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CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2025; 85(07): 724-735
DOI: 10.1055/a-2589-0498
GebFra Science
Original Article

Minimally Invasive Surgery in Endometrial Cancer: Superior for Low-Risk and Comparable for High-Risk Cases in a 20-Year Cohort Study

Minimalinvasive Chirurgie zur Behandlung von Endometriumkarzinomen: 20-jährige Kohortenstudie zeigt bessere Ergebnisse bei Niedrigrisiko- und vergleichbare Ergebnisse für Hochrisiko-Patientinnen
Valentina Auletta
1   Department of Gynecology and Reproductive Medicine, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany (Ringgold ID: RIN39065)
,
Maya Ehab Hassan
1   Department of Gynecology and Reproductive Medicine, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany (Ringgold ID: RIN39065)
,
Angela Kather 
1   Department of Gynecology and Reproductive Medicine, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany (Ringgold ID: RIN39065)
2   Zentrum für Alternsforschung Jena – Aging Research Center Jena, Friedrich-Schiller-University Jena, Jena, Germany (Ringgold ID: RIN9378)
,
Nikolaus Gaßler
3   Section Pathology of the Institute of Forensic Medicine, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany (Ringgold ID: RIN39065)
,
Davit Bokhua
1   Department of Gynecology and Reproductive Medicine, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany (Ringgold ID: RIN39065)
,
Ingo B. Runnebaum
4   Department of gynecology and reproductive medicine, Jena University Hospital, Jena, Germany (Ringgold ID: RIN39065)
› Author Affiliations
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Abstract

Objective

Minimally invasive surgery (MIS) to treat endometrial cancer offers advantages over laparotomy, although concerns about its oncological safety for high-risk tumors and feasibility in patients with significant comorbidities remain. This study evaluates perioperative and long-term outcomes of MIS versus open surgery in a tertiary referral center cohort, using FIGO 2010 and 2023 classifications.

Methods

This is a retrospective analysis of perioperative outcomes, recurrence rates, and survival after endometrial cancer surgery (2000–2021) at an ESGO training center and tertiary referral center in Germany. 760 patients underwent hysterectomy, and adequate data for risk classification (without molecular diagnostics) was available for 330 of them.

Results

More than one third of the patients were aged 70 years or older and approximately half of the patients were obese. A high proportion presented with comorbidities such as hypertension or diabetes. MIS demonstrated favorable perioperative results in both low-risk and high-risk patients. Survival analysis showed a superior outcome with MIS for low-risk (5-year RFS rate: 79.8% vs. 59.2%, p = 0.035; OS rate: 83.8% vs. 58.0%, p = 0.010) and FIGO 2023 stage I disease (OS: p = 0.014). The oncological safety of MIS was equivalent to that of open surgery for high-risk tumors (5-year RFS rate: 60.5% vs. 54.3%, p = 0.506; OS rate: 67.5% vs. 58.3%, p = 0.416) and FIGO 2023 stages II (RFS, p = 0.453; OS, p = 0.378) and III (RFS, p = 0.419; OS, p = 0.850).

Conclusion

MIS was found to have superior outcomes for low-risk endometrial cancer and a comparable safety for high-risk patients, including those with older age or significant comorbidities. These findings support the use of MIS approaches as viable options across diverse risk groups, in line with FIGO 2023.


 

Zusammenfassung

Zielsetzung

Der Einsatz minimalinvasiver Chirurgie (MIC) zur Behandlung von Endometriumkarzinomen bietet Vorteile im Vergleich zur laparotomischen Behandlung, obwohl es weiterhin Bedenken hinsichtlich der onkologischen Sicherheit bei Hochrisiko-Tumoren und der Umsetzbarkeit bei Patientinnen mit signifikanten Komorbiditäten gibt. Diese Studie untersucht die perioperativen und Langzeitergebnisse von MIC und vergleicht sie anhand der FIGO-2010- und -2023-Klassifizierungen mit den Ergebnissen offener Chirurgie in einer Kohorte aus einem Referenzzentrum der Tertiärversorgung.

Methoden

Es handelt sich hier um eine retrospektive Analyse perioperativer Ergebnisse sowie der Rückfall- und Überlebensraten nach chirurgischen Eingriffen zur Behandlung von Endometriumkarzinom (2000–2021) in einem Ausbildungszentrum der ESGO und Referenzzentrum der Tertiärversorgung in Deutschland. Bei 760 Patientinnen wurde eine Hysterektomie durchgeführt, und für 330 dieser Patientinnen standen ausreichende Daten zur Risikoklassifizierung (ohne molekulare Diagnostik) zur Verfügung.

Ergebnisse

Mehr als ein Drittel der Patientinnen waren 70 Jahre alt oder älter, und ungefähr die Hälfte der Patientinnen hatte Adipositas. Ein hoher Anteil von ihnen wies auch Komorbiditäten wie Hypertonie oder Diabetes mellitus auf. MIC wies günstige perioperative Ergebnisse sowohl bei Niedrigrisiko- als bei auch Hochrisiko-Patientinnen auf. Die Überlebensanalyse zeigte bessere Ergebnisse für MIC bei Niedrigrisiko-Patientinnen (5-Jahres-RFÜ: 79,8% vs. 59,2%, p = 0,035; GÜ: 83,8% vs. 58,0%, p = 0,010) bzw. mit FIGO-2023-Stadium-I-Erkrankung (GÜ: p = 0,014). Bei Hochrisiko-Tumoren war die onkologische Sicherheit von MIC mit der Sicherheit eines offenen Eingriffs vergleichbar (5-Jahres-RFÜ: 60,5% vs. 54,3%, p = 0,506; GÜ: 67,5% vs. 58,3%, p = 0,416), wie auch bei Patientinnen mit FIGO-2023-Stadien-II- (RFÜ, p = 0,453; GÜ, p = 0,378) bzw. -III-Erkrankung (RFÜ, p = 0,419; GÜ, p = 0.850).

