|Year : 2015 | Volume
| Issue : 4 | Page : 682-684
Tumor recurrence and tumor-related mortality in endometrial cancer: Analysis in 276 patients
A Tejerizo-Garcia, C Álvarez-Conejo, L Muñoz-Hernando, C Guillñn-Gámez, JM Seoane-Ruiz, C Pñrez-Sagaseta, JS Jimñnez-López
Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Madrid, Spain
|Date of Web Publication||10-Mar-2016|
J S Jimñnez-López
Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Madrid
Source of Support: None, Conflict of Interest: None
BACKGROUND: In this manuscript, we assessed tumor recurrence and tumor-related mortality in a clinical series of endometrial cancer patients. MATERIALS AND METHODS: A retrospective evaluation of 276 patients (mean age 64 years) with histologically confirmed endometrial cancer treated at a single hospital in Madrid (Spain) was conducted. The median follow-up was estimated using the inverse Kaplan–Meier method. RESULTS: Salient findings were endometrioid carcinoma (84.8% of cases), grade G1 (48.9%) and stages IB (35.1%) and IC (23.2%). Myometrial infiltration >50% was documented in 31.2% of cases and lymphovascular space invasion in 11.9%. After surgery, 52.5% of patients were classified into the low risk group, 21.4% into the intermediate risk group and 26.1% into the high risk group. Tumor recurrence occurred in 14.5% of patients, with an estimated median follow-up of 45 months (95% confidence interval (CI): 41.2–48.8), locoregional recurrence in 42.5% and distant recurrences in 57.5%. Furthermore, 40% of tumor recurrences developed during the first year after primary treatment and 90% over the first 3 years of follow-up. The tumor-related mortality rate was 15.9%. The estimated median follow-up was 46 months (95% CI: 43.0–49.0). Furthermore, 5.07% of death because of tumor developed during the first year after primary treatment and 13.77% over the first 3 years of follow-up. CONCLUSION: The rates of tumor-related death and tumor recurrence in endometrial cancer patients are low, with the highest percentages occurring within 3 years of primary treatment. Most of the recurrences occur outside the pelvis.
Keywords: Endometrial cancer, tumor recurrence, tumor-related death
|How to cite this article:|
Tejerizo-Garcia A, Álvarez-Conejo C, Muñoz-Hernando L, Guillñn-Gámez C, Seoane-Ruiz J M, Pñrez-Sagaseta C, Jimñnez-López J S. Tumor recurrence and tumor-related mortality in endometrial cancer: Analysis in 276 patients. Indian J Cancer 2015;52:682-4
|How to cite this URL:|
Tejerizo-Garcia A, Álvarez-Conejo C, Muñoz-Hernando L, Guillñn-Gámez C, Seoane-Ruiz J M, Pñrez-Sagaseta C, Jimñnez-López J S. Tumor recurrence and tumor-related mortality in endometrial cancer: Analysis in 276 patients. Indian J Cancer [serial online] 2015 [cited 2020 Jul 16];52:682-4. Available from: http://www.indianjcancer.com/text.asp?2015/52/4/682/178425
| » Introduction|| |
Carcinoma of the endometrium remains the most common gynecologic malignancy, with an incidence of 5.12/100,000 and mortality of 1.21/100,000 in Spain in 2012. The objective of this study was to assess timing and site of recurrences and endometrial cancer-related mortality in a clinical series of 276 patients diagnosed and treated for endometrial cancer in a single institution.
| » Materials and Methods|| |
A retrospective single center study was performed of all consecutive patients treated for histologically confirmed endometrial cancer between January 2001 and December 2007. All patients were fully informed of diagnostic workup studies and surgical procedures and gave informed consent. Approval of the Ethics Committee of the Hospital was obtained for retrospective chart review.
