Laparoscopy guided Indocyanine Green-Guided Pelvic and Para-Aortic Sentinel Lymph Node Mapping in High-Risk Endometrial Cancer: A Step Toward Precision Staging

Laparoscopy guided Indocyanine Green-Guided Pelvic and Para-Aortic Sentinel Lymph Node Mapping in High-Risk Endometrial Cancer: A Step Toward Precision Staging | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Laparoscopy guided Indocyanine Green-Guided Pelvic and Para-Aortic Sentinel Lymph Node Mapping in High-Risk Endometrial Cancer: A Step Toward Precision Staging Dr Aditi Komandur, Dr Rajagopalan Iyer, Dr Subramanyeshwar rao Thammineedi, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8299344/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background: Endometrial cancer is the sixth most common malignancy in women worldwide. While systematic lymphadenectomy provides prognostic information in high-risk cases, it increases perioperative morbidity without a consistent survival benefit. Although sentinel lymph node biopsy (SLNB) has been validated for low-risk disease, its role in intermediate to high-risk endometrial cancer remains uncertain. Objective: To evaluate the diagnostic accuracy of laparoscopic indocyanine green (ICG)-guided SLNB in intermediate-to high-risk endometrial cancer as an alternative to complete lymphadenectomy. Methods: This prospective, non-randomized, single-institute study included 47 women with presumed FIGO stage I–II high-risk endometrial cancer (July 2022–July 2024). National board of examinations India, reviewed the study and approved ethical and scientific clearance – number 2144105624 (30/6/2022) All patients underwent hysterectomy with bilateral salphingo-oophorectomy, laparoscopic ICG-guided pelvic and para aortic SLNB, and complete pelvic and para-aortic lymphadenectomy. ICG was injected into the cervix, and the diagnostic parameters were compared using full lymphadenectomy as the reference. Results: Bilateral mapping was achieved in all cases with reinjection. Pelvic lymph node metastases were found in 6 patients (12.8%), with 5 identified by SLNB (sensitivity 83.3%, negative predictive value 100%). Para-aortic metastases occurred in 5 patients (10.6%), with 4 correctly identified (sensitivity 80%, Negative predictive value 80%). Diagnostic accuracy was 97.87% for pelvic and 88.89% for para-aortic nodes. Mean harvested nodes: 21 pelvic (range 6–34), 33 para-aortic (range 15–58). Nine patients (19.1%) had postoperative complications (mostly Clavien-Dindo grade I–II); readmission rate was 4.2%. Conclusion: ICG-guided SLNB shows high negative predictive value and accuracy in intermediate to high-risk endometrial cancer. It offers a reliable, less invasive alternative to complete lymphadenectomy, potentially reducing surgical morbidity without compromising diagnostic efficacy. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Key messages What is already known on this topic –Indocyanine green (ICG)-guided sentinel lymph node (SLN) mapping is already known to provide high diagnostic accuracy and negative predictive value in high-risk endometrial cancer, though previous studies have largely focused on robotic or open platforms What this study adds –This study demonstrates that laparoscopic bilateral pelvic and para-aortic mapping can be successfully achieved in all patients. It reports pelvic sensitivity of 83.3% and para-aortic sensitivity of 80%, while significantly reducing the extent of lymphadenectomy. The approach lowers surgical morbidity without compromising staging accuracy. How this study might affect research, practice or policy –This study supports the use of laparoscopic Indocyanine green (ICG)-guided sentinel lymph node (SLN) mapping as a feasible, resource-friendly step toward precision staging and minimally invasive management in high-risk endometrial cancer. INTRODUCTION Endometrial cancer is the sixth most common malignancy among women globally, with an estimated 320,000 new cases diagnosed each year(1)(2).By age 75, a woman’s chance of developing endometrial cancer ranges from 0.6% in low-income nations to 1.6% in developed countries. The median age at diagnosis is 61, with approximately 20% of cases occurring before menopause and 5% before the age of 40(3). Histologically, endometrial malignancies are classified into two subgroups: type I and type II. Type I, endometrioid adenocarcinoma, accounts for 90% of cases and is linked to excess estrogen and obesity. These tumours are usually low-grade and have a favourable prognosis. Endometroid carcinomas are further classified into three grades based on differentiation: grade 1 (well differentiated), grade 2 (moderately differentiated) and grade 3 (poorly differentiated)(4) Type II endometrial cancers, include clear-cell, serous papillary subtypes, endometroid grade 3, as well as carcinosarcomas.They carry a worse prognosis and are classified as high-grade tumours.