Schlussfolgerung

MIC wies bessere Ergebnisse bei Patientinnen mit Niedrigrisiko-Endometriumkarzinomen und eine mit offener Chirurgie vergleichbare Sicherheit bei Hochrisiko-Patientinnen auf, auch bei älteren Patientinnen oder Patientinnen mit signifikanten Komorbiditäten. Die Ergebnisse dieser Studie unterstützen den Einsatz von MIC-Verfahren als praktikable Option zur Behandlung verschiedener Risikogruppen in Übereinstimmung mit FIGO 2023.


 

Keywords

endometrial cancer - minimally invasive surgery - high risk cases - laparoscopy - laparotomy

Schlüsselwörter

Endometriumkarzinom - minimalinvasive Chirurgie - Hochrisiko-Patientinnen - Laparoskopie - Laparotomie
Key Messages

What is already known on this topic

Minimally invasive surgery (MIS) is known to reduce blood loss, shorten hospital stays and minimize postoperative complications in endometrial cancer patients compared to open surgery. However, its effectiveness, especially for high-risk patients in tertiary referral centers, has been debated due to concerns about oncological safety.

What this study adds

This study shows that in expert center settings MIS does not only provide superior perioperative outcomes for all endometrial cancer patients but also has better survival rates for low-risk patients and comparable outcomes for high-risk patients, even for those with advanced age and comorbidities, under the FIGO 2023 risk stratification.

How this study might affect research, practice, or policy

The findings support including MIS in treatment guidelines for high-risk endometrial cancer and advocate its use even in complex cases typical for tertiary centers. This could shift clinical practices further towards a more frequent use of MIS, guiding referrals to expert centers for optimized patient outcomes based on individualized risk profiles.

Introduction

420368 new cases of endometrial cancer and 97723 deaths were registered in 2020 [11]. Over the last 30 years, the incidence of endometrial cancer increased by 132%, primarily sustained by the increasing prevalence of obesity and the global population’s advancing age [22] [33] [44].

Management of endometrial cancer has undergone transformative changes. According to the National Guidelines, total hysterectomy with bilateral salpingo-oophorectomy and surgical staging/debulking is the mainstay of treatment. However, it will be necessary to determine which surgical approach is the most suitable and safest based on oncological outcomes [55].

Laparoscopic surgery is widely used in gynecologic cancers, offering a minimally invasive alternative with benefits such as reduced morbidity and faster recovery. Evidence shows that it provides advantages over laparotomy including less blood loss, fewer complications, a quicker recovery, and shorter hospital stays. Following the National Guidelines, a laparoscopic approach is deemed safe for low-risk endometrial cancer, although its effectiveness for high-risk tumors remains uncertain [44] [66] [77] [88].

To provide meaningful insights for the ongoing discussion, our study carried out a comprehensive retrospective analysis of perioperative and long-term outcomes of endometrial cancer surgery at Jena University Hospital, covering the period from 2000 to 2021. Our center is the main referral center for complex cases in Thuringia in central Germany, which has a population of two million. While surgery in younger, healthy women is performed in secondary care hospitals, our cohort mainly comprises older patients with comorbidities.

Furthermore, we incorporated both the International Federation of Gynecology and Obstetrics (FIGO) 2010 and FIGO 2023 classifications into our analysis to permit our findings to be compared with data from other studies. We aimed to assess the implications of evolving risk and staging criteria on treatment outcomes to offer a nuanced understanding of their impact on clinical practice which in the future will be developed further using molecular risk markers [99] [1010] [1111] [1212].


 

Materials and Methods

Study design

The study was a retrospective investigation of surgical outcomes in patients undergoing interventions for endometrial cancer between 15/09/2000 and 16/12/2021 in the department of gynecology at Jena University Hospital, a tertiary referral center and European Society of Gynaecological Oncology (ESGO) training center. Throughout the long study period, the treatment of patients adhered to the standards set by national and European guidelines then in force [88] [1313]. Since 1996, it has been common practice at our center to offer and perform minimally invasive surgery for endometrial cancer, including pelvic and paraaortic lymphadenectomy (levels 1 through 4), with informed patient consent, although this was not widely practiced in Germany at the time. Our study cohort included adult women diagnosed with early-stage endometrial cancer without metastatic disease. Patients underwent either laparoscopic assisted vaginal hysterectomy (LAVH) or, from 2005, vaginal assisted laparoscopic hysterectomy (VALH) with bilateral salpingo-oophorectomy (BSO), as developed by IBR and team. The procedure began with laparoscopy, peritoneal washing, occlusion of the fallopian tubes, and thorough inspection of the abdomen, peritoneal surfaces, and pelvic/para-aortic lymph nodes. Adnexa were separated, the uterine artery was coagulated and transected, and the bladder was dissected from the uterus. The patient was placed in the lithotomy position, and the uterus was removed vaginally after parametrial division avoiding cell contamination. Large uteri, such as those with fibroids, were removed via standard LAVH. The peritoneum and vaginal cuff were closed. Laparoscopic surgery was only indicated when standard preoperative sonographic evaluation ensured that the largest uterine diameter did not exceed 10 cm. Vaginal morcellation during uterine retrieval was performed, where necessary, in a manner that ensured no tumor cell contamination occurred within the abdominal cavity. TLH was reserved for benign conditions.

