Lymphadenectomy in women with endometrial cancer: aspiration and reality from a radiation oncologist’s point of view

Foerster et al. Radiation Oncology (2015) 10:147 DOI 10.1186/s13014-015-0460-2 RESEARCH Open Access Lymphadenectomy in women with endometrial cancer: aspiration and reality from a radiation oncologist’s point of view Robert Foerster*, Robert Kluck, Nathalie Arians, Stefan Rieken, Harald Rief, Sebastian Adeberg, Tilman Bostel, Ingmar Schlampp, Juergen Debus and Katja Lindel Abstract Background: To investigate the meaning of lymphadenectomy (LNE) in women with endometrial cancer (EC) for clinical outcome and secondly to determine the impact of the method of adjuvant radiotherapy (RT) on survival as well as to define prognostic factors. Methods: 322 patients (pts) underwent adjuvant RT for endometrioid EC at our department from 2004 until 2012 and were included in this retrospective study. Chi-square test, LogRank test and Cox regression were used for statistical analyses. Results: Median age at diagnosis: 66 years. FIGO stages: FIGO I 69.4 %, FIGO II 15.3 %, FIGO III 14.5 %, FIGO IV 0.9 %. Surgical staging: 30.6 % pelvic/paraaortic LNE, 45 % sole pelvic LNE, 8.8 % sampling of suspicious lymph nodes, 15.6 % no LNE. Adjuvant chemotherapy (ChT): 3.2 %. Sole intravaginal brachytherapy (IVB): 60.2 %. IVB + external beam radiotherapy (EBRT): 39.8 %. 5-year local recurrence free survival (LRFS): 90.6 %, distant metastases free survival (DMFS): 89.8 %, overall survival (OS):79.3 %. In multivariate analysis age (p = .007), pT stage (p = .029), lymph node status (p = .003), grading (p = .011) and lymphovascular space invasion (LVSI; p = .008) remained as independent prognostic factors for OS. Resection status (p = .01) and LVSI (p = .014) were independent prognostic factors for LRFS and LVSI (p = .008) was the only independent prognostic factor for DMFS. There was no statistically significant survival benefit from LNE in LRFS (p = .561), DMFS (p = .981) or OS (p = .791). 5-year LRFS in stage I and II: 96.0 and 82.9 % after sole IVB, 90.8 and 81.6 % after combined IVB/EBRT (p = .105; p = .970). 5-year OS rates for stage I and II: 86.5 and 71.3 % after sole IVB, 84.2 % and 69.2 % after combined IVB/EBRT (p = .153; p = .619). Conclusion: Comprehensive surgical staging is rarely performed and may be omitted in women with endometrioid EC in stages I-II. Sole IVB delivers equally good local control as combined IVB/EBRT in pts with FIGO stage I and II disease. LVSI deserves more attention as a prognostic factor and these pts may require a combined local and systemic therapy. Keywords: Adjuvant radiotherapy, Endometrial cancer, Lymphadenectomy, Prognostic factors, Survival * Correspondence: Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany © 2015 Foerster et al.. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Foerster et al. Radiation Oncology (2015) 10:147 Background Endometrial cancer (EC) is the most common gynecologic malignancy. While therapy guidelines are widely established and the prognosis is generally favorable, optimal treatment remains controversial. In particular the conductance of systematic lymphadenectomy (LNE) and the role of external beam radiotherapy (EBRT) in early stages have been actively disputed, since both therapy modalities are known to cause substantial morbidity. Current guidelines recommend systematic pelvic and paraaortic LNE with investigation of at least 15 pelvic and 10 paraaortic lymph nodes from FIGO IB onward [1, 2]. However, clinical practice differs among surgical centers and many patients are spared LNE or only undergo sampling of suspicious pelvic lymph nodes commonly omitting paraaortic lymph nodes. For radiation oncologists it can be challenging to recommend the appropriate adjuvant therapy for these patients (pts), especially when they present with additional risk factors, such as grade-3- histology or lymphovascular space invasion (LVSI). We therefore designed this retrospective analysis to elucidate the clinical outcome in the pts treated with adjuvant radiotherapy (RT) at our department and further to investigate the role of LNE and known prognostic factors. Methods Between 2004 and 2012 we performed adjuvant RT in 322 women with endometrioid EC at our department. All pts were included in this retrospective study, which was approved by the ethics committee of the University of Heidelberg. Due to its retrospective and blinded design consent was not required. By revision of the electronic patient charts we collected detailed information on stage, grading, resection status, LVSI, primary surgical therapy, adjuvant RT and additional adjuvant chemotherapy (ChT). FIGO 2009 classification was used for staging and patients were reclassified if necessary. Survival analysis was done for local recurrence free survival (LRFS), distant metastases free survival (DMFS) and overall survival (OS). LRFS was considered to be the time between first diagnosis and first recurrence within the irradiation field. DMFS was calculated as the time from first diagnosis until distant relapse. OS was calculated from date of first diagnosis until death from any cause. Survival was plotted according to Kaplan and Meier. The Log-rank test was used for univariate analysis and Cox proportional hazard model was used for multivariate analysis. The Chi-square test was used to illustrate heterogeneity among treatment groups. A p-value ≤ .05 was considered statistically significant. Statistical analysis was performed with SPSS 22.0 for Windows. Page 2 of 7 Results Patients’ and tumor characteristics Pts were first diagnosed with EC at a median age of 66 years (range: 36–92). FIGO stages were distributed as follows: stage I 69.4 %, stage II 15.3 %, stage III 14.5 %, stage IV 0.9 %. Positive lymph nodes (N1) were found in 9.7 %, 24.2 % had an undifferentiated tumor grading (G3) and 16.5 % showed LVSI. Resection was incomplete (R2) in 0.3 %, microscopically positive resection margins (R1) were found in 2.2 % and resection status was indeterminable (Rx) in 5.0 % (Table 1). Primary surgical therapy consisted of hysterectomy and bilateral salpingo-oophorectomy in all patients. Pelvic and paraaortic LNE was conducted in 98 pts (30.6 %), 144 (45.0 %) received sole pelvic LNE, 28 (8.8 %) only underwent sampling of suspicious lymph nodes and in 50 (15.6 %) LNE was omitted. RT consisted of EBRT in 1.8 − 2.0 Gy fractions to a cumulative dose of 40.0 − 54.0 Gy and / or high dose rate (HDR) intravaginal brachytherapy (IVB) in 5.0 − 5.5 Gy fractions to a cumulative dose of 10.0 − 22.0 Gy. One hundred twenty eight ( (...truncated)