(5). Endometrial malignancies can be categorized as high-risk (high grade or stage IB or beyond) or low risk (low grade or stage IA). Factors influencing prognosis and survival include disease stage at diagnosis, histological grade, depth of myometrial invasion, lymph vascular invasion and lymph node status. Notably, grade 3 histology, greater than 50% depth of myometrial invasion are associated with poor survival and high rates of pelvic and para-aortic lymph node metastases(6) The mean 5-year survival rates are 85% for stage I, 70% for stage II, 50% for stage III, and 18% for stage IV (7) Endometrial carcinoma follows two consistent lymphatic pathways irrespective of injection site: A) Upper paracervical pathway (UPP) running along the uterine artery and Draining into medial external and/or obturator lymph nodes before crossing the external iliac artery with a continued course lateral to the common iliac artery to the lateral precaval and paraaortic areas. B) Lower paracervical pathway (LPP) courses along the upper rim of the sacrouterine ligament to the presacral area medial of the internal iliac artery. The internal iliac and/or presacral lymphatic channels continue medial to the common iliac artery to the medial paraaortic and precaval areas. The right and the left lymphatic vessels communicate just cranial to the promontory. The Infundibulo-pelvic pathway (IPP) courses along the fallopian tube and upper broad ligament via the Infundibulo-pelvic ligament to its origin. While classic surgical staging for high-risk endometrial cancer includes pelvic and para-aortic lymphadenectomy, systematic lymphadenectomy has not consistently demonstrated improved overall or disease-free survival. (8)(9) Prior to the mid-1980s, systematic retroperitoneal lymph node dissection (LND) was not performed in endometrial cancer. GOG 33 in 1987 identified the increased risk of pelvic lymph node metastasis in more deeply invasive and higher-grade endometrial cancers (8). In a study by Sucheta et al., lymph node involvement was found in 24.3% of patients with over 50% myometrial invasion, compared to 5.8% in those with disease limited to the inner half of myometrium(P = 0.001). Metastasis to pelvic and para-aortic nodes was noted in 4% of patients, while isolated para-aortic nodes were found in 4% of intermediate-high-risk cases (10) The FIRES trial(11) and SENTI ENDO trial(12) proved beyond doubt the role of sentinel lymph node biopsy in the context of low-risk Endometrial cancer. However, its role in high-risk Endometrial cancer remains unclear. In 2019 Jan Persson et al. published a study to prospectively assess the diagnostic accuracy of a pelvic sentinel lymph node (SLN) algorithm in high-risk endometrial cancer (HREC). The described pelvic sentinel lymph node algorithm was found to safely replace a full lymphadenectomy in high-risk endometrial cancer(13) Given the high morbidity associated with complete pelvic and para-aortic nodal dissection and the low incidence of para-aortic nodal metastasis, we undertook a validation study of indocyanine green (ICG) guided sentinel node biopsy in intermediate to high-risk endometrial cancer. While the SHREC trial has validated that sentinel lymph node biopsy alone is sufficient for high risk endometrial cancer – all surgeries in this study were performed on a robotic platform . In India where robotic platforms are seldom accessible to the majority of patients laparoscopy and open surgeries prevail . Our study not only validates the sentinel node algorithm in high risk endometrial cancer but also confirms the feasibility in laparoscopic surgeries. Materials and methods In accordance with the journal’s guidelines, we will provide our data for independent analysis by a selected team by the Editorial Team for the purposes of additional data analysis or for the reproducibility of this study in other centers if such is requested. National board of examinations India, reviewed the study and approved ethical and scientific clearance – number 2144105624 A written informed consent was obtained from all subjects or a legal surrogate Aim -To prospectively assess the diagnostic accuracy of sentinel lymph node algorithm in selective intermediate to high risk endometrial cancers. Objectives – To assess sensitivity, specificity, false negative rates, positive and negative predictive values of sentinel node biopsy in comparison with systematic lymph node dissection in high risk endometrial carcinoma This study is a prospective non-randomized single institute study. Consecutive women, with presumed International Federation of Obstetrics and Gynecology