Cases referred to our tertiary center exhibited complexities such as high-risk histologic subtypes, diagnostic staging uncertainties requiring advanced imaging or pathology review, genetic predispositions needing specialist counseling and management, complex surgical needs, and significant comorbidities. A trained gynecologic oncologist with extensive experience in minimally invasive surgery was part of the surgical team, ensuring adherence to international oncologic care standards.


 

Data collection

Demographic and tumor characteristics, basic clinical data, treatment modalities, perioperative course, and recurrence and survival data were retrieved retrospectively from clinical records and tumor center documentation. Intraoperative complications included bleeding (from the internal and external iliac arteries and veins), blood transfusion, organ injuries (bladder, intestines), nerve injury (obturator nerve), and the need for resuscitation. Postoperative complications were classified according to Clavien-Dindo [1414]. Jena University Hospital Institutional Review Board (IRB) approval for retrospective data analysis was obtained on 21/09/2021 (no. 2021–2262_1-Daten).


 

Statistical analysis

SPSS Statistical Package for the Social Sciences (SPSS) version 27 (IBM) was used for statistical calculations. Categorical variables were analyzed using chi-square test or Fisher’s exact test, while continuous variables were evaluated using students t-test or non-parametric tests, as appropriate. Survival analyses were performed using the Kaplan-Meier method, and log-rank tests were applied to compare survival distributions. Multivariate Cox regression analyses were conducted to adjust for relevant covariates. Median follow-up time was estimated by the reverse Kaplan-Meier method.


 

 

Results

We identified 939 patients who received endometrial cancer therapy in the specified period. 610 had to be excluded for the following reasons: advanced metastatic stage, no surgery performed, external hysterectomy, vaginal hysterectomy, patient non-existence in our system, data unavailable in our files or insufficient data for risk stratification (online Supplemental Fig. S1).

Of the 330 included patients, 207 were retrospectively classified as low-risk (stage IA without nodal metastasis, ≤ G2, endometrioid) and 123 as high-risk (stage ≥ IB or G3 or with nodal metastasis or with serous papillary or clear cell type) based on FIGO 2010 criteria and Gynecologic Oncology Group-99 risk assessment [1515]. Of the 207 low-risk patients, 180 underwent laparoscopy (including three cases of robotic surgery), while 27 had laparotomy. Of the 123 high-risk patients, 63 had laparoscopy (including two cases of robotic surgery), and 60 underwent laparotomic treatment. Perioperative and long-term oncologic outcomes for the two surgical approaches were analyzed separately for low- and high-risk patients.

As expected for an all-comer cohort in a tertiary care center, more than one third of the patients were 70 years old or older (low risk, 37.7%; high risk, 46.3%) and approximately half of the patients were obese (low risk, 54.5%; high risk, 46.4%). A high proportion presented with comorbidities such as hypertension (low risk, 39.6%; high risk, 48.0%) or diabetes (low risk, 18.8%; high risk, 16.3%).

Low-risk patients

Baseline characteristics for low-risk patients are shown in [Table 1Table 1]. There were no significant differences between treatment groups for most parameters, except grading. High-grade tumors were treated more often with abdominal hysterectomy (p = 0.004).

Table 1 Table 1 Baseline characteristics of low-risk (stage IA without nodal metastasis, ≤ G2, endometrioid) endometrial cancer patients (n = 207) undergoing laparoscopic or abdominal hysterectomy at Jena University Hospital between 15/09/2000 and 16/12/2021. International Federation of Gynecology and Obstetrics (FIGO) classification, version 2020.

Whole cohort

n = 207

Laparotomy

n = 27

Laparoscopy

n = 180

P value

* Obesity was defined as a body mass index (BMI) ≥ 30 according to WHO. LVSI = lymphovascular space invasion; VI = venous invasion

a Welch’s t-test; b Pearson’s chi-squared test; c t-test; d Fisher-Freeman-Halton test; e Fisher’s exact test

Age [mean years (SD)]

65.43 (10.79)

65.11 (8.07)

65.47 (11.16)

0.839a

Age ≥ 70 [n, (%)]

78 (37.7)

8 (29.6)

70 (38.9)

0.355b

BMI [Mean (SD)]

Missing: 20

32.2 (8.12)

33.48 (8.86)

32.01 (8.06)

0.403c

Myometrial invasion [n, (%)]

  • Missing

25

  • No myometrial invasion

8 (4.4)

1 (4.2)

7 (4.4)

  • Myometrial invasion < 50%

127 (69.8)

19 (79.2)

108 (68.4)

0.560d

  • Myometrial invasion > 50%

47 (25.8)

4 (16.7)

43 (27.2)

Histology [n, (%)]

  • Endometrioid

204 (98.6)

26 (96.3)

178 (98.9)

0.344e

  • Non-endometrioid

3 (1.4)

1 (3.7)

2 (1.1)

Grading [n, (%)]

  • 1

72 (34.8)

3 (11.1)

69 (38.3)

  • 2

114 (55.1)

18 (66.7)

96 (53.3)

0.004 d

  • 3

21 (10.1)

6 (22.2)

15 (8.3)

FIGO stage (2020) [n, (%)]

  • I

207 (100)

27 (100)

180 (100)

  • II

0 (0)

0 (0)

0 (0)

  • III

0 (0)

0 (0)

0 (0)

–

pTNM T [n, (%)]

  • 1

207 (100)

27 (100)

180 (100)

  • 2

0 (0)

0 (0)

0 (0)

  • 3

0 (0)

0 (0)

0 (0)

–

pTNM N [n, (%)]

  • Missing

90

  • +

0 (0)

