Multicenter study comparing oncologic outcomes after lymph node assessment via a sentinel lymph node algorithm versus comprehensive pelvic and paraaortic lymphadenectomy in patients with serous and clear cell endometrial carcinoma

doi:10.1016/j.ygyno.2019.11.002

Gynecologic Oncology

Volume 156, Issue 1, January 2020, Pages 62-69

https://doi.org/10.1016/j.ygyno.2019.11.002 Get rights and content

Highlights

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Overall survival in non-endometrioid endometrial carcinoma appears uncompromised using a sentinel lymph node algorithm.
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With negative nodes, recurrence-free survival is shorter with a sentinel node algorithm, but overall survival is similar.
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Lymphatic recurrences do not appear increased with sentinel lymph node assessment in non-endometrioid endometrial carcinoma.

Abstract

Objectives

To compare survival after nodal assessment using a sentinel lymph node (SLN) algorithm versus comprehensive pelvic and paraaortic lymphadenectomy (LND) in serous or clear cell endometrial carcinoma, and to compare survival in node-negative cases.

Methods

Three-year recurrence-free survival (RFS) and overall survival were compared between one institution that used comprehensive LND to the renal veins and a second institution that used an SLN algorithm with ultra-staging with inverse-probability of treatment weighting (IPTW) derived from propensity scores to adjust for covariate imbalance between cohorts.

Results

214 patients were identified (118 SLN cohort, 96 LND cohort). Adjuvant therapy differed between the cohorts; 84% and 40% in the SLN and LND cohorts, respectively, received chemotherapy ± radiation therapy. The IPTW-adjusted 3-year RFS rates were 69% and 80%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 77%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of surgical approach (SLN vs LND) with progression and death was 1.46 (95% CI: 0.70–3.04) and 0.44 (95% CI: 0.19–1.02), respectively. In the 168 node-negative cases, the IPTW-adjusted 3-year RFS rates were 73% and 91%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 86%, respectively. In this subgroup, IPTW-adjusted HR for the association of surgical approach (SLN vs LND) with progression and death was 3.12 (95% CI: 1.02–9.57) and 0.69 (95% CI: 0.24–1.95), respectively.

Conclusion

OS was not compromised with the SLN algorithm. SLN may be associated with a decreased RFS but similar OS in node-negative cases despite the majority receiving chemotherapy. This may be due to differences in surveillance.

Section snippets

Background

Serous and clear cell carcinomas of the endometrium are rare tumors associated with poor prognoses, even when diagnosed at early stages [1]. Although the use of lymphadenectomy (LND) in low-risk endometrial cancer is somewhat controversial, it is broadly accepted as part of the surgical staging algorithm in cases with serous or clear cell histology, given their propensity for early spread despite minimal myometrial invasion [[2], [3], [4]]. In a series of 50 patients with presumed stage I-II

Methods

Patients with newly diagnosed, apparently uterine-confined serous or clear cell endometrial carcinoma with any degree of myometrial invasion were identified at the Mayo Clinic and Memorial Sloan Kettering Cancer Center using institutional databases. The Memorial Sloan Kettering Cancer Center database review encompassed the years 2006 through 2013 (SLN cohort), and the Mayo Clinic database review encompassed the years 2004 through 2008 (LND cohort). During these time periods, the surgical

Overall cohort

Review of institutional databases identified 214 cases—118 in the SLN cohort and 96 in the LND cohort. Clinical and pathologic characteristics are shown in Table 1. Fifty-six patients (47.5%) in the SLN cohort and 29 (30%) in the LND cohort had no myometrial invasion. Thirty-four (29%) in the SLN cohort and 44 (46%) in the LND cohort had <50% invasion (P = 0.02). Adjuvant therapy differed between the two cohorts; 84% (99/118) in the SLN cohort and 40% (38/96) in the LND cohort received

Discussion

Patients with serous and clear cell endometrial carcinoma are at an increased risk of nodal metastasis compared to patients with endometrioid endometrial carcinoma, regardless of depth of invasion [2]. Therefore, the decision to perform a lymphadenectomy in these tumors should not be based on uterine features. We demonstrated no adverse effect on OS with the use of an SLN algorithm compared to a complete LND in patients with apparent uterine-confined serous and clear cell endometrial carcinoma.