stage I-II high risk endometrial cancer, were assessed for eligibility from 1/07/2022 to 30/07/2024. The extent of myometrial and/or cervical invasion as well as presence of locally advanced disease was evaluated by MRI. All patients underwent a preoperative computed tomography scan of the thorax and abdomen or PET scan of the whole body. Preoperative histological diagnosis and grade was decided on specimen obtained from endometrial biopsy, hysteroscopy or curettage. Written informed consent was obtained from all enrolled women. The study was approved by the respective ethical committee. The study was conducted at a single center with 25- year prior experience in laparoscopic surgery and an annual caseload of 250-300 Endometrial cancer procedures. Enrolled women were scheduled for laparoscopic/open hysterectomy, bilateral salpingo-oophorectomy, pelvic with para aortic Sentinel lymph node biopsy along with Pelvic lymph node dissection and Infra renal para aortic lymph node dissection. The Sentinel lymph node procedure was performed according to a defined anatomically based surgical algorithm. A 2.5 mg/ml sterile water solution of Indocyanine green was prepared. A 23G spinal needle was used to slowly inject 0.5 ml into the cervix at 3 o clock and 9 o clock position, respectively. Half the volume was injected submucosally, and the remaining half injected one centimeter into the cervical stroma. The Near Infrared mode was utilized for identification of the upper paracervical pathway (UPP) and lower paracervical pathways (LPP). If a pathway was not visualized through the peritoneum, the avascular presacral, paravesical and pararectal planes were opened, keeping the lymphatic channels intact. In case of non-display in any pathway after 10 min, an ipsilateral reinjection of the Indocyanine green solution was performed. All Indocyanine green positive nodes were considered as sentinel lymph nodes. Indocyanine green afferent pathways leading to nodes with no uptake were also considered as sentinel nodes. Nodes macroscopically suspicious metastatic were also harvested as a part of Sentinel lymph node biopsy algorithm , regardless of Indocyanine green uptake .The positions and types of Sentinel lymph nodes were drawn on an anatomical chart. After removal of Sentinel lymph nodes, a Pelvic lymph node dissection and Infrarenal para aortic lymph node dissection were performed. The pathologists were not blinded to the results of Sentinel lymph nodes and non-sentinel lymph nodes when performing their assessment. INCLUSION CRITERIA: - Age 18 years and older at the time of informed consent - A pathologically proven endometrial carcinoma of any histologic subtype, clinically stage I-II planned for primary surgery. - At least one of the following preoperative high-risk criteria (endometrioid cancer FIGO grade III, a non-endometrioid histology, >/= 50% myometrial tumor invasion or cervical stromal invasion) - Ability to understand and sign an informed consent. EXCLUSION CRITERIA: -Non-consenting patients. - Pregnancy - Inability to understand written and/or oral study information. - WHO performance status III or more. - Age > 85 years and WHO performance status II or more. - Preexisting lower limb lymphoedema grade II or more. - Locally advanced disease or intra-abdominal/distant metastases at preoperative CT, MRI or ultrasonography. Statistical analysis The analysis of sensitivity, specificity and accuracy was evaluated per patient with regard to the Sentinel lymph node algorithms. A full Pelvic and para-aortic lymph node dissection was performed after the removal of Sentinel lymph nodes. Each woman served as her own control. Results A total of 47 women were enrolled and included in the final analysis. Demographic and clinical data are presented in Table 1. The Indocanine green sentinel lymph node algorithm had a sensitivity of 83.3% and a negative predictive value of 97.6% for the detection of pelvic nodes. For the detection of para aortic nodes the algorithm had a sensitivity of 80% and a negative predictive value of 80% . After reinjection, the bilateral mapping rate was 100% . All 47 women underwent pelvic and para aortic Sentinel lymph node mapping along with a pelvic lymph node dissection and an Infra renal para aortic lymph node dissection. The mean number of pelvic and para-aortic nodes was 21 (range 6-34) and 33 (15-58) , respectively. The location of Sentinel lymph nodes is shown in Fig. 5. Six women had pelvic Lymph node metastases, and 5 of those were correctly identified by the Sentinel lymph node indocyanine green algorithm. In one women apart from the indocyanine green avid node s , a non indocyanine green avid lymph node was also positive in the pelvic basin. Five out of these six women had