0 (0)

0 (0)

  • –

117 (100)

22 (55)

95 (20.4)

–

LVSI [n, (%)]

  • Missing

1

  • +

3 (1.5)

1 (3.7)

2 (1.1)

0.345e

VI [n, (%)]

  • Missing

1

  • +

4 (1.9)

1 (3.7)

3 (1.7)

0.432e

Hypertension [n, (%)]

82 (39.6)

9 (33.3)

73 (40.6)

0.474b

Diabetes [n, (%)]

39 (18.8)

4 (14.8)

35 (19.4)

0.566e

Obesity* [n, (%)]

  • Missing

20

  • +

102 (54.5)

15 (60.0)

87 (53.7)

0.556b

Perioperative outcome ([Table 2Table 2]) was significantly better in the laparoscopy group with regard to operation time (214.5 ± 88.0 vs. 326.8 ± 177.6 min, p = 0.007), duration of hospitalization (6.63 ± 3.43 vs. 15.37 ± 18.23 days, p = 0.020), hemoglobin drop (1.35 ± 1.41 vs. 2.05 ± 1.24 mmol/l, p = 0.015) and postoperative complications (12.4% vs. 50%, p < 0.001).

Table 2 Table 2 Perioperative and oncologic long-term outcomes according to surgery type in low-risk (stage IA without nodal metastasis, ≤ G2, endometrioid) endometrial cancer patients (n = 207) undergoing laparoscopic or abdominal hysterectomy at Jena University Hospital between 15/09/2000 and 16/12/2021.

Whole cohort

n = 207

Laparotomy

n = 27

Laparoscopy

n = 180

P value

Duration of surgical procedure [mean min (SD)]

230.42 (111.69)

326.8 (177.6)

214.5 (88.0)

0.007 a

Median hemoglobin drop [mean mmol/l (SD)]

1.39 (0.94)

2.05 (1.24)

1.35 (1.41)

0.015 b

Duration of hospitalization [mean days (SD)]

7.79 (7.83)

15.37 (18.23)

6.63 (3.43)

0.020 a

Intraoperative complications [n, (%)]

3 (1.5)

1 (3.7)

2 (1.1)

0.345c

Postoperative complications [n, (%)]

34 (17.4)

13 (50)

21 (12.4)

< 0.001 c

Clavien-Dindo [n, (%)]

Minor

25 (73.5)

9 (69.2)

16 (76.2)

0.704c

Major

9 (26.5)

4 (30.8)

5 (23.8)

Recurrence [n, (%)]

All*

11 (5.3)

2 (7.4)

9 (5.0)

0.433d

Local

7 (3.4)

2 (7.4)

5 (2.8)

0.228c

Distant

5 (2.4)

1 (3.7)

4 (2.2)

0.506c

Death [n, (%)]

42 (20.3)

8 (29.6)

34 (18.9)

0.196e

Death after recurrence [n, (%)]

7 (3.4)

2 (7.4)

5 (2.8)

0.482c

Recurrence-free survival (RFS)

5-year survival rate [%]

77.7

59.2

79.8

0.035 f

Median survival [months], (95% CI)

172.3

86.3 (36.0–136.6)

–

HR lsc. vs. abd.

–

0.444 (0.205–0.962)

0.040 g

HR lsc. vs. abd. adj. ▽

–

0.556 (0.252–1.227)

0.146g

Overall survival (OS)

5-year survival rate [%]

81.2

58.0

83.8

0.010 f

Median survival [months]

172.3

86.3 (35.4–137.3)

–

HR lsc. vs. abd. (95% CI)

–

0.370 (0.169–0.810)

0.013 g

HR lsc. vs. abd. adj. ▽ (95% CI)

–

0.433 (0.193–0.970)

0.042 g

CI = confidence interval; HR = hazard ratio; SD = standard deviation; lsc = laparoscopic; abd. = abdominal

a Welch’s t-test; b t-test; c Fisher’s exact test; d Fisher-Freeman-Halton test; e Pearson’s chi-squared test; f log-rank test (Kaplan-Meier); g Cox regression; * one patient had local and distant recurrence; ▽ adjusted for grading.

Median follow-up for low-risk patients was 53.8 months (min 0.3, max 238.0). Local (2.8% vs. 7.4%, p = 0.228) and total recurrence rates (5.0% vs. 7.4%, p = 0.433) were comparable after laparoscopy and laparotomy ([Table 2Table 2]). Because of the advanced age and high prevalence of comorbidities in our all-comer cohort, the death rate during follow-up was high. However, disease-specific mortality was considerably lower, with no significant difference between surgical approaches (laparoscopy, 2.8%; laparotomy 7.4%; p = 0.482).

In low-risk patients (n = 207), laparoscopic hysterectomy (n = 180) demonstrated significantly favorable recurrence-free survival (RFS) rates compared with laparotomy (86.6% vs. 81.2% at 3 years, 79.8% vs. 59.2% at 5 years, and 64.5% vs. 39.5% at 10 years, p = 0.035, [Table 2Table 2] and online Supplemental Fig. S2). Similarly, overall survival (OS) rates were superior, reaching 89.7% vs. 81.2% at 3 years, 83.8% vs. 58.0% at 5 years, and 66.4% vs. 38.7% at 10 years (p = 0.010, [Table 2Table 2] and online Supplemental Fig. S2). Because the surgery groups showed differences in tumor grading, multivariate Cox regression analysis adjusting for grading was performed. The adjusted HR was 0.556 (95% CI 0.252–1.227) for RFS and 0.433 (95% CI 0.193–0.970) for OS ([Table 2Table 2]), confirming better survival after laparoscopic treatment.