Standard surgical treatment included peritoneal cytology sampling, extrafascial total hysterectomy and bilateral salpingo-oophorectomy combined with selective pelvic/para-aortic node dissection according to the risk for Recurrence. In the presence of histological types with poor prognosis (serous-papillary, clear cells or undifferentiated tumors) omentectomy was also performed.
Clinical stages and pathological grading were reviewed according to the International Federation of Gynecology and Obstetrics (FIGO) classification (1988). Tumor grade was evaluated including architectural and nuclear grade.
Adjuvant treatment was discussed together with radiotherapists, pathologists and medical oncologists in multidisciplinary team meetings. External beam radiotherapy was indicated in stages IB or IC G3, IIA G3 and >IIB, in combination with endocavitary radiotherapy in stages ≥IB G3. Adjuvant chemotherapy was added to high risk patients.
The analysis of disease-free survival was performed with 272 patients: Three patients are not included in the analysis of recurrence-free survival because it never healed, and therefore are not at risk of relapse.
The statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS Inc., Chicago IL) version 15.0. Three patients in which curative procedures could not be performed were excluded from the analysis of tumor recurrence. The median follow-up was estimated using the inverse Kaplan–Meier method.
| » Results|| |
After excluding patients with inoperable tumors or incomplete follow-up the study population consisted of 276 patients, with a mean (standard deviation) age of 64 (11) years (range 29–91 years) and a mean body mass index (BMI) of 30.8 (6.1) kg/m 2 (range 17.4–51.6 kg/m 2). The BMI was ≥30 kg/m 2 in 31 patients. 87% (n = 241) of women were menopausal. History of breast cancer was recorded in 30 patients (treatment with tamoxifen in 25) and of colorectal cancer in four. Six (2.2%) patients had received hormonal replacement therapy and two (0.7%) were treated with patients oral contraceptives.
Briefly, surgical treatment included standard total hysterectomy and bilateral salpingo-oophorectomy in 274 patients (laparotomy, n = 82; laparoscopy, n = 192), radical hysterectomy in two. Pelvic and/or para-aortic lymphadenectomy was performed in 150 patients, with negative histological findings in 137 (91.3%) and positive in 13 (8.7%). Lymphadenectomy was more common with laparoscopy than with laparotomy (55.2% vs. 51.2%). About 50% of patients received adjuvant radiotherapy and 3.2% platine-based chemotherapy.
[Table 1] shows surgical stage, grade and histological condition of endometrial cancers. The most frequent characteristics were endometrioid carcinoma (84.8% of cases), grade G1 (48.9%) and stages IB (35.1%) and IC (23.2%). Myometrial infiltration <50% was documented in 39.1% of cases and >50% in 31.2%. Lymphovascular space invasion was found in 11.9% of cases. Peritoneal cytology was negative in 91.3% of cases. After surgery, 52.5% of patients were classified into the low risk group, 21.4% into the intermediate risk group and 26.1% into the high risk group.
Tumor recurrence was documented in 14.5% (40/273) of patients, with an estimated median follow-up using the inverse Kaplan–Meier method of 45 months (95% confidence interval (CI): 41.2–48.8). Locoregional recurrences occurred in 17 (42.5%) patients and distant recurrences in the remaining 23 (57.5%). As shown in [Table 2], the most common site of recurrence was the vaginal vault (30%) followed by the pelvis (12.5%) and the para-aortic/retroperitoneal space (7.5%). Furthermore, 40% of tumor recurrences developed during the first year after primary treatment and 90% over the first 3 years of follow-up.
|Table 2: Site and time of appearance of tumor recurrence in 273 endometrial cancer patients|
Click here to view
The tumor-related mortality rate was 15.9% (n = 44). The estimated median follow-up using the inverse Kaplan–Meier method was 46 months (95% CI: 43.0–49.0).
Furthermore, 5.07% of death because of tumor developed during the first year after primary treatment and 13.77% over the first 3 years of follow-up.
