginal brachytherapy (overall survival HR 0.35, p<0.001; progression-free survival HR 0.42, p=0.003), and brachytherapy + chemotherapy (overall survival HR 0.30 p=0.002; progression-free survival HR 0.35, p=0.006). Compared with vaginal brachytherapy alone, external beam radiation or the addition of chemotherapy did not further improve progression-free survival (p=0.80, p=0.65, respectively) or overall survival (p=0.47, p=0.74, respectively).

Conclusion Adjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone.

  • endometrium
  • uterine cancer
  • pathology
  • lymphatic vessels
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Footnotes

  • Twitter @laurajmoulton, @amandanfader, @wcburkett

  • Contributors Conception, data analysis and interpretation, manuscript drafting: JS, LMC, SR. Additional interpretation and analytical edits: CC, CMM, MY, PAG, DT. Statistical support: MY. Conception and management of the original full database: ALB, T-TY, ANF. Data collection, management: JS, LMC, CC, ALB, T-TY, RLS, SLW, ANF, WCB, DLR, AS-S, SA, PAG, DT, SCD, MWS, SCM, CW, AVe, JE, LH, AAS, AL, KG, AJ, AVi. All authors critically revised the manuscript and approved the manuscript in its final version prior to submission.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests All authors reported their potential conflict of interest and there were none directly relating to this study.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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