Open Access, Peer-reviewed
pISSN 2005-0380   eISSN 2005-0399
    J Gynecol Oncol. 2023 Nov;34(6):e79. English.
    Published online Jul 07, 2023.
    https://doi.org/10.3802/jgo.2023.34.e79
    © 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology
    Original Article

    Comparison of progression-free survival outcome of sentinel node biopsy without ultrastaging versus lymphadenectomy in endometrial cancer: a propensity-matched analysis

    Dahye Lee,1,* Yoo-Na Kim,1,* Sang Hyun Cho,2 Hye soo Yoon,1 Young Tae Kim,1 Sunghoon Kim,1 and Sang Wun Kim1
      • 1Department of Obstetrics and Gynecology, Women’s Cancer Center, Yonsei Cancer Center, Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
      • 2Department of Obstetrics and Gynecology, Seoul St. Mary’s hospital, The Catholic University of Korea, Seoul, Korea.
    • Correspondence to Sang Wun Kim. Women’s Cancer Center, Yonsei Cancer Center, Institute of Women’s Life Medical Science, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea. Email: san1@yuhs.ac

      *Dahye Lee and Yoo-Na Kim have contributed equally to this work.
    Received December 28, 2022; Revised May 31, 2023; Accepted June 24, 2023.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abstract

    Objective

    We aimed to investigate the oncologic outcomes of patients with endometrial cancer who underwent sentinel lymph node (SLN) biopsy without ultrastaging compared with that of those who underwent lymphadenectomy (LND).

    Methods

    Patients with endometrial cancer who underwent staging with SLN biopsy or LND during 2006 – 2021 were analyzed using propensity score matching (PSM). SLN metastasis was examined using hematoxylin and eosin staining, without ultrastaging. Progression-free survival (PFS) was compared between the two groups before and after PSM using age, histology, and stage as covariates. Clinical variables such as recurrence patterns and lymphatic complications, were assessed.

    Results

    After excluding 213 patients who underwent validation LND with SLN biopsy, 902 were identified. The demographics of the remaining patients differed according to histology, myometrial invasion depth, and stage. Lymph node metastasis was less frequent in the SLN group than in the LND group (9.4% vs. 3.8%, p=0.004). The recurrence rates within 2 years were lower in the SLN group. The SLN group exhibited significantly superior 2-year and overall PFS than the LND group. Among patients with uterus-confined disease, overall PFS was favorable for SLN biopsy. After matching, differences in PFS were no longer observed, although the lymphocele and lymphedema rates were significantly lower in the SLN group.

    Conclusion

    In patients with endometrial cancer, SLN biopsy without ultrastaging did not compromise survival outcomes and was associated with significantly reduced lymphatic complication rates compared with LND. Therefore, SLN biopsy can be recommended for patients with endometrial cancer without definitive preoperative evidence of distant metastasis.

    Synopsis

    Survival outcomes of sentinel node (SLN) biopsy without ultrastaging and lymphadenectomy (LND) were retrospectively compared. With propensity score matching, SLN biopsy without ultrastaging demonstrated comparable survival outcomes. SLN biopsy without ultrastaging exhibited a lower rate of lymphatic complications than LND.

    Keywords
    Endometrial Neoplasms; Sentinel Lymph Node Biopsy; Lymphadenectomy; Survival; Lymphedema/Complications; Lymphocele/Complications

    INTRODUCTION

    Endometrial cancer, with an increasing incidence rate in developing countries, is the most common gynecological cancer [1]. Prognostic studies, such as those on molecular classification [2] and radiological assessment using computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound [3, 4] have been conducted to improve survival outcomes. The introduction of sentinel lymph node (SLN) mapping in 1996 was a game-changer in surgical management [5]. Previously, complete lymphadenectomy (LND), which involves removing all pelvic and para-aortic lymph nodes, was the standard surgical staging for endometrial cancer. Lymph node status not only provides prognostic information but also therapeutic and predictive implications that guide the selection of adjuvant therapy [6, 7, 8]. Accurately assessing lymph nodes during surgery helps determine whether a patient should receive chemotherapy or radiotherapy [8, 9].