para-aortic Lymph node metastases. Only 1 woman (2.1%) had isolated para aortic metastasis. Five women had para aortic Lymph node metastases , and 4 of those were correctly identified by the Sentinel lymph node indocyanine green algorithm. In one women, apart from the Sentinel lymph node biopsy , non sentinel lymph node biopsy nodes were also positive. Only one woman had a false negative para aortic sentinel lymph node biopsy similar to the results that we found in the pelvic basin. According to the final histology, erroneous risk group allocation occurred in 9% women, mainly due to preoperative overestimation of myometrial depth invasion in women with endometrioid histology. In only one women, a conversion to laparotomy was necessary due to an intraoperative complication. No adverse events occurred during injection of Indocyanine green or during the Sentinel lymph node biopsy procedure per se. 9(19.1%) women had a postoperative complication within 30 days after surgery of which more than 85% were Clavien Dindo Grade I or II . The readmission rate following surgery was 4.2%. Diagnostic Accuracy : Pelvic Nodes : The Indocyanine green algorithm had a diagnostic accuracy of 97.87%. The 100% specificity highlights that once the Sentinel lymph node is identified as negative, it is quite reliable. Para-aortic Nodes : The algorithm’s sensitivity of 80% for para-aortic nodes is not very effective, indicating that there is room for improvement. A specificity of 100% further supports the reliability of the algorithm in ruling out disease when the Sentinel lymph node is negative. The study's findings reveal that the Sentinel lymph node Indocyanine green algorithm was able to identify all pelvic lymph node metastases correctly, except in one case where non- Indocyanine green -avid nodes were also positive. This highlights a limitation in which the Sentinel lymph node algorithm may not detect all positive nodes, particularly in the presence of non- Indocyanine green -avid metastases. The relatively low rate of complications (19.1%) and absence of adverse events during Indocyanine green injection or Sentinel lymph node procedure suggest that the Sentinel lymph node technique is generally safe. Conversion to laparotomy and the occurrence of a grade V complication, although concerning, are not indicative of a systemic issue with the Sentinel lymph node method itself but rather specific to individual cases. Table 1 -Summary of demographics Age(years)- mean 62.1 Body mass index(kg/m2) – mean 30.3 ECOG performance score 0 3(6.4%) 1 40(85.1%) 2 4(8.5%) ASA – class I 19.10% II 80.90% Post operative histology Endometroid adenocarcinoma Grade I-II 25 Endometroid adenocarcinoma Grade III 10 Serous adenocarcinoma 5 Clear cell carcinoma 6 Other 1 Stage FIGO 2009 IA 9 IB 20 II 8 IIIA-B 10 Operative time (skin to skin) minutes 284 Estimated blood loss (ml) 249 Discussion Endometrial cancer is one of the most prevalent gynecological malignancies, and lymph node involvement is a critical prognostic factor. Accurate nodal assessment not only influences prognosis but also guides decisions regarding adjuvant therapy. Magnetic resonance imaging (MRI), owing to its superior soft tissue contrast and multiplanar capabilities, is widely regarded as the most reliable modality for the preoperative assessment and staging of endometrial carcinoma. Combined with preoperative histopathology, MRI facilitates individualized treatment planning for patients. Summary of results -In this prospective study, we analyzed 47 patients with intermediate-to high-risk endometrial carcinoma treated between July 2022 and July 2024. All patients underwent contrast-enhanced MRI or PET-CT and were staged according to the 2009 International Federation of Gynecology and Obstetrics classification. Risk categorization followed the ESTRO/ESGO guidelines, and only patients meeting the criteria for intermediate-high or high-risk disease were included. Surgical management involved hysterectomy with bilateral salpingo-oophorectomy, indocyanine green (ICG)-guided pelvic and para-aortic sentinel lymph node biopsy (SLNB), followed by completion template pelvic and para-aortic lymphadenectomy. Comprehensive pelvic and para-aortic lymphadenectomy is associated with significant morbidity, including pelvic lymphoceles and lower-limb lymphedema. Moreover, when lymph node metastases are detected, adjuvant therapy, often radiation with or without chemotherapy, is usually indicated, compounding the patient burden. Given that lymphadenectomy serves a primarily prognostic rather than therapeutic role, less invasive alternatives, such as sentinel lymph node biopsy, warrant evaluation, particularly in high-risk populations. While the role of indocyanine green -guided sentinel