Lymph node dissection in endometrial cancer and clinical outcome: A population-based study in 5546 patients
Introduction
Endometrial cancer is the most common carcinoma of the female genital tract with over 300,000 new cases diagnosed each year worldwide [1]. Projections show an increasing incidence of this disease related to the ageing population as well as the increasing prevalence of obesity and metabolic syndromes [2]. Nodal involvement is one of the most relevant prognostic factors. Therefore, lymph node status is important to determine tumor stage and to consider adjuvant radiotherapy, chemotherapy or both [3]. Imaging techniques showed unfavorable sensitivity and specificity, thus, the current “gold standard” in the assessment of lymph node status remains comprehensive surgical staging, i.e. systematic pelvic and para-aortic lymph node dissection (LND) [4,5]. Since two randomized studies on endometrial cancer could not show a benefit in recurrence free survival (RFS) or overall survival (OS) for patients who underwent at least systematic pelvic LND compared to patients without LND, the necessity of LND is an ongoing controversy [6,7].
According to treatment guidelines and international consensus statements, a risk adopted management strategy is applied in the current clinical concept: In patients classified as low risk for lymph node involvement and recurrence (risk stratification see Table 1), with a tumor confined to the uterus, no conspicuous intra-abdominal findings and the absence of risk factors, it includes a simple hysterectomy and bilateral salpingo-oophorectomy without lymph node assessment [8,9]. In patients with high risk factors a systematic LND is recommended due to a higher prevalence of nodal involvement. In cases of intermediate/high intermediate risk factors, the best practice remains controversial, resulting in the recommendation that LND “may be” performed or not [9]. The role of systematic lymph node dissections is becoming increasingly controversial in modern oncology [[10], [11], [12]].
Furthermore, stratification criteria in endometrial cancer are often not valid pre- or intraoperatively: grading may change after final histopathologic examination, and the depth of myometrial invasion can differ compared to initial findings of preoperative imaging or fresh frozen section during surgery. The decision for adequate lymph node assessment therefore poses a fundamental challenge in the clinical management of these patients: is a “one stop” surgical approach justified or is a secondary lymph node operation after final histopathologic assessment more reliable?
Longer operative times are necessary for a systematic lymph node dissection and can be associated with considerable short- and long-time morbidity. Increased blood loss, thromboembolic complications and impairment of wound healing are more common after LND, and lymphocele formation or edema of the limb with a leg volume change over 10% in up to 34% of patients are long-term adverse events [13,14]. Therefore, the extent of surgical staging is a consideration of its associated risks: the benefit of the knowledge about nodal involvement has to be balanced against the adverse events of comprehensive surgical staging. Today, there is a wide range of surgical staging practices in endometrial cancer. The spectrum of lymph node assessment may consist of sentinel lymph node mapping, systematic pelvic or pelvic and paraaortic lymph node dissection [9,15].
Even though measurable criteria for omitting LND are lacking, it is likely that comprehensive surgical staging is rarely performed in patients with severe comorbidities. In addition to limited life expectancy, the restricted surgical treatment may also be due to a lack of adjuvant treatment. Therefore, the cohort of patients with LND may have an intrinsically favorable health status and better access to the recommended adjuvant treatment.
The aim of this study was to determine the status quo of surgical management of endometrial cancer in this large patient population. How many patients were surgically treated in accordance to the risk adopted algorithm consisting of the avoidance of an unnecessary LND in low risk patients and the performance of a reliable lymph node assessment in high risk patients. Also, how many patients with and without LND were diagnosed with loco-regional relapse or distant failure? And what is the correlation of LND and survival once the comorbidity status is considered?