    Complete LND inadvertently can cause surgical morbidities, such as lymphedema, lymphocele, and nerve injury [10, 11]. SLN mapping is an attractive alternative because it can provide equivalent information about lymph node status while sparing patients from unnecessary lymph node dissection and associated morbidities [7, 12, 13, 14]. Large-scale trials, such as the FIRES and SENTI-ENDO trials [7, 12], have demonstrated high diagnostic accuracy, sensitivity, and negative predictive value, leading to a change in the standard of care [15, 16]. SLN biopsy is increasingly being used alone, especially for patients with suspected early-stage or histologically low-risk endometrial cancer, based on current guidelines [16, 17]. However, evidence is still required for the surgical management of preoperative high-risk endometrial cancer [18, 19].

    Regarding the oncological outcomes of SLN biopsy, high-quality prospective evidence is lacking. Several retrospective studies suggested that the oncological outcomes of SLN biopsy are comparable to those of complete LND [8, 14, 20, 21], although many of these studies mostly considered patients with early-stage endometrial cancer, and their survival outcomes are immature [14, 22]. Retrospective studies also face potential bias due to the time lag between the phase of LND and introduction of SLN biopsy. Large-scale trials such as the PORTEC-3 were introduced during this time span, which could have impacted both the surgical and adjuvant aspects of patient care, potentially changing the trend of adjuvant therapy at the same time [6, 23]. Moreover, previous studies on SLN mapping outcomes were based on ultrastaging [16], which varies among centers and incurs extra costs and resources [24]. In practice, many centers have no alternative but to bypass ultrastaging and to assess SLN biopsy samples using conventional hematoxylin and eosin (H&E) staining.

    This study aimed to compare the oncological outcomes of complete LND and SLN biopsy, without ultrastaging. Progression-free survival (PFS) was compared using propensity score matching (PSM), and lymphatic complications were compared between patients with endometrial cancer who underwent SLN biopsy and a historical cohort of those who underwent LND.

    MATERIALS AND METHODS

    1. Patient selection

    We retrospectively analyzed patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I-III endometrial cancer who underwent surgical staging at Yonsei Cancer Center, Seoul, Republic of Korea, from 2006 to 2021. Patients were classified into an LND and SLN group based on the use of the SLN technique. Patients who did not undergo SLN biopsy or LND were excluded. The LND group underwent surgical staging mostly from 2006 to 2013, while the SLN group underwent surgical staging from 2014 to 2021. For a brief period since the introduction of SLN biopsy in 2014, SLN biopsy was followed by validation LND at the clinician’s discretion. Thus, patients in whom more than five non-SLNs removed as a result of undergoing both SLN biopsy and LND were excluded from the SLN group. The exclusion criteria included suspected distant organ metastasis, prior hysterectomy or LND for endometrial cancer, contraindication for indocyanine green (ICG), or history of liver disease for the SLN group. The study was approved by the Institutional Review Board (IRB) of Severance Hospital (IRB No #4–2022-0250), and the requirement for informed consent was waived owing to the retrospective design.

    2. Lymph node assessment

    All patients in the LND group underwent pelvic LND. The extent and number of removed lymph nodes in para-aortic LND were at the clinician’s discretion. Generally, para-aortic LND was performed in the following cases: 1) preoperative histology indicated high-risk, such as endometrioid grade 3, serous type, or clear cell carcinoma, or other non-endometrioid histology of any grade, 2) when preoperative imaging (CT, MRI, or positron emission tomography [PET]) revealed an enlarged lymph node or increased F-18 fluorodeoxyglucose uptake in the lymph node in the para-aortic area beyond normal physiological levels, or 3) when enlarged para-aortic lymph nodes were discovered during the surgery. SLN biopsy was performed using either one-step or two-step SLN mapping, as per the protocol detailed in a previous study [25]. The decision to omit LND in the SLN group was mainly based on the SLN algorithm of the National Comprehensive Cancer Network (NCCN) guidelines and negative findings for enlarged lymph nodes confirmed during surgery [16]. Briefly, two-step SLN detection was performed using laparoscopic or robotic platforms by injecting ICG into each cornu through an injection needle inserted at a depth of 1 cm into the bilateral uterine cornu after tubal ligation. Lymphatics drained from the uterus were identified, and biopsy of the para-aortic SLN was conducted. After completing the para-aortic SLN biopsy, ICG was injected at the 3 and 9 o'clock positions of the ectocervix at the superficial and deep cervix. ICG was injected into the cervix for one-step SLN mapping. Intraoperative SLN detection and localization were guided using the PinPoint endoscopic platform (Novadaq Technologies Inc., Toronto, ON, Canada) or robotic platform (da Vinci platform; Intuitive Surgical, Inc., Sunnyvale, CA, USA) for real-time imaging. Successful SLN mapping observed lymphatic drainage to at least one node at either side of the hemipelvis or at the para-aortic level. The harvested SLN was sent for either frozen section during the operation or permanent pathological examination at the end of surgery. No additional surgical procedures were performed even if the SLNs were positive for metastasis.