 

High-risk patients

In high-risk patients, baseline characteristics such as age, body mass index, and comorbidities did not show a significant difference between surgery types ([Table 3Table 3]). However, the laparotomy approach was preferably conducted in cases with non-endometrioid histology (p = 0.039), higher tumor stage (p = 0.010) or nodal involvement (< 0.001).

Table 3 Table 3 Baseline characteristics of high-risk (stage ≥ IB or G3 or with nodal metastasis or serous papillary or clear cell type, no distant metastasis) endometrial cancer patients (n = 123) undergoing laparoscopic or abdominal hysterectomy at Jena University Hospital between 15/09/2000 and 16/12/2021. International Federation of Gynecology and Obstetrics (FIGO) classification, version 2020.

Whole cohort

(n = 123)

Laparotomy

(n = 60)

Laparoscopy

(n = 63)

P value

* Obesity was defined as a body mass index (BMI) ≥ 30 according to the WHO.

LVSI = lymphovascular space invasion; VI = venous invasion

a t-test; b Pearson’s chi-squared test; c Fisher-Freeman-Halton test

Age [Mean (SD)]

66.21 (11.64)

64.94 (1.54)

67.55 (1.41)

0.215a

Age ≥ 70 [n, (%)]

57 (46.3)

32 (53.3)

25 (39.7)

0.129b

BMI [Mean (SD)]

Missing n = 11

31.1 (8.2)

31.17 (1.02)

30.94 (1.14)

0.878a

Myometrial invasion [n, (%)]

  • Missing

31

  • No myometrial invasion

1 (1.1)

1 (2.4)

0 (0)

  • Myometrial invasion < 50%

31 (33.7)

17 (40.5)

14 (28)

  • Myometrial invasion > 50%

60 (65.2)

24 (57.1)

36 (72)

0.154c

Histology [n, (%)]

  • Endometrioid

94 (76.4)

41 (68.3)

53 (84.1)

  • Non-endometrioid

29 (23.6)

19 (31.7)

10 (15.9)

0.039 b

Grading [n, (%)]

  • 1

6 (4.9)

3 (5)

3 (4.8)

  • 2

33 (26.8)

13 (21.7)

20 (31.7)

  • 3

84 (68.3)

44 (73.3)

40 (63.5)

0.425c

FIGO stage (2020) [n, (%)]

  • I

40 (32.5)

12 (20)

28 (44.4)

  • II

30 (24.4)

11 (18.3)

19 (30.2)

  • III

53 (43.1)

37 (61.7)

16 (25.4)

< 0.001 b

pTNM T [n, (%)]

  • 1

53 (43.1)

21 (35)

32 (50.8)

  • 2

38 (30.9)

16 (26.7)

22 (34.9)

  • 3

32 (26)

23 (38.3)

9 (14.3)

0.010 b

pTNM N [n, (%)]

  • Missing

19

  • +

40 (38.5)

30 (55)

10 (20.4)

< 0.001 c

LVSI [n, (%)]

  • Missing

24

  • +

43 (43.4)

23 (50)

20 (37.7)

0.220b

VI [n, (%)]

  • Missing

27

  • +

13 (13.5)

9 (19.6)

4 (8.0)

0.098b

Hypertension [n, (%)]

  • +

59 (48.0)

31 (51.7)

28 (44.4)

0.423b

Diabetes [n, (%)]

  • +

20 (16.3)

12 (20)

8 (12.7)

0.273b

Obesity* [n, (%)]

  • Missing

11

  • +

52 (46.4)

27 (50.9)

25 (42.4)

0.364b

Like the results observed in low-risk patients, the perioperative outcome was superior for laparoscopically treated high-risk patients compared to patients who underwent laparotomy ([Table 4Table 4]). The difference was significant for the duration of hospitalization (8.87 ± 5.07 vs. 14.98 ± 7.22 days, p < 0.001) as well as for postoperative complications (24.1% vs. 77.8%, p < 0.001). In contrast to open surgery, minor postoperative complications occurred only in 24.1% of patients after laparoscopy and no major complications were observed.

Table 4 Table 4 Perioperative and oncologic long-term outcomes according to surgery type in high-risk (stage ≥ IB or G3 or with nodal metastasis or serous papillary or clear cell type, no distant metastasis) endometrial cancer patients (n = 123) undergoing laparoscopic or abdominal hysterectomy at Jena University Hospital between 15/09/2000 and 16/12/2021.

Whole cohort

N = 123

Laparotomy

N = 60

Laparoscopy

N = 63

P value

CI = confidence interval; HR = hazard ratio; SD = standard deviation; lsc = laparoscopic; abd. = abdominal

a Welch’s t-test; b t-test; c Fisher’s exact test; d Pearson’s chi-squared test; e log-rank test (Kaplan-Meier); f Cox regression

* 4 patients had local and distant recurrence, ▽ adjusted for histology, tumor stage, and nodal status.