lymph node biopsy is well established in low-risk endometrial cancer, data supporting its utility in high-risk diseases remain limited. In our study, indocyanine green -guided sentinel lymph node biopsy demonstrated an accuracy of over 90% in detecting both the pelvic and para-aortic lymph nodes. Specifically, we found a sensitivity of 83.3% and a negative predictive value (NPV) of 97.6% for pelvic nodes and a sensitivity and negative predictive value of 80% for para-aortic nodes. Results in context of published literature- These findings are partially comparable to those of the SHREC trial by Persson et al., in which the indocyanine green -guided sentinel lymph node algorithm demonstrated a sensitivity of 98% and Negative predictive value of 99.5%. Their cohort included 257 women who underwent pelvic sentinel lymph node mapping and pelvic lymphadenectomy, of whom 81% also underwent infrarenal para-aortic lymphadenectomy (IRPALND). Although our sensitivity values were slightly lower, the comparable Negative predictive value suggests reliability in ruling out nodal metastases. The difference in sensitivity may be attributable to the smaller sample size; a larger cohort might yield improved results. Similarly, the SENTOR trial enrolled 156 patients with intermediate- and high-grade endometrial cancer and reported a lymph node positivity rate of 17.3%, closely mirroring our rate of 14.8%. The median number of pelvic lymph nodes harvested in our study was comparable to that in SENTOR, whereas the yield of para-aortic nodes in our cohort exceeded that reported in most published trials. Despite the extensive lymphadenectomy performed in our study, the incidence of significant postoperative complications was low. This raises the possibility that omitting full template dissections, especially in favor of sentinel lymph node biopsy, could further reduce morbidity without compromising the diagnostic accuracy. Togami et al. assessed the risk factors for lymphatic complications following lymphadenectomy for endometrial cancer and reported a 14.9% incidence of lower extremity edema and an 11.4% incidence of pelvic lymphoceles. Notably, circumflex iliac node (CIN) removal and the surgical approach were identified as independent risk factors. In our study, pelvic lymphoceles were detected in nine out of 47 patients (19.1%), most of whom were asymptomatic and identified on follow-up ultrasound. Lower extremity edema occurred in 6 patients (12.7%) at a median follow-up of 6 months. However, we were unable to assess the long-term incidence of lymphedema due to the limited duration of follow-up. Strenghts and Limitations of the Study This study is a prospective institute based study. All procedures were performed by highly experienced surgeons to ensure quality of surgery. Previous studies have showed results similar to ours on robotic or open platforms whereas our study is the first study to show feasibility on laparoscopic platform. In resource limited settings where robotic surgery is unavailable, laparoscopy serves as a good alternative while maintaining the quality of surgical outcomes This study had several limitations. The most significant limitation is the small sample size, which may limit the generalizability of the findings. Additionally, the absence of ultrastaging in sentinel lymph node biopsy (SLNB) represents a critical drawback, potentially affecting the accuracy of the nodal assessment. The study was conducted at a single center, and although the surgical procedures were standardized and consistently performed, 97% were performed via laparoscopy, a technique that requires a steep learning curve, particularly for complex procedures. Furthermore, the relatively short follow-up period precluded the evaluation of long-term complications and recurrence rates. Implications of practice and future research- Sentinel lymph node biopsy is expected to replace lymph node dissection in high risk endometrial cancer. These procedures will increasingly be performed using minimally invasive techniques. The future may see a paradigm shift towards tailoring surgery based on tumour’s molecular profile. Conclusion The sentinel lymph node (SLN) algorithm is a promising less invasive alternative to systematic pelvic lymphadenectomy. It offers the potential for the accurate detection of lymph node metastases while reducing surgical morbidity. However, larger multicenter studies with longer follow-up and incorporation of ultrastaging are needed to validate these findings and fully establish the clinical utility of the sentinel lymph node approach. ​​ Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki and its later amendments. Approval was obtained from the Institutional Ethics Committee, and written informed consent