Funding

This study was funded in part through the NIH/NCI Support Grant P30 CA008748 (Drs. Nadeem R. Abu-Rustum and Mario M. Leitao Jr).

Author contributions

Conceptualization: BAS, AM, MML.

Data Curation: BAS, ALW, MEM, JAD, SCD, WAC, GEG, NAR, AM, MML.

Formal Analysis: BAS, ALW, MEM, JAD, SCD, WAC, GEG, NAR, AM, MML.

Investigation: BAS, SCD, WAC, NAR, AM, MML.

Methodology: BAS, ALW, MEM, NAR, AM, MML.

Writing, Original Draft: BAS, MML.

Writing, Review and Editing: All authors.

Declaration of competing interests

Outside the submitted work, Dr. Abu-Rustum reports grants from Stryker/Novadaq, Olympus, and GRAIL. Outside the submitted work, Dr. Leitao is an ad hoc speaker for Intuitive Surgical, Inc. The other authors have no potential conflicts to disclose.

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Risk factors for pelvic and para-aortic lymph node metastasis in non-endometrioid endometrial cancer
2024, European Journal of Surgical Oncology
The aim of this study was to evaluate the risk factors for pelvic lymph node metastasis (LNM) and para-aortic LNM in non-endometrioid endometrial cancer (non-EEC).
A total of 283 patients with non-EEC hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were included. Various characteristics were retrospectively analyzed in relation to LNM.
Univariable and multivariable logistic regression analysis revealed cervical stromal invasion (OR = 3.441, 95% CI = 1.558–7.6, p = 0.002), myometrial invasion ≥1/2 (OR = 2.661, 95% CI = 1.327–5.337, p < 0.006), lymphovascular space involvement (LVSI) (OR = 4.118, 95% CI = 1.919–8.837, p < 0.001), positive peritoneal cytology (OR = 2.962, 95% CI = 1.344–6.530, p = 0.007), CA125 (OR = 1.002, 95% CI = 1–1.004, p = 0.026) were the independent risk factors for pelvic LNM. And myometrial invasion ≥1/2 (OR = 5.881, 95% CI = 2.056–16.427, p = 0.001), LVSI (OR = 4.962, 95% CI = 1.933–12.740, p = 0.001), adnexal (OR = 5.921, 95% CI = 2.003–17.502, p = 0.001) were the independent risk factors for para-aortic LNM. With the increase of independent risk factors, the rates of LNM were increased significantly.
Cervical stromal invasion, myometrial invasion ≥1/2, LVSI, positive peritoneal cytology, and CA125 were risk factors for pelvic LNM. Myometrial invasion ≥1/2, LVSI and involvement of the adnexa were risk factors for para-aortic LNM which could provide a good basis to help predict which non-EEC patients are at higher risk for LNM.
Sentinel node mapping in high-intermediate and high-risk endometrial cancer: Analysis of 5-year oncologic outcomes
2024, European Journal of Surgical Oncology
To assess 5-year oncologic outcomes of apparent early-stage high-intermediate and high-risk endometrial cancer undergoing sentinel node mapping versus systematic lymphadenectomy.
This is a multi-institutional retrospective, propensity-matched study evaluating data of high-intermediate and high-risk endometrial cancer (according to ESGO/ESTRO/ESP guidelines) undergoing sentinel node mapping versus systematic pelvic lymphadenectomy (with and without para-aortic lymphadenectomy). Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazard methods.
Overall, the charts of 242 patients with high-intermediate and high-risk endometrial cancer were retrieved. Data on 73 (30.1%) patients undergoing hysterectomy plus sentinel node mapping were analyzed. Forty-two (57.5%) and 31 (42.5%) patients were classified in the high-intermediate and high-risk groups, respectively. Unilateral sentinel node mapping was achieved in all patients. Bilateral mapping was achieved in 67 (91.7%) patients. Three (4.1%) patients had site-specific lymphadenectomy (two pelvic areas only and one pelvic plus para-aortic area), while adjunctive nodal dissection was omitted in the hemipelvis of the other three (4.1%) patients. Sentinel nodes were detected in the para-aortic area in eight (10.9%) patients. Twenty-four (32.8%) patients were diagnosed with nodal disease. A propensity-score matching was used to compare the aforementioned group of patients undergoing sentinel node mapping with a group of patients undergoing lymphadenectomy. Seventy patient pairs were selected (70 having sentinel node mapping vs. 70 having lymphadenectomy). Patients undergoing sentinel node mapping experienced similar 5-year disease-free survival (HR: 1.233; 95%CI: 0.6217 to 2.444; p = 0.547, log-rank test) and 5-year overall survival (HR: 1.505; 95%CI: 0.6752 to 3.355; p = 0.256, log-rank test) than patients undergoing lymphadenectomy.