Duration of surgical procedure [min]

308.70 (125.37)

303.0 (109.2)

314.1 (140.1)

0.683a

Median hemoglobin drop [mmol/l]

1.29 (1.33)

1.24 (1.81)

1.06 (1.74)

0.587b

Duration of hospitalization [days]

11.88 (6.91)

14.98 (7.22)

8.87 (5.07)

< 0.001 a

Intraoperative complications [n, (%)]

14 (11.6)

10 (16.7)

4 (6.6)

0.082c

Postoperative complications [n, (%)]

56 (50)

42 (77.8)

14 (24.1)

< 0.001 d

Clavien-Dindo [n, (%)]

Minor

50 (90.9)

37 (88.1)

13 (100)

0.324c

Major

5 (9.1)

5 (11.9)

0

Recurrence [n, (%)]

All*

22 (17.8)

8 (13.3)

14 (22.2)

0.102c

Local

11 (8.9)

6 (10)

5 (7.9)

0.689c

Distant

15 (12.2)

4 (6.7)

11 (17.5)

0.067c

Death [n, (%)]

46 (37.4)

22 (36.7)

24 (38.1)

0.870c

Death after recurrence [n, (%)]

16 (13.0)

5 (8.3)

11 (17.5)

0.100c

Recurrence-free survival (RFS)

5-year survival rate [%]

57.6

54.3

60.5

0.506e

Median survival [months]

72.7 (43.8–101.5)

72.7 (2.1–143.2)

83.2 (42.4–123.9)

HR lsc. vs. abd.

–

0.831 (0.482–1.434)

0.507f

HR lsc. vs. abd. adj. ▽

–

1.166 (0.577–2.355)

0.669f

Overall survival (OS)

5-year survival rate [%]

63.2

58.3

67.5

0.416e

Median survival [months]

107.0 (79.1–134.9)

98.7 (33.1–164.3)

107.0 (62.6–151.4)

HR lsc. vs. abd. (95% CI)

–

0.786 (0.440–1.405)

0.417f

HR lsc. vs. abd. adj. ▽ (95% CI)

–

1.110 (0.524–2.343)

0.785f

Median follow-up for high-risk patients was 70.8 months (min 0.4, max 224.6). There were no significant differences in local (7.9% vs. 10%, p = 0.689) and total recurrence rates (22.2% vs. 13.3%, p = 0.102) and total (38.1% vs. 36.7%, p = 0.870) and disease-specific death rates (17.5% vs. 8.3%, p = 0.100) after laparoscopy compared to laparotomy in high-risk patients ([Table 4Table 4]).

In the high-risk patients, laparoscopic procedures (n = 63) and open surgery demonstrated comparable 3, 5, and 10-year RFS (65.5% vs. 57.9%, 60.5% vs. 54.3%, and 38.9% vs. 35.4%, respectively; p = 0.506, [Table 4Table 4] and online Supplemental Fig. S3) and OS rates (70.1% vs. 62.0% at 3 years, 67.5% vs. 58.3% at 5 years, and 44.9% vs. 41.3% at 10 years; p = 0.416, [Table 4Table 4] and online Supplemental Fig. S3). To adjust for the observed differences in histology, tumor stage, and nodal involvement, multivariate Cox regression analysis was performed. The adjusted HR was 1.166 (95% CI 0.577–2.355) for RFS and 1.110 (95% CI 0.524–2.343) for OS, indicating equivalency of the laparoscopic approach with regard to long-term outcome.


 

FIGO classification 2023

Long-term outcomes were also analyzed based on the new FIGO 2023 classification which incorporates risk status into FIGO stages ([Table 5Table 5]) [1111] [1212]. For FIGO stage I, the laparoscopic approach showed superior oncologic outcomes with 5-year RFS and OS rates of 80.2% vs. 54.3% and 82.7% vs. 54.3%, respectively. In FIGO stages II and III, outcomes were comparable, with stage II showing 5-year RFS and OS rates of 67.1% vs. 60.3% and 77.8% vs. 64.0%, and stage III displaying rates of 40.1% vs. 49.1% for RFS and 47.7% vs. 52.5% for OS. These data demonstrate the prognostic value of the FIGO 2023 staging system and confirm the results reported above, showing the superiority of laparoscopy for the treatment of low-risk tumors and equivalency for high-risk endometrial cancer.

Table 5 Table 5 Recurrence-free and overall survival of endometrial cancer patients (n = 330) according to surgery type stratified according to the International Federation of Gynecology and Obstetrics (FIGO) 2023 classification (excluding molecular diagnostics). Patients underwent laparoscopic or abdominal hysterectomy at Jena University Hospital between 15/09/2000 and 16/12/2021. Advanced metastatic stages were excluded. Estimated with the Kaplan-Meier method.

Whole cohort

Laparotomy

Laparoscopy

P value*

CI = confidence interval; OS = overall survival; RFS = recurrence-free survival

* Log-rank test.

FIGO I

n

188

21

167

0.030

RFS rate [%]

3-year

85.1

81.4

85.5

5-year

78.0

54.3

80.2

10-year

64.6

36.2

67.3

Median RFS [months]

(95% CI)

172.3

86.3

(45.2–127.5)

–

OS rate [%]

3-year

87.3

81.4

88.0

0.014

5-year

80.2

54.3

82.7

10-year

67.2

36.2

70.2

Median OS [months]

(95% CI)

–

86.3

(46.5–126.1)

–

FIGO II

n

84

28

56

0.453

RFS rate [%]

3-year

74.6

67.8

77.8

5-year

65.1

60.3

67.1

10-year

42.2

50.3

41.9

Median RFS [months]

(95% CI)

101.3

(71.1–131.6)

–

107.0

(75.9–138.1)

OS rate [%]

3-year

79.6

72.0

83.5

0.378

5-year

73.5

64.0

77.8

10-year

43.0

64.0

42.5

Median OS [months]

(95% CI)

114.0

(106.1–121.8)

–

114.0

(111.2–116.8)

FIGO III

n

51

35

16

0.419

RFS rate [%]

3-year

46.2

49.1

40.1

5-year

46.2

49.1

40.1

10-year

31.7

35.1

26.7

Median RFS [months]

(95% CI)

26.3

(0–78.6)

27.1

(0–126.1)

22.5

(0–45.7)

OS rate [%]