    3. Pathologic examination of lymph nodes

    The SLNs, along with the lymph nodes obtained from LND, were sliced into 2–3-mm thick pieces with longitudinal cross-sections and subjected to conventional H&E staining without ultrastaging or accompanying immunohistochemistry, following institutional protocol. Dedicated pathologists examined all removed nodes.

    4. Postoperative adjuvant treatment

    The postoperative adjuvant therapy followed the NCCN guidelines. For endometrioid or serous histology, paclitaxel 175 mg/m2 and carboplatin with an area under the curve 5 to 6 were administered for six cycles of every 3-week regimen. Adjuvant therapy for a rare histology, such as carcinosarcoma or endometrial stromal sarcoma, varied depending on the clinician’s discretion within the NCCN guidelines. The field of radiotherapy was determined according to the FIGO stage and was administered according to the NCCN guidelines, including intracavitary radiation, radiation for the whole pelvis, or for the extended abdominal area [16].

    5. Data collection

    Electronic medical records were reviewed for age at the time of diagnosis, body mass index (BMI), pathologic findings, FIGO staging, disease status during the follow-up period, date of recurrence, and date of the last follow-up of all patients. High-risk histology included endometrioid grade 3 and all non-endometrioid histologies of any grade such as clear cell carcinoma, serous carcinoma, and carcinosarcoma, and others. Low-risk histology included endometrioid grade 1 or 2.

    During the first 2 years after surgery, recurrence was assessed every 3 months using CT, MRI, or PET-CT,-confirmed by hospital radiologists. Afterward, recurrence was evaluated every 6 months. The incidence of postoperative complications related to LND, such as lymphocele and lymphedema, were calculated for each group. For lymphocele, only those ≥1 cm on CT/MRI within a year after surgery were considered. Lymphedema was diagnosed clinically when the patient required rehabilitation and medical treatment. Postoperative adjuvant therapy was administered at the clinician’s discretion, based on the NCCN guidelines. Recurrence site was determined via imaging or biopsy, classified as lymph nodes (pelvic, para-aortic, or both), vagina (stump, vault, or wall), peritoneal seeding or metastases (except nodal in the abdominal-pelvic region), distant organ metastases (such as lung or bone, and supraclavicular lymph nodes).

    6. Statistical methods

    Statistical analyses were performed using R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria). Baseline characteristics were compared using Student’s t-test for continuous variables and the χ2 test for categorical variables. PSM was performed using the ‘MatchIt’ package to adjust for differences in cohort size and baseline characteristics. Specifically, 1:1 nearest-neighbor matching was performed using the propensity score, which was estimated based on covariates such as age, histology, and FIGO stage.

    Clinical outcomes were evaluated based on PFS, including overall PFS and 2-year-PFS. PFS was compared between the LND and SLN groups before and after the matching. A Cox proportional hazards regression model was used to calculate the hazard ratio (HR) for lymph node evaluation method and other prognostic variables. In the matched cohort, the proportion of patients with nodal metastasis, recurrence rate for uterus-confined stage I or II disease, anatomical pattern of recurrence location, and postoperative complications such as lymphocele and lymphedema were investigated.

    RESULTS

    The Yonsei Cancer Center reviewed patients with endometrial cancer who underwent staging operations between 2006 and 2021. Of the 1,115 patients, 645 patients underwent LND, and 470 underwent SLN biopsy. Only 257 patients were included in the SLN group after excluding those who had undergone both SLN biopsy and LND (Fig. 1). The LND group had a higher proportion of patients with high-risk histology and deep myometrial invasion. The rate of LN metastasis was significantly higher in the LND group than in the SLN group (9.4% and 3.8%, respectively, p=0.004), although the rate of para-aortic LN metastasis was comparable between the two cohorts (4.7% and 1.9% in the LND and SLN groups, respectively). Adjuvant use was similar between the two cohorts; however, chemotherapy was more frequently implemented in the LND group. The median follow-up duration was 2.1 years for patients who underwent SLN biopsy alone and 5.3 years for those belonging to the LND cohort (Table 1, Table S1).