Sentinel node mapping does not negatively impact 5-year outcomes of high-intermediate and high-risk endometrial cancer. Further prospective studies are warranted.
Outcomes for patients with high-risk endometrial cancer undergoing sentinel lymph node assessment versus full lymphadenectomy
2023, Gynecologic Oncology
The objective of this study was to determine the progression free survival (PFS) and overall survival (OS) among patients with high-risk endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping and dissection compared to patients who underwent pelvic +/− para-aortic lymphadenectomy (LND).
Patients with newly diagnosed high-risk EC were identified. Inclusion criteria included patients who underwent primary surgical management from January 1, 2014 to September 1, 2020 at our institution. Patients were categorized into either the SLN or LND group based on their method of planned lymph node assessment. Patients in the SLN group had dye injected followed by successful bilateral lymph node mapping, retrieval, and processing per our institutional protocol. Clinicopathological and follow-up data were extracted from patient's medical records. The t-test or Mann-Whitney test was used to compare continuous variables and Chi-squared or Fisher's exact test were used for categorical variables. Progression-free survival (PFS) was calculated from the date of initial surgery to the date of progression, death, or last follow-up. Overall survival (OS) was calculated from the date of surgical staging to the date of death or last follow-up. Three-year PFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to compare cohorts. Multivariable Cox regression models were used to assess the relationship between nodal assessment cohort and OS/PFS while adjusting for age, adjuvant therapy, and surgical approach. A result was considered statistically significant at the p < 0.05 level of significance and all statistical analysis was done using SAS version 9.4 (SAS Institute, Cary, NC).
Out of 674 patients diagnosed with EC during the study period, 189 were diagnosed with high-risk EC based on our criteria. Forty-six (23.7%) patients underwent SLN assessment and 143 (73.7%) underwent LND. No difference was observed between the two groups in regards to age, histology, stage, body mass index, tumors myometrial invasion, lymphovascular space invasion, or peritoneal washing positivity. Patients in the SLN group underwent robotic-assisted procedures more frequently than those in the LND group (p < 0.0001). The three-year PFS rate was 71.1% (95% CI 51.3–84.0%) in the SLN group and 71.3% (95% CI 62.0–78.6%) in the LND group (p = 0.91). The unadjusted hazard ratio (HR) for recurrence in the SLN versus LND group was 1.11 (95% CI 0.56–2.18; p = 0.77), and after adjusting for age, adjuvant therapy, and surgical approach, the HR for recurrence was 1.04 (95% CI 0.47–2.30, p = 0.91). The three-year OS rate was 81.1% (95% CI 51.1–93.7%) in the SLN group and 95.1% (95% CI 89.4–97.8%) in the LND group (p = 0.009). Although the unadjusted HR for death was 3.74 in the SLN vs LND group (95% CI 1.39–10.09; p = 0.009), when adjusted for age, adjuvant therapy, and surgical approach, it was no longer significant with a HR of 2.90 (95% CI 0.94–8.95, p = 0.06).
There was no difference in three-year PFS in patients diagnosed with high-risk EC who underwent SLN evaluation compared to those who underwent full LND in our cohort. The SLN group did experience shorter unadjusted OS; however, when adjusting for age, adjuvant therapy and surgical approach, there was no difference OS in patients who underwent SLN compared to LND.
Hysterectomy alone vs. hysterectomy plus sentinel node mapping in endometrial cancer: Perioperative and long-term results from a propensity-score based study
2023, European Journal of Surgical Oncology
To compare outcomes after hysterectomy and hysterectomy plus sentinel node mapping (SNM) in endometrial cancer (EC) patients.
This is a retrospective study, collecting data of EC patients treated between 2006 and 2016 in nine referral centers.
