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A proposal for a new classification of “unfavorable risk criteria” in patients with stage I endometrial cancer
  1. Richard Li1,
  2. Ashwin Shinde1,
  3. Ernest Han2,
  4. Stephen Lee2,
  5. Sushil Beriwal3,
  6. Matthew Harkenrider4,
  7. Mitchell Kamrava5,
  8. Yi-Jen Chen1 and
  9. Scott Glaser1
  1. 1 Radiation Oncology, City of Hope Medical Center, Duarte, California, USA
  2. 2 Gynecologic Oncology, City of Hope Medical Center, Duarte, California, USA
  3. 3 Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
  4. 4 Radiation Oncology, Stritch School of Medicine; Loyola University Chicago, Maywood, Illinois, USA
  5. 5 Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California, USA
  1. Correspondence to Dr Scott Glaser, Radiation Oncology, City of Hope Medical Center, Duarte, CA 91010, USA; sglaser{at}


Background Randomized trials describe differing sets of high–intermediate risk criteria.

Objective To use the National Cancer Database to compare the impact of radiation therapy in patients with stage I endometrial cancer meeting different criteria, and define a classification of “unfavorable risk.”

Methods Patients with stage I endometrial cancer between January 2010 and December 2014 were identified in the National Cancer Database and stratified into two cohorts: (1) patients meeting Gynecologic Oncology Group (GOG)-99 criteria only for high–intermediate risk, but not Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 criteria and (2) those meeting PORTEC-1 criteria only. High-risk stage I patients with both FIGO stage IB (under FIGO 2009 staging) and grade 3 disease were excluded. In each cohort, propensity score-matched survival analyses were performed. Based on these analyses, we propose a new classification of unfavorable risk. We then analyzed the association of adjuvant radiation with survival, stratified by this classification.

Results We identified 117,272 patients with stage I endometrial cancer. Of these, 11,207 patients met GOG-99 criteria only and 5,920 patients met PORTEC-1 criteria only. After propensity score matching, adjuvant radiation therapy improved survival (HR=0.73; 95% CI 0.60 to 0.89; p=0.002) in the GOG-99 only cohort. However, there was no benefit of adjuvant radiation (HR=0.89; 95% CI 0.69 to 1.14; p=0.355) in the PORTEC-1 only cohort. We, therefore, defined unfavorable risk stage I endometrial cancer as two or more of the following risk factors: lymphovascular invasion, age ≥70, grade 2–3 disease, and FIGO stage IB. Adjuvant radiation improved survival in stage I patients with adverse risk factors (HR=0.74; 95% CI 0.68 to 0.80; p<0.001), but not in other stage I patients (HR=1.02; 95% CI 0.91 to 1.15; p=0.710; p interaction <0.001).

Conclusion Our study showed that adjuvant radiation was associated with an overall survival benefit in patients meeting GOG-99 criteria only; however, no survival benefit was seen in patients meeting PORTEC-1 criteria only. We propose a definition of unfavorable risk stage I endometrial cancer: ≥2 risk factors from among lymphovascular invasion, age ≥70, grade 2–3 disease, and FIGO stage IB disease.

  • endometrial neoplasms
  • radiation oncology
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  • Contributors RL and SG conceived the original concept of the manuscript and designed the initial analysis. RL, SG, AS, EH, SL, SB, MH, MK, and Y-JC contributed to the analysis and writing of the paper.

  • 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 None declared.

  • Patient consent for publication Not required.

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

  • Data sharing statement Data are available upon reasonable request.

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