    Fig. 1
    Patient flow chart. Matching age, histology, and stage.
    LND, lymphadenectomy; SLN, sentinel lymph node.

    Table 1
    Patient demographics before matching

    The SLN group had a significantly lower rate of recurrence within 2 years (3.1% vs. 7.8%, p=0.006) and a superior PFS (p=0.007; Fig. 2A, Fig. S1). Based on univariate analysis with respect to overall PFS, patients who underwent SLN biopsy showed a lower HR than those who underwent LND (0.40, p=0.023) (Table S2). Multivariate analysis showed that the HR for the SLN group was lower than that in the LND group (0.44, p=0.050) (Fig. 3, Fig. S2), even after accounting for other potential factors affecting PFS.

    Fig. 2
    Overall progression-free survival of patients.
    (A) Before matching (B) Endometrial cancer either stage I or II before matching (C) After matching.

    LND, lymphadenectomy; SLN, sentinel lymph node.

    Fig. 3
    Multivariate Cox regression analysis with respect to overall progression-free survival before matching.
    BMI, body mass index; FIGO, International Federation of Gynecology and Obstetrics; MMI, myometrial invasion; LND, lymphadenectomy; OP, operation; SLN, sentinel lymph node.

    In the unmatched cohort, patients with FIGO stage I or II disease were investigated, and a trend of better overall PFS in the SLN group was observed. Among these patients, 32 had recurrences within 2 years. The 2-year recurrence rates were 2.1% (5/241) in the SLN and 4.8% (27/564) in the LND group (p=0.048). A trend of better overall PFS in the SLN group was observed, despite the lack of statistical significance (p=0.073; Fig. 2B).

    PSM was performed (Table 2, Table S3), and after matching, the 2-year recurrence rates did not differ between the SLN and LND groups (3.1% vs. 4.3%, p=0.101). There was no difference in 2-year and overall PFS (Fig. 2C, Fig. S1). No significant difference was observed between the low-risk and high-risk groups in terms of the 2-year and overall PFS rates (Figs. S3 and S4). Recurrence sites for those who experienced recurrences within 2 years are shown in Table 3. LND was associated with higher recurrence rates at the peritoneum than SLN biopsy (3.11% vs. 0.39%, p=0.019). While no significant difference in the nodal recurrence rates was observed between the two groups, LND was associated with a trend toward higher rates. Lymphatic complications were significantly lower in the SLN group than in the LND group (lymphocele: 2.3% vs. 8.9%, p=0.002; lymphedema: 0.8% vs. 4.3%, p=0.025) (Table S4).

    Table 2
    Patient demographics after matching

    Table 3
    Recurrence site analysis after matching

    DISCUSSION

    The replacement of complete LND, with SLN biopsy has become increasingly common, from low-risk to high-risk disease and suspected advanced-stage disease [14, 19, 20, 21]. In our study, we analyzed a sizable cohort of patients with endometrial cancer undergoing SLN mapping without ultrastaging and a historical cohort of patients who underwent LND. PSM was utilized to address potential biases. Our study showed a clinical trend toward improved PFS in patients who underwent SLN mapping compared with those who underwent LND. Differences in survival outcomes were no longer observed after PSM, although the rate of lymphatic complications was lower in patients who underwent SLN mapping.

    Our study examined the SLN alone with H&E staining, without ultrastaging, which is unique. Previous research has shown that ultrastaging of SLNs improves the detection of lymph node involvement in low-volume metastasis [14, 26, 27]. However, there is controversy over the oncological outcomes of detecting metastatic SLNs with ultrastaging [8, 20, 21] and necessity for adjuvant therapy in cases of isolated tumor cells found in SLNs [22, 28]. Despite these controversies, SLN biopsy with ultrastaging is recommended based on the NCCN guidelines [16]. Most previous studies on the oncologic outcomes of SLN mapping involved patients receiving ultrastaging [8, 14, 20]. In contrast, our study assessed SLNs alone with H&E staining, according to our institution’s convention. Our findings demonstrate that patients who received treatment based on SLN biopsy without ultrastaging showed a trend of low nodal recurrence and overall recurrence rates compared with those who underwent conventional LND.

