Cancer Res Treat.  2016 Jul;48(3):1074-1083. 10.4143/crt.2015.356.

Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma

• Yoon MS
• Huh SJ
• Kim HJ
• Kim YS
• Kim YB
• Kim JY
• Lee JH
• Kim HJ
• Cha J
• Kim JH
• Kim J
• Yoon WS
• Choi JH
• Chun M
• Choi Y
• Lee KK
• Kim M
• Jeong JU
• Chang SK
• Park W

• KMID: 2344081
• DOI: http://doi.org/10.4143/crt.2015.356

Abstract

PURPOSE
We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group.
MATERIALS AND METHODS
A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed.
RESULTS
Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively).
CONCLUSION
We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT.

Keyword

Endometrial neoplasms; Adjuvant radiotherapy; Adjuvant chemoradiotherapy

MeSH Terms

Adenocarcinoma*
Carcinoma, Endometrioid
Chemoradiotherapy
Chemoradiotherapy, Adjuvant
Disease-Free Survival
Endometrial Neoplasms
Female
Humans
Multivariate Analysis
Neoplasm Metastasis
Radiotherapy
Radiotherapy, Adjuvant
Recurrence
Retrospective Studies
Risk Factors

Figure

• 

  Fig. 1. Kaplan-Meier survival curve of disease-free survival (A) and overall survival (B) according to the low-risk group with no or one risk factor and the high-risk group with two or three risk factors (risk factor: age ≥ 60 or ≥ G2 or lymphovascular space invasion).

• 

  Fig. 2. Subgroup analysis according to treatment modality. Disease-free survival and overall survival in the radiotherapy alone group (A) and the chemoradiotherapy group (B). The low-risk group with no or one risk factor and the high-risk group with two or three risk factors (risk factor: age ≥ 60 years or ≥ G2 or lymphovascular space invasion).

Reference

References

1. Jobsen JJ, ten Cate LN, Lybeert ML, van der Steen-Banasik EM, Scholten A, van der Palen J, et al. The number of metastatic sites for stage IIIA endometrial carcinoma, endometrioid cell type, is a strong negative prognostic factor. Gynecol Oncol. 2010; 117:32–6.

2. Kato T, Watari H, Endo D, Mitamura T, Odagiri T, Konno Y, et al. New revised FIGO 2008 staging system for endometrial cancer produces better discrimination in survival compared with the 1988 staging system. J Surg Oncol. 2012; 106:938–41.

3. Connell PP, Rotmensch J, Waggoner S, Mundt AJ. The significance of adnexal involvement in endometrial carcinoma. Gynecol Oncol. 1999; 74:74–9.

4. Denschlag D, Tan L, Patel S, Kerim-Dikeni A, Souhami L, Gilbert L. Stage III endometrial cancer: preoperative predictability, prognostic factors, and treatment outcome. Am J Obstet Gynecol. 2007; 196:546.

5. Lum MM, Belnap TW, Frandsen J, Brown AP, Sause WT, Soisson AP, et al. Survival analysis of cancer patients with FIGO stage IIIA endometrial cancer. Am J Clin Oncol. 2015; 38:283–8.

6. Havrilesky LJ, Secord AA, O'Malley DM, Broadwater G, Bae-Jump V, Cohn DE, et al. Multicenter analysis of recurrence and survival in stage IIIA endometrial cancer. Gynecol Oncol. 2009; 114:279–83.

7. Lewin SN, Herzog TJ, Barrena Medel NI, Deutsch I, Burke WM, Sun X, et al. Comparative performance of the 2009 international Federation of gynecology and obstetrics' staging system for uterine corpus cancer. Obstet Gynecol. 2010; 116:1141–9.

8. Choi EC, Kim JH, Kim OB, Byun SJ, Park SG, Kwon SH. Postoperative radiotherapy for endometrial cancer. Radiat Oncol J. 2012; 30:108–16.

9. Schorge JO, Molpus KL, Goodman A, Nikrui N, Fuller AF Jr. The effect of postsurgical therapy on stage III endometrial carcinoma. Gynecol Oncol. 1996; 63:34–9.

10. Kuku S, Williams M, McCormack M. Adjuvant therapy in stage III endometrial cancer: treatment outcomes and survival: a single-institution retrospective study. Int J Gynecol Cancer. 2013; 23:1056–64.

11. Nakayama K, Nagai Y, Ishikawa M, Aoki Y, Miyazaki K. Concomitant postoperative radiation and chemotherapy following surgery was associated with improved overall survival in patients with FIGO stages III and IV endometrial cancer. Int J Clin Oncol. 2010; 15:440–6.

12. Hogberg T, Signorelli M, de Oliveira CF, Fossati R, Lissoni AA, Sorbe B, et al. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer: results from two randomised studies. Eur J Cancer. 2010; 46:2422–31.

13. Alvarez Secord A, Havrilesky LJ, Bae-Jump V, Chin J, Calingaert B, Bland A, et al. The role of multi-modality adjuvant chemotherapy and radiation in women with advanced stage endometrial cancer. Gynecol Oncol. 2007; 107:285–91.

14. Kuoppala T, Maenpaa J, Tomas E, Puistola U, Salmi T, Grenman S, et al. Surgically staged high-risk endometrial cancer: randomized study of adjuvant radiotherapy alone vs. sequential chemo-radiotherapy. Gynecol Oncol. 2008; 110:190–5.

15. Mariani A, Webb MJ, Keeney GL, Aletti G, Podratz KC. Assessment of prognostic factors in stage IIIA endometrial cancer. Gynecol Oncol. 2002; 86:38–44.

16. AlHilli MM, Mariani A, Bakkum-Gamez JN, Dowdy SC, Weaver AL, Peethambaram PP, et al. Risk-scoring models for individualized prediction of overall survival in low-grade and high-grade endometrial cancer. Gynecol Oncol. 2014; 133:485–93.

17. Marchetti C, Pisano C, Mangili G, Lorusso D, Panici PB, Silvestro G, et al. Use of adjuvant therapy in patients with FIGO stage III endometrial carcinoma: a multicenter retrospective study. Oncology. 2011; 81:104–12.

18. Jobsen JJ, Naudin Ten Cate L, Lybeert ML, Scholten A, van der Steen-Banasik EM, van der Palen J, et al. Outcome of endometrial cancer stage IIIA with adnexa or serosal involvement only. Obstet Gynecol Int. 2011; 2011:962518.

19. Lan C, Huang X, Huang Y, Xi S, Huang H, Feng Y, et al. The outcome and efficacy of adjuvant chemotherapy alone in patients with stage IIIA endometrial carcinoma with solitary adnexal involvement: a retrospective single-institution study. Gynecol Oncol. 2014; 135:446–50.

20. Ashman JB, Connell PP, Yamada D, Rotmensch J, Waggoner SE, Mundt AJ. Outcome of endometrial carcinoma patients with involvement of the uterine serosa. Gynecol Oncol. 2001; 82:338–43.