The disease-free 5-year survival was 82.3% and the overall 5-year survival 81% [Figure 1].
|Figure 1: Disease-free survival (upper panel) and overall survival (lower panel) in the study population|
Click here to view
Patients with recurrence and patients who died due to endometrial cancer showed similar characteristics, as shown in [Table 1]. In groups of tumor recurrence and tumor-related death, the most common findings were: Endometrioid tumors (60% and 69% of cases, respectively), G2 tumor grade (37.5% and 31.8%), FIGO stages IC (32.5% and 25%), IIB (10% and 14%), IIIA (20% and 15.9%), IIIC (15% and 15.9%) and IV (2.5% and 2.3%), outer half myometrial invasion (>50%) (67.5% and 54.5%), frank lymphovascular invasion (35% and 27.3%), and use of laparoscopic surgery (60% and 56.8%). In patients with tumor recurrence, lymphadenectomy was performed in 26 (65%) patients, with positive lymph nodes in seven cases. Tumor remnants >1 cm after surgery were documented in three (7.5%) patients. Adjuvant chemotherapy and radiation therapy were administered to 4 and 26 patients, respectively. In the group of patients who died, lymphadenectomy was performed in 24 (54.5%) patients, in 12 of which positive lymph nodes were found. Tumor remnants >1 cm after surgery were documented in five (11.4%) patients. Adjuvant chemotherapy and radiation therapy were administered to 5 and 30 patients, respectively.
In the multivariate Cox regression model [Table 3], predictors of tumor recurrence included advanced FIGO stage (hazard ratio [HR] =4.90, 95% CI 2.57–9.36, P < 0.001) and grades G2 (HR = 4.79, 95% CI: 1.73–13.27, P = 0.003) and G3 (HR = 7.56, 95% CI: 2.75–20.73, P < 0.001). The same variables were also associated with a significantly higher risk of tumor-related mortality, with a HR of 4.90 (95% CI: 2.57–9.36) (P < 0.001) for advanced FIGO stage, HR of 3.54 (95% CI: 1.35–931), (P = 0.01) for G2 and HR of 6.76 (95% CI: 2.65–17.13) (P < 0.001) for G3.
|Table 3: Results of multivariate Cox proportional hazards analysis for FIGO stage and tumor grade|
Click here to view
| » Discussion|| |
In this study, the rate of tumor recurrence after definitive primary treatment of endometrial cancer was 14.5%. This percentage is consistent with rates previously reported in other studies ranging between 10% and 18%. The natural history of corpus cancers includes extrauterine spread through hematogenous dissemination, lymphatic embolization, contiguous extension, or peritoneal seeding, or a combination of these. In our study, tumor recurrences were grouped into vaginal, pelvic, para-aortic, distant (including extrapelvic localizations other than in the para-aortic space), and multifocal, which may be simplified into local recurrences (42.5%), distant recurrences (47.5%), and multifocal (10%). These findings are very similar to the experience of other authors, such in the series of Sohaib et al. with 34.4% of local recurrences, 46.9% of distant recurrences and 18.8% in both sites, or in the systematic review of Fung-Fee-Fung et al. with 61% of distant metastases including multifocal relapses and 39% of local recurrences. Therefore, data of our study confirm a trend reported by the majority of studies that distant recurrences are more common than local recurrences after primary treatment of endometrial cancer. This fact is probably due to pelvic adjuvant radiotherapy after surgery.
An interesting finding is the low rate of para-aortic recurrence in our population (7.5% of cases) as compared with other studies, such as that or Murphy et al. with 37.5% or Kyo et al. with 25%. These differences may be explained by the favorable tumor characteristics of most patients included in the study together with the use of adjuvant radiation therapy in those at higher risk of recurrence in the para-aortic area.
On the other hand, the analysis of tumor recurrences in relation to the time elapsed from primary therapy for endometrial cancer shows that in 40% of cases the recurrence was detected during the first year and in 90% of cases over the first 3 years of follow-up. These data are in concordance with percentages reported by others.