3-year

50.7

52.5

47.7

0.850

5-year

50.7

52.5

47.7

10-year

41.0

37.5

47.7

Median OS [months]

(95% CI)

98.7

(0.3–197.1)

98.7

(0–199.3)

26.3

(0–169.0)

 

 

Discussion

Summary of main results

This retrospective analysis of 330 endometrial cancer patients treated between 2000 and 2021 aimed to evaluate the perioperative and oncologic outcome of laparoscopic versus laparotomic surgical approaches, stratified by risk factors. Our data show that recurrence-free and overall survival after laparoscopic surgery was superior in patients with low-risk endometrial cancer and comparable in patients with high-risk tumors. These results were additionally confirmed after re-classification of patients according to FIGO 2023. Irrespective of risk group, patients had significantly fewer postoperative complications after laparoscopy, resulting in shorter hospital stays. The results indicate that minimally invasive surgery (MIS) is advantageous even in complex cases, as our cohort contained a high proportion of patients of advanced age, with obesity and relevant comorbidities.


 

Results in the context of published literature

The selection of the optimal surgical procedure for endometrial cancer remains a topic of debate, particularly concerning the efficacy and outcomes of laparoscopic versus laparotomic interventions in high-risk patients [1616]. Laparoscopy offers several perioperative benefits, including shorter recovery times and fewer complications, suggesting its potential as a preferred surgical method even for high-risk endometrial cancer patients.

A 2021 Korean population-based cohort study involving 5065 patients who underwent hysterectomy after a diagnosis of endometrial cancer showed that minimally invasive procedures were associated with fewer operative complications, shorter hospital stay, and lower costs [1717]. A randomized multicenter trial from the Gynecologic Oncology Group (GOG) found no significant difference between laparoscopy and laparotomy regarding intraoperative complications. However, laparoscopy was found to be a safer approach in terms of postoperative complications, with grade two or higher complications being more common in the laparotomy group (21% vs. 14%) [1818]. A meta-analysis of 22 studies revealed that patients with endometrial cancer undergoing laparoscopic or robotic surgery experienced fewer complications in comparison with the laparotomy group [1919]. In contrast, a Cochrane review from 2018 showed that the overall rates of severe postoperative complications did not differ significantly between the two methods [2020].

Our study confirms these previously reported advantages of MIS and further supports the feasibility and safety of MIS in a tertiary referral center. These benefits persist even in a population often considered at higher surgical risk, supporting the expansion of MIS in routine clinical practice. While tertiary and certified centers often manage a higher proportion of elderly patients and those with comorbidities, as reflected in our cohort, recent evidence suggests that this is not a universal trend. A large German cohort study [2121] found that certified cancer centers may also treat a higher proportion of younger patients and patients with early-stage disease, potentially due to differences in referral patterns and treatment centralization. This highlights the heterogeneity of patient populations across different hospital types, reinforcing the need for nuanced analysis when comparing treatment outcomes. Laparoscopic surgeries for endometrial cancer have been routinely performed at our center since 1996, indicating that there was no learning curve during the study period. Furthermore, previous large-scale studies, such as the Danish national cohort study [2222] and the recent registry data from Papathemelis et al. [2323], have already shown superior survival outcomes with MIS compared to open surgery. Our study contributes additional data specific to a high-risk referral center population, reinforcing the evidence supporting the oncologic safety of MIS even in subgroups often managed with laparotomy.

Regarding oncological safety, our data indicate no significant differences in the risk of relapse (local or distant) between laparoscopy and laparotomy in both high-risk and low-risk groups. Most literature supports our findings, showing no statistically significant difference in recurrence rates between surgical approaches in low-risk and high-risk patients. For example, a study including 419 patients who were treated between 2011 to 2017 found no statistically significant difference between low-risk and high-risk patients in laparoscopy or laparotomy groups regarding the cumulative recurrence rates [2323]. However, some studies have reported different results. A retrospective analysis of an Austrian group compared laparoscopic versus open surgery for endometrioid endometrial cancers and found no significant difference in recurrence rates and patient survival in stage I but noted higher recurrence rates in patients with stage II disease after laparoscopic approaches. This emphasizes the importance of considering stage-specific outcomes [2424].

The laparoscopic approach showed significantly better OS and RFS rates compared to open hysterectomy in our analysis. These results, like many in the literature [1717] [2323] [2424] [2525], suggest that a laparoscopic approach is the superior option for the surgical treatment of low-risk endometrial cancer.

Regarding high-risk patients, laparotomy was preferred in our cohort in some cases, based on histology, tumor stage, and nodal involvement. However, the long-term survival of high-risk endometrial cancer patients after laparoscopic surgery was not significantly different compared to the open abdominal approach, even after adjustment for these confounding factors.

Literature analyzing oncological outcomes for high-risk endometrial cancer patients treated with laparoscopy is limited [2626] [2727] [2828] [2929] [3030] [3131] [3232]. The scarcity of literature on this topic is evident in the lack of strong recommendations in European and national guidelines [55] [1313]. Remarkably, in the aforementioned studies, patients with high-risk endometrial cancer did not exhibit worse oncological outcomes after MIS compared to laparotomy.

The FIGO 2023 classification redefined disease stages, likely influencing therapeutic choices. To our knowledge, this is one of the first studies to analyze DFS and OS outcomes using FIGO 2023. Like our results for low-risk patients, we observed better survival rates after laparoscopic surgery for stage I tumors, suggesting that MIS remains oncologically safe for this subgroup under the new staging system. For stages II and III, despite the increased complexity, laparoscopic procedures yielded 5-year RFS and OS rates comparable to those with laparotomy, highlighting its viability even in more advanced stages of disease excluding extensive peritoneal carcinomatosis. These results suggest that the revised FIGO staging does not alter the established role of MIS, but future studies incorporating molecular classification are needed to assess whether additional refinements in staging criteria might further impact surgical decision-making.