    Comparing survival outcomes between SLN mapping and LND is more complex than just sample selection bias in retrospective designs. The NCCN guideline evolved from recommending full LND to SLN mapping with a transition period of validation LND before omitting LND. The transition period could span months to years, with variations in surgical techniques employed among different surgeons [29, 30]. Additionally, the trend in adjuvant therapy use has changed over the years, with increasing popularity of intracavitary radiotherapy [31, 32] and wider use of chemotherapy for stage III based on the PORTEC-3 [6].

    Previous studies have utilized statistical methods such as PSM to compare outcomes of SLN mapping and LND. One study by Bogani et al. [20] compared 3-year PFS and OS across the SLN only, SLN plus LND, and LND alone groups using SLN biopsy with ultrastaging and found no difference in outcomes. Schlappe et al. [21] also compared the outcomes of SLN biopsy with ultrastaging with those of LND using PSM and found no difference in the 3-year PFS (69% vs. 80%, p=0.320) and OS rates (88% vs. 77%, p=0.060). Differences in baseline demographics and adjuvant patterns could explain the discrepancy in PFS between Schlappe et al.’s study [21] and the current study. As practice patterns (i.e., surgical technique, injection dye and technique, and adjuvant therapy) can differ across institutions and nations, more data on SLN mapping’s survival outcome may be necessary.

    Our study not only compared outcomes in matched cohorts but also investigated survival outcomes in a subset of patients initially diagnosed with uterine-confined disease (stages I and II) to ultimately base the outcome of SLN mapping on patient outcomes. The rationale was that the diagnostic accuracy of pre- and postoperative imaging was far less than 100% [33, 34]. Furthermore, because tumors can spread to unusual lymph node locations [8, 12, 19], validation LND may lead to failed detection of nodal metastasis, and our study showed a trend toward improved outcomes in the SLN cohort compared with the unmatched cohort. This might be related to the higher rate of nodal recurrence observed in LND group. SLN mapping technique traces the lymphatic channels originating from the uterus, whereas LND non-specifically removes lymph nodes. SLN biopsy allows more accurate removal of the lymph nodes that are likely to serve as channels of lymphatic metastasis. This approach offers a more precise identification and removal of lymph nodes, potentially reducing the risk of nodal recurrence. However, the follow-up duration was shorter in the SLN group, and further follow-up is necessary to verify our findings.

    The study found that the rate of lymphatic complications was significantly lower in the SLN group than in the LND group. Previous studies on lymphatic complications reported the rate of lymphocele to be 2.6%–17.3% and that of lymphedema to be 1.3%–49.4%, regardless of the mode of surgery [11, 13, 35, 36]. In our study, the rate of lymphocele was 2.3% in the SLN group and 8.9% in the LND group and that of lymphedema was 0.8% in the SLN group and 4.3% in the LND group. Our lower complication rate compared with that of previous reports may be attributed to factors, such as patient demographics, BMI, number of lymph nodes removed, and Eastern Cooperative Oncology Group (ECOG) performance status. The median number of SLNs removed was similar to that in previous studies [13, 36]; while the median number of lymph nodes from LND removed was lower [13, 36]. Additionally, our method of counting the lymphoceles and lymphedemas may have overlooked lower-grade complications. However, despite the possibility of underestimating the incidence of lymphatic complications in both groups, our findings are consistent with those of previous studies showing lower complication rates in the SLN group [13, 35, 36].

    To expand our research on the survival and quality of life (QOL) outcomes of SLN mapping, we can focus on specific subgroups such as older patients and those with high fragility scores, which may have an impact on treatment, complications, and survival outcomes [37]. Our study primarily focused on comparing the surgical modality of SLN biopsy with that of LND, with age being the only patient fragility factor taken into account. However, further investigation into other patient factors such as ECOG performance status and personal medical history may be useful in exploring survival and QOL-related outcomes in the aging population setting. Additionally, incorporating the cancer genome atlas (TCGA) molecular classification profiles into outcome analysis, specifically in the context of SLN mapping, could be another avenue worth exploring. Previous studies have suggested that the molecular classification of endometrial cancer is associated with lymph node metastasis [38] and can influence tumor characteristics, such as mismatch repair deficiency tumors frequently found in the low segment of the uterus [39]. These molecular characteristics may also affect patient screening, radiologic or ultrasonographic imaging findings [3, 4], surgical treatment options, including whether to perform SLN biopsy or not and which specific SLN biopsy technique to utilize, as well as adjuvant therapy options [40]. Exploring these factors may lead to interesting research avenues regarding outcome and QOL studies in SLN mapping. The limitations of our study include the limited sample size and the selection bias due to its retrospective nature.-Although we attempted to correct the imbalance between the two cohorts using statistical methods, it is possible that potential confounders were incompletely addressed. Because we did not have a prospective institutional protocol for the specific details of SLN mapping, the surgical techniques could have varied among different surgeons. Moreover, our assessment of lymphocele and lymphedema was based on CT images and chart reviews.