According to the 26th annual report on the results of treatment in gynecological cancer, approximately 22% of patients treated for endometrial cancer died within 5 years. In a two large studies that investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer, the overall mortality rate was 13.6% (after a median follow-up of 37 months) in the Assam Science Technology and Environment Council surgical trial  and 10.3% (after a median follow-up of 49 months) in the randomized clinical trial reported by Benedetti Panici et al. The percentage of tumor-related deaths of 15.9% found in our study is consistent with the aforementioned reports, although the smaller study sample may account for a somewhat higher percentage in the present series.
In summary, the rates of tumor-related death and tumor recurrence in endometrial cancer patients are low, with the highest percentages occurring within 3 years of primary treatment. Recurrences are often found outside the pelvis because of the higher therapeutic effort concentrated on this focus. It is probable that systemic chemotherapy in endometrial cancer patients with high risk of recurrence may help to reduce the percentage of distant metastasis.
| » Acknowledgment|| |
We thank Marta Pulido, MD, for editing the manuscript and editorial assistance.
| » References|| |
Wright JD, Barrena Medel NI, Sehouli J, Fujiwara K, Herzog TJ. Contemporary management of endometrial cancer. Lancet 2012;379:1352-60.
Sohaib SA, Houghton SL, Meroni R, Rockall AG, Blake P, Reznek RH. Recurrent endometrial cancer: Patterns of recurrent disease and assessment of prognosis. Clin Radiol 2007;62:28-34.
Fung-Kee-Fung M, Dodge J, Elit L, Lukka H, Chambers A, Oliver T, et al
. Follow-up after primary therapy for endometrial cancer: A systematic review. Gynecol Oncol 2006;101:520-9.
Murphy KT, Rotmensch J, Yamada SD, Mundt AJ. Outcome and patterns of failure in pathologic stages I-IV clear-cell carcinoma of the endometrium: Implications for adjuvant radiation therapy. Int J Radiat Oncol Biol Phys 2003;55:1272-6.
Kyo S, Hashimoto M, Maida Y, Mizumoto Y, Nakamura M, Takakura M, et al
. Analysis of outcome of Stage I-III endometrial cancer treated with systematic operation omitting paraaortic lymphadenectomy. Eur J Gynaecol Oncol 2007;28:170-3.
Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, 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 Suppl 1:S105-43.
ASTEC study group, Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): A randomised study. Lancet 2009;373:125-36.
Benedetti Panici P, Basile S, Maneschi F, Alberto Lissoni A, Signorelli M, Scambia G, et al
. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: Randomized clinical trial. J Natl Cancer Inst 2008;100:1707-16.
[Table 1], [Table 2], [Table 3]
|This article has been cited by|
||A Proposal for a Classification for Recurrent Endometrial Cancer: Analysis of a French Multicenter Database From the FRANCOGYN Study Group
| ||Alexandre Bricou,Sofiane Bendifallah,Mathilde Daix-Moreux,Lobna Ouldamer,Vincent Lavoue,Amélie Benbara,Cyrille Huchon,Geoffroy Canlorbe,Emilie Raimond,Charles Coutant,Olivier Graesslin,Pierre Collinet,Xavier Carcopino,Cyril Touboul,Emile Daraï,Lionel Carbillon,Marcos Ballester |
| ||International Journal of Gynecologic Cancer. 2018; 28(7): 1278 |
|[Pubmed] | [DOI]|
||Vaginal implantation metastasis of endometrial carcinoma: A case report
| ||YUELING WANG,JIANG DU,SHULAN LV,YANXIA SUI,XUE XUE,CHAO SUN,JUNKAI ZOU,QUNYING MA,GUOXING FU,QING SONG,QILING LI |
| ||Oncology Letters. 2016; 12(1): 513 |
|[Pubmed] | [DOI]|