In this study, we observed a 5-year OS rate of 83.8% for low-risk endometrial cancer patients undergoing MIS at a tertiary referral center. Compared to the Swedish population-based cohort (2005–2014 [3333]), which reported a 5-year net survival of about 86% for low-risk patients, our slightly lower survival rate can be attributed to the older age and higher comorbidity burden in our cohort, reflecting our center’s management of more complex cases. In contrast, the Swedish cohort, with centralized treatment and fewer selection biases, represents a more generalized population. Notably, for high-risk patients, our OS of 67.5% for MIS aligns well with the 53% to 59% range of the Swedish cohort, showing that MIS can achieve comparable outcomes even in more complex cases typical of a tertiary referral setting.


 

Strengths and weaknesses

Potential limitations include the retrospective nature of the study, variation in the surgical team over the study period, and the inherent biases associated with observational analyses. A key limitation is the selection bias introduced by including one-third of the initial patient cohort. The exclusion of patients with incomplete data or those treated in other centers may have impacted the validity of our results. Additionally, the exclusion of patients with advanced-stage disease or those not undergoing surgery may have influenced the observed survival outcomes. Nevertheless, our study provides a well-characterized patient population from a tertiary referral center and offers valuable findings. Efforts were made to mitigate these limitations through controlled data collection and appropriate statistical analysis. We acknowledge that survival analysis, particularly comparisons between laparotomy (n = 27) and laparoscopy (n = 180) in low-risk patients, is limited by the disparity in sample size. While our findings suggest a survival benefit for MIS, the small number of patients in the laparotomy group requires careful interpretation of results.


 

Implications for practice and future research

Laparoscopic surgery is a viable option for advanced stage disease and patients with comorbidities, offering comparable oncological safety, reduced surgical morbidity, and faster recovery, which facilitates timely adjuvant therapy. Our study highlights the importance of risk stratification, including use of the FIGO 2023 classification, to guide surgical decisions [3434] [3535]. Prospective trials should assess how FIGO 2023 influences lymph node dissection and impacts survival, whether MIS facilitates earlier adjuvant therapy, and confirm the safety and efficacy of MIS in patients with comorbidities.


 

 

Conclusion

Given the benefits of improved recovery and shorter hospital stay along with comparable oncological safety, a laparoscopic approach should be considered as a valuable therapeutic option for high-risk endometrial cancer patients and those with significant comorbidities.


 

Supplementary Material

  • Supplemental Fig. S1: Flowchart for inclusion and exclusion of patients. International Federation of Gynecology and Obstetrics (FIGO) classification, version 2020.

  • Supplemental Fig. S2: Recurrence-free survival (A) and overall survival (B) Kaplan-Meier curves according to the surgical approach used for low-risk (stage IA without nodal metastasis, ≤ G2, endometrioid) endometrial cancer patients (N = 207) undergoing laparoscopic or abdominal hysterectomy at Jena University Hospital between 15/09/2000 and 16/12/2021.

  • Supplemental Fig. S3: Recurrence-free survival (A) and overall survival (B) Kaplan-Meier curves according to the surgical approach used for high-risk (stage ≥ IB or G3 or with nodal metastasis or serous papillary or clear cell type, no distant metastasis) endometrial cancer patients (N = 123) undergoing laparoscopic or abdominal hysterectomy at Jena University Hospital between 15/09/2000 and 16/12/2021.


 

Previous Presentation

Part of the work was exhibited as a poster presentation at the 65th Congress of the German Society for Gynecology and Obstetrics (DGGG) on October 18, 2024 in Berlin, Germany (Abstract No. 670).


 

Statements

Approval of the local ethics committee was obtained for retrospective data research on September 21, 2021 (No. 2021–2262_1-Daten).

No special funding was obtained by the authors for this study.

Data are available upon reasonable request.


 

 

Contributorsʼ Statement

Study concepts: Ingo B. Runnebaum; Study design: Ingo B. Runnebaum; Data acquisition: Maya Ehab Hassan, Nikolaus Gaßler; Quality control of data and algorithms: Valentina Auletta, Angela Kather; Data analysis and interpretation: Maya Ehab Hassan, Valentina Auletta, Angela Kather, Ingo B. Runnebaum; Statistical analysis: Maya Ehab Hassan, Angela Kather; Manuscript preparation: Valentina Auletta, Angela Kather, Maya Ehab Hassan, Ingo B. Runnebaum; Manuscript editing: Valentina Auletta, Angela Kather, Davit Bokhua; Manuscript review: Ingo B. Runnebaum, Davit Bokhua.

Conflict of Interest

Ingo B. Runnebaum: Member of Uterus and Ovary Commissions of the AGO (Working Group on Gynecological Oncology) within the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG), Co-author for S3 guideline on Endometrial Carcinoma (Germany) and S3 guideline on Ovarian Tumors (Germany). The other authors declare no conflicts of interest.

Acknowledgement

The authors thank Lydia Kirstan and Beate Ludwig for assistance with data acquisition.

Supplementary Material


Correspondence

Prof. Dr. med. Dr. h.c. Ingo B. Runnebaum, MD, MBA
Department of gynecology and reproductive medicine, Jena University Hospital
Am Klinikum 1
07747 Jena
Germany   

Publication History

Received: 03 January 2025

Accepted after revision: 10 April 2025

Article published online:
19 May 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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