    In conclusion, our study is one of the largest retrospective analyses of SLN mapping and the first to report on outcomes for patients who underwent SLN mapping without ultrastaging. Initially, there was a clinical trend that suggested improved PFS in patients who underwent SLN biopsy without ultrastaging compared with those who underwent LND, although this did not reach statistical significance. However, after addressing the intergroup baseline characteristic imbalance, the oncologic outcome of SLN biopsy without ultrastaging was comparable to that of LND, and patients receiving SLN mapping showed a significantly lower rate of lymphatic complications, such as lymphocele and lymphedema. Although there were differences in adjuvant treatments between the LND and SLN groups, further prospective studies are needed to confirm the survival outcomes of SLN biopsy without ultrastaging. Nevertheless, SLN biopsy without ultrastaging can be considered for every patient with endometrial cancer who does not have definitive evidence of distant metastasis on preoperative evaluation.

    SUPPLEMENTARY MATERIALS

    Table S1

    Patients with LNs harvested or metastatic at specific anatomic level before matching

    Click here to view.(38K, xls)

    Table S2

    Univariate analysis before matching

    Click here to view.(39K, xls)

    Table S3

    Patients with LNs harvested or metastatic at specific anatomic level after matching

    Click here to view.(37K, xls)

    Table S4

    Lymphatic complication after matching

    Click here to view.(36K, xls)

    Fig. S1

    Two-year progression-free survival.

    Click here to view.(384K, ppt)

    Fig. S2

    Multivariate with respect to 2-year progression-free survival before matching.

    Click here to view.(593K, ppt)

    Fig. S3

    Two-year progression-free survival in subgroup analysis after matching.

    Click here to view.(356K, ppt)

    Fig. S4

    Overall progression-free survival in subgroup analysis after matching.

    Click here to view.(355K, ppt)

    Notes

    Funding:This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI19C0481, HC21C0012).

    Conflict of Interest:No potential conflict of interest relevant to this article was reported.

    Presentation:Women’s Cancer Center, Yonsei Cancer Center, Institute of Women’s Life Medical Science,

    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Yonsei University College of Medicine

    Author Contributions:

    • Conceptualization: K.Y.N., K.S.W.

    • Data curation: L.D., K.Y.N., C.S.H., Y.H.S.

    • Formal analysis: K.Y.N., C.S.H.

    • Investigation: L.D.

    • Methodology: K.Y.N.

    • Project administration: K.S.W.

    • Resources: K.Y.T., K.S.

    • Supervision: K.Y.N., K.S.W.

    • Validation: K.S.W.

    • Writing - original draft: L.D., K.Y.N.

    • Writing - review & editing: K.Y.N.