The study population included 398 (69.5%) and 174 (30.5%) patients having hysterectomy and hysterectomy plus SNM. As the results of the adoption of a propensity-score matched analysis, we selected two homogeneous cohort of patients (150 having hysterectomy only vs. 150 having hysterectomy plus SNM). The SNM group had a longer operative time, but did not correlate with length of hospital stay and estimated blood loss. Overall severe complication rates were similar between groups (0.7% in the hysterectomy group vs. 1.3% in the hysterectomy plus SNM group; p = 0.561). No lymphatic-specific complication occurred. Overall, 12.6% of patients having SNM were diagnosed with disease harboring in their lymph nodes. Adjuvant therapy administration rate was similar between groups. Considering patients having SNM, 4% of patients received adjuvant therapy on the basis of nodal status alone; all the other patients received adjuvant therapy also on the basis of uterine risk factors. Five-year disease-free (p = 0.720) and overall (p = 0.632) survival was not influenced by surgical approach.
Hysterectomy (with or without SNM) is a safe and effective method for managing EC patients. Potentially, these data support the omission of side specific lymphadenectomy in case of unsuccessful mapping. Further evidence is warranted in to confirm the role SNM in the era of molecular/genomic profiling.
Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline
2023, Practical Radiation Oncology
With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling.
The American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the (1) indications for adjuvant RT, (2) RT techniques, target volumes, dose fractionation, and treatment planning aims, (3) indications for systemic therapy, (4) sequencing of systemic therapy with RT, (5) effect of lymph node assessment on utilization of adjuvant therapy, and (6) effect of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation.
The task force recommends RT (either vaginal brachytherapy or external beam RT) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When external beam RT is delivered, intensity modulated RT with daily image guided RT is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II with high-risk histologies and those with FIGO stage III to IVA with any histology. When sequencing chemotherapy and RT, there is no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging. Data on sentinel lymph node pathologic ultrastaging status supports that patients with isolated tumor cells be treated as node negative and adjuvant therapy based on uterine risk factors and patients with micrometastases be treated as node positive. The available data on molecular characterization of endometrial cancer are compelling and should be increasingly considered when making recommendations for adjuvant therapy.
These recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer.
Evaluating long-term outcomes of three approaches to retroperitoneal staging in endometrial cancer
2022, Gynecologic Oncology
Citation Excerpt :
Additionally, well designed retrospective comparison observed that patients having SNM experienced similar oncologic outcomes compared to patients having LND for the treatment of low- and high-risk EC [20,21]. Looking both at the general population of EC and at the subgroup at high-risk EC other authors observed the non-inferiority of SNM in comparison to standard pelvic (and para-aortic) LND [11–15]. This evidence is confirmed by the pooled results of a recent meta-analysis on this issue [28], demonstrating that SNM and systematic LND are comparable in terms of detection of para-aortic nodal involvement and recurrence rates (any site and nodal recurrence).
Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment.
This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm.
Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors.
Our study highlighted that SNM provides similar long-term oncologic outcomes than LND.

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¹: Currently at The Norwegian Radium Hospital, Oslo, Norway.

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Multicenter study comparing oncologic outcomes after lymph node assessment via a sentinel lymph node algorithm versus comprehensive pelvic and paraaortic lymphadenectomy in patients with serous and clear cell endometrial carcinoma

Highlights

Abstract

Objectives

Methods

Results

Conclusion

Section snippets

Background

Methods

Overall cohort

Discussion

Funding

Author contributions

Declaration of competing interests

Gynecol. Oncol.

Gynecol. Oncol.

Obstet. Gynecol.

Gynecol. Oncol.

Gynecol. Oncol.

Gynecol. Oncol.

Gynecol. Oncol. Rep.

Eur. J. Cancer

Gynecol. Oncol.

Gynecol. Oncol.

Lancet

Gynecol. Oncol.

Lancet Oncol.