Section snippets
Data collection
The Munich Cancer Registry (MCR) is a population-based clinical cancer registry representing Upper Bavaria and a region of Lower Bavaria in southern Germany [16]. The registry catchment area has grown to 4.8 million inhabitants over time. Pathology reports of solid tumors from all pathology laboratories in the catchment area are available and provide the total number of patients in the region as well as primary prognostic factors associated with the patients' disease. The clinicians provide
Results
The overall detection rate of lymph node involvement in the entire cohort of pT1 tumors was 170 of 5446 patients (3.1%). Out of all LND (n = 1906) the vast majority of 91.1% (n = 1736) had no nodal involvement and lymph node metastases were found in 8.9% (n = 170). Median lymph node count was 29 (Range 10 to ≤99). In 3188 patients with low risk factors, a LND was performed in 20.2% (n = 643). Within these patients, 1.7% (n = 11) were node-positive. In 1639 patients with intermediate/high
Discussion
This population-based cohort study presents a valid indication for the limitation of the current risk-adopted algorithm and the surgical intervention of a systematic lymph node dissection in early stage endometrial cancer. It suggests that the current concept is potentially associated with a high proportion of surgical over- and under-treatment. In 29% of the entire cohort, surgical staging differed from guideline recommendations. Treatment recommendations do not include an LND in the low risk
Abbreviations
- 95%-CI
95% Confidence interval
- DCO
Death certificate only
- ESGO
European Society of Gynecologic Oncology
- ESMO
European Society of Medical Oncology
- ESTRO
European Society for Radiotherapy and Oncology
- HR
Hazard ratio
- LND
Lymph node dissection
- MCR
Munich Cancer Registry
- NCCN
National Comprehensive Cancer Network
- OS
Overall survival
- SEER
Surveillance, Epidemiology, and End Results Program
- SLND
Sentinel Lymph Node Dissection
Conflict of interest
The authors have no conflict of interest concerning this paper.
General conflict of interest
MP reports personal fees for serving on advisory boards and lecture honoraria from AstraZeneca, Teva and Roche. SM reports grants and personal fees from Astra Zeneca, personal fees from Clovis, grants and personal fees from Medac, grants and personal fees from MSD, personal fees from Novartis, grants and personal fees from PharmaMar, grants and personal fees from Roche, personal fees from Sensor Kinesis, grants and personal fees from Tesaro, grants and personal fees from Teva, outside the
Acknowledgements
We thank all the hospitals, departments, and practitioners that participated in the documentation of the data of the Munich Cancer Registry.
Contributors
MP and MR drafting of the manuscript, MR and JE planned, performed and wrote the statistical analyses, all other authors were responsible for patient recruitment, documentation and wrote and approved the final article.
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2022, Gynecologic OncologyCitation Excerpt :Systematic lymph node dissection is suggested in patients with high-risk uterine features, but lymph node metastasis risk is approximately 20% in these patients as most of them don't have lymphatic metastasis. However, it is also important to determine nodal status for guiding the adjuvant treatment and surgical removal of lymph nodes seems like the gold standard to reveal the definitive status of lymphatic metastasis [1]. But complete lymphadenectomy is associated with many comorbidities such as neurovascular injuries and lymphedema which many patients face unnecessarily [2].
The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy
2021, European Journal of Obstetrics and Gynecology and Reproductive BiologyCitation Excerpt :If a survival effect of pelvic and paraaortic lymphadenectomy is demonstrated, patients with sentinel node metastasis could then be offered reoperation with pelvic and pararaortic lymphadenectomy, thereby still offering an advantage of introducing sentinel node staging in the population of intermediate risk endometrial cancer patients. A large German cohort study examined 1639 stage I intermediate-risk patients and demonstrated that lymphadenectomy did not alter survival or recurrence rates in agreement with the present study, an earlier retrospective study [26–31], and two randomized studies [3,4]. The authors found lymph node metastasis in 9.6% of intermediate-risk patients in line with the results of the present study.
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2021, Gynecologic OncologyCitation Excerpt :While the overall rate of lymph node sampling was different between our surgical groups (p < 0.001), the number of patients who did not receive lymph node sampling in both groups was small (Table 2). The risk of lymph node metastases in this cohort will vary depending on individual uterine risk factors [23] however it has been estimated to be approximately 10% in a large study of over 5500 women [24]. Thus, although the risk of undiagnosed stage 3 disease in our unstaged patients is small, our results must be interpreted in the context of these differing rates of staging.
Sentinel Node Mapping in Gynecologic Cancers: A Comprehensive Review
2019, Seminars in Nuclear MedicineCitation Excerpt :In this study, the detection rates for ICG for pelvic SLN, bilateral pelvic SLN, and para-aortic SLN were 96%, 80%, and 55%, respectively, with sensitivity of 91% and NPV of 99%. To conclude, LN assessment is still controversial for early-stage endometrial cancer despite several studies and a last paper with a cohort of 5546 patients published in 2019, showed that routine systematic lymphadenectomy does not improve disease-free or overall survival compared to SLN biopsy (for all histopathologic grades, including high-risk grade) and is responsible of more frequent comorbidities.136 In this context, several studies showed that SLN is a feasible procedure with accurate detection rates especially when a pericervical injection of combined [99mTc]-labeled colloids (with preoperative SPECT/CT) and ICG is performed.
- 1
The authors equally contributed to the paper.