was obtained from all participants. National board of examinations in medical sciences , medical enclave, Ansari nagar, new delhi India, reviewed the study and approved ethical and scientific clearance – number 2144105624 Date of registration -30/6/2022 Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This study received no external funding. Authors’ contributions AK conceived and designed the study. AK and PA collected the data. RI and ZU performed the data analysis. FZ and AK did the statistical work . AK,SR,RS and ASS drafted the manuscript. All authors critically revised the manuscript and approved the final version. Acknowledgements The authors would like to thank the patients who participated in this study and the clinical staff involved in their care. References Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JWW, Comber H, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer. 2013 Apr;49(6):1374–403. Shylasree TS, Bajpai J. 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Risk factors for lymphatic complications following lymphadenectomy in patients with endometrial cancer. Taiwan J Obstet Gynecol. 2020 May 1;59(3):420–4. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 17 Feb, 2026 Reviewers agreed at journal 04 Feb, 2026 Reviews received at journal 29 Jan, 2026 Reviewers agreed at journal 20 Jan, 2026 Reviewers invited by journal 20 Jan, 2026 Editor assigned by journal 19 Jan, 2026 Editor invited by journal 26 Dec, 2025 Submission checks completed at journal 26 Dec, 2025 First submitted to journal 26 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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1","display":"","copyAsset":false,"role":"figure","size":290003,"visible":true,"origin":"","legend":"\u003cp\u003eDissection of paracaval node. The Indocyanine green avid lymphatic channels are draining into the lymph node\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8299344/v1/9e84cf695f72f2d5d1b6858d.png"},{"id":100865785,"identity":"b2d86c03-e699-423f-8bc1-4082fd32eb7b","added_by":"auto","created_at":"2026-01-22 08:27:33","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":250924,"visible":true,"origin":"","legend":"\u003cp\u003eExternal iliac lymphatic channels from the Lower para cervical pathway draining into a node\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8299344/v1/3556f94363daabc5fb7a68eb.png"},{"id":100865910,"identity":"0cba05eb-a4ae-45d5-8451-ebc4fb8e72ab","added_by":"auto","created_at":"2026-01-22 08:27:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":328571,"visible":true,"origin":"","legend":"\u003cp\u003eObturator group of lymph nodes with the corresponding lymphatic channels\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8299344/v1/8990f9c89ef999b663304fb1.png"},{"id":100865696,"identity":"1166dd7c-9b8d-44be-9f67-15ae04879c7b","added_by":"auto","created_at":"2026-01-22 08:27:21","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":337895,"visible":true,"origin":"","legend":"\u003cp\u003eAfter a complete B/L pelvic lymph node dissection and hysterectomy with B/L salphingo-oopherectomy\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8299344/v1/f6045d6ce9809474e510f266.png"},{"id":100865698,"identity":"0ad33712-7dac-4e4a-a6a9-d853a8773517","added_by":"auto","created_at":"2026-01-22 08:27:22","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":351321,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution and typical localization of pelvic sentinel nodes defined by indocyanine green (ICG) and proportion of metastatic sentinel nodes per pelvic lymphatic compartment/uterine lymphatic pathway in high-risk endometrial cancer\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8299344/v1/aaeb9f8efc9364f2be711f0c.png"},{"id":102298526,"identity":"abd82c97-872b-4b30-b6a7-cbc0f44076da","added_by":"auto","created_at":"2026-02-10 10:43:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2912081,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8299344/v1/70e2867e-0789-4c10-8cb7-4fc1e2ad33d5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Laparoscopy guided Indocyanine Green-Guided Pelvic and Para-Aortic Sentinel Lymph Node Mapping in High-Risk Endometrial Cancer: A Step Toward Precision Staging","fulltext":[{"header":"Key messages","content":"\u003cp\u003eWhat is already known on this topic –Indocyanine green (ICG)-guided sentinel lymph node (SLN) mapping is already known to provide high diagnostic accuracy and negative predictive value in high-risk endometrial cancer, though previous studies have largely focused on robotic or open platforms\u003c/p\u003e\n\u003cp\u003eWhat this study adds –This study demonstrates that laparoscopic bilateral pelvic and para-aortic mapping can be successfully achieved in