    References

      1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209–249.
      1. Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz J, et al. Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer. Cancer 2017;123:802–813.
      1. Jacob H, Dybvik JA, Ytre-Hauge S, Fasmer KE, Hoivik EA, Trovik J, et al. An MRI-based radiomic prognostic index predicts poor outcome and specific genetic alterations in endometrial cancer. J Clin Med 2021;10:538.
      1. Bogani G, Chiappa V, Lopez S, Salvatore C, Interlenghi M, D’Oria O, et al. Radiomics and molecular classification in endometrial cancer (The ROME Study): a step forward to a simplified precision medicine. Healthcare (Basel) 2022;10:2464.
      1. Burke TW, Levenback C, Tornos C, Morris M, Wharton JT, Gershenson DM. Intraabdominal lymphatic mapping to direct selective pelvic and paraaortic lymphadenectomy in women with high-risk endometrial cancer: results of a pilot study. Gynecol Oncol 1996;62:169–173.
      1. de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, et al. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol 2019;20:1273–1285.
      1. Daraï E, Dubernard G, Bats AS, Heitz D, Mathevet P, Marret H, et al. Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study. Gynecol Oncol 2015;136:54–59.
      1. Kogan L, Matanes E, Wissing M, Mitric C, How J, Amajoud Z, et al. The added value of sentinel node mapping in endometrial cancer. Gynecol Oncol 2020;158:84–91.
      1. Holloway RW, Abu-Rustum NR, Backes FJ, Boggess JF, Gotlieb WH, Jeffrey Lowery W, et al. Sentinel lymph node mapping and staging in endometrial cancer: a Society of Gynecologic Oncology literature review with consensus recommendations. Gynecol Oncol 2017;146:405–415.
      1. Frost JA, Webster KE, Bryant A, Morrison J. Lymphadenectomy for the management of endometrial cancer. Cochrane Database Syst Rev 2017;10:CD007585
      1. Volpi L, Sozzi G, Capozzi VA, Ricco’ M, Merisio C, Di Serio M, et al. Long term complications following pelvic and para-aortic lymphadenectomy for endometrial cancer, incidence and potential risk factors: a single institution experience. Int J Gynecol Cancer 2019;29:312–319.
      1. Rossi EC, Kowalski LD, Scalici J, Cantrell L, Schuler K, Hanna RK, et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol 2017;18:384–392.
      1. Glaser G, Dinoi G, Multinu F, Yost K, Al Hilli M, Larish A, et al. Reduced lymphedema after sentinel lymph node biopsy versus lymphadenectomy for endometrial cancer. Int J Gynecol Cancer 2021;31:85–91.
      1. Buda A, Di Martino G, Restaino S, De Ponti E, Monterossi G, Giuliani D, et al. The impact on survival of two different staging strategies in apparent early stage endometrial cancer comparing sentinel lymph nodes mapping algorithm and selective lymphadenectomy: an Italian retrospective analysis of two reference centers. Gynecol Oncol 2017;147:528–534.
      1. Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer 2021;31:12–39.
      1. Abu-Rustum N, Yashar C, Arend R, Barber E, Bradley K, Brooks R, et al. Uterine neoplasms, version 1.2023, NCCN Clinical Practice Guidelines in oncology. J Natl Compr Canc Netw 2023;21:181–209.
      1. Casarin J, Multinu F, Abu-Rustum N, Cibula D, Cliby WA, Ghezzi F, et al. Factors influencing the adoption of the sentinel lymph node technique for endometrial cancer staging: an international survey of gynecologic oncologists. Int J Gynecol Cancer 2019;29:60–67.
      1. Salman L, Cusimano MC, Marchocki Z, Ferguson SE. Sentinel lymph node mapping in high-grade endometrial cancer. Curr Oncol 2022;29:1123–1135.
      1. Persson J, Salehi S, Bollino M, Lönnerfors C, Falconer H, Geppert B. Pelvic sentinel lymph node detection in high-risk endometrial cancer (SHREC-trial)-the final step towards a paradigm shift in surgical staging. Eur J Cancer 2019;116:77–85.
      1. Bogani G, Casarin J, Leone Roberti Maggiore U, Ditto A, Pinelli C, Dell’acqua A, et al. Survival outcomes in endometrial cancer patients having lymphadenectomy, sentinel node mapping followed by lymphadectomy and sentinel node mapping alone: long-term results of a propensity-matched analysis. Gynecol Oncol 2020;158:77–83.
      1. Schlappe BA, Weaver AL, McGree ME, Ducie J, Zahl Eriksson AG, Dowdy SC, et al. 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. Gynecol Oncol 2020;156:62–69.
      1. Ghoniem K, Larish AM, Dinoi G, Zhou XC, Alhilli M, Wallace S, et al. Oncologic outcomes of endometrial cancer in patients with low-volume metastasis in the sentinel lymph nodes: an international multi-institutional study. Gynecol Oncol 2021;162:590–598.
      1. Matei D, Filiaci V, Randall ME, Mutch D, Steinhoff MM, DiSilvestro PA, et al. Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer. N Engl J Med 2019;380:2317–2326.
      1. Burg LC, Hengeveld EM, In ’t Hout J, Bulten J, Bult P, Zusterzeel PL. Ultrastaging methods of sentinel lymph nodes in endometrial cancer - a systematic review. Int J Gynecol Cancer 2021;31:744–753.
      1. Kim YN, Eoh KJ, Lee JY, Nam EJ, Kim S, Kim YT, et al. Comparison of outcomes between the one-step and two-step sentinel lymph node mapping techniques in endometrial cancer. Int J Gynecol Cancer 2020;30:318–324.
      1. Kim CH, Soslow RA, Park KJ, Barber EL, Khoury-Collado F, Barlin JN, et al. Pathologic ultrastaging improves micrometastasis detection in sentinel lymph nodes during endometrial cancer staging. Int J Gynecol Cancer 2013;23:964–970.
      1. Cusimano MC, Vicus D, Pulman K, Maganti M, Bernardini MQ, Bouchard-Fortier G, et al. Assessment of sentinel lymph node biopsy vs lymphadenectomy for intermediate- and high-grade endometrial cancer staging. JAMA Surg 2021;156:157–164.
      1. García Pineda V, Hernández Gutiérrez A, Gracia Segovia M, Siegrist Ridruejo J, Diestro Tejeda MD, Zapardiel I. Low-volume nodal metastasis in endometrial cancer: risk factors and prognostic significance. J Clin Med 2020;9:1999.
      1. Matsuo K, Klar M, Khetan VU, Violette CJ, Nusbaum DJ, Muderspach LI, et al. Sentinel lymph node biopsy for stage II endometrial cancer: recent utilization and outcome in the United States. Gynecol Oncol 2022;164:46–52.
      1. Wright JD, Cham S, Chen L, Burke WM, Hou JY, Tergas AI, et al. Utilization of sentinel lymph node biopsy for uterine cancer. Am J Obstet Gynecol 2017;216:594.e1–594.13.
      1. Nout RA, Smit VT, Putter H, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet 2010;375:816–823.
      1. Shinde A, Li R, Amini A, Chen YJ, Cristea M, Dellinger T, et al. Improved survival with adjuvant brachytherapy in stage IA endometrial cancer of unfavorable histology. Gynecol Oncol 2018;151:82–90.
      1. Rockall AG, Barwick TD, Wilson W, Singh N, Bharwani N, Sohaib A, et al. Diagnostic accuracy of FEC-PET/CT, FDG-PET/CT, and diffusion-weighted MRI in detection of nodal metastases in surgically treated endometrial and cervical carcinoma. Clin Cancer Res 2021;27:6457–6466.
      1. Body N, Lavoué V, De Kerdaniel O, Foucher F, Henno S, Cauchois A, et al. Are preoperative histology and MRI useful for classification of endometrial cancer risk? BMC Cancer 2016;16:498.
      1. Diniz TP, Drizlionoks E, Faloppa CC, Menezes JN, Mantoan H, Gonçalves BT, et al. Impact of sentinel node mapping in decreasing the risk of lymphocele in endometrial cancer. Ann Surg Oncol 2021;28:3293–3299.
      1. Geppert B, Lönnerfors C, Bollino M, Persson J. Sentinel lymph node biopsy in endometrial cancer-feasibility, safety and lymphatic complications. Gynecol Oncol 2018;148:491–498.
      1. Giannini A, Di Donato V, Schiavi MC, May J, Panici PB, Congiu MA. Predictors of postoperative overall and severe complications after surgical treatment for endometrial cancer: the role of the fragility index. Int J Gynaecol Obstet 2020;148:174–180.
      1. Jamieson A, Thompson EF, Huvila J, Leung S, Lum A, Morin C, et al. Endometrial carcinoma molecular subtype correlates with the presence of lymph node metastases. Gynecol Oncol 2022;165:376–384.
      1. Westin SN, Lacour RA, Urbauer DL, Luthra R, Bodurka DC, Lu KH, et al. Carcinoma of the lower uterine segment: a newly described association with Lynch syndrome. J Clin Oncol 2008;26:5965–5971.
      1. van den Heerik AS, Horeweg N, Nout RA, Lutgens LC, van der Steen-Banasik EM, Westerveld GH, et al. PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer 2020;30:2002–2007.
    MeSH Terms
    Biopsy*
    Demography
    Endometrial Neoplasms*
    Eosine Yellowish-(YS)
    Exhibition
    Female
    Hematoxylin
    Humans
    Lymph Node Excision*
    Lymphatic Metastasis
    Lymphedema
    Lymphocele
    Neoplasm Metastasis
    Progression-Free Survival*
    Propensity Score
    Recurrence
    Sentinel Lymph Node
    Sentinel Lymph Node Biopsy
    Metrics
    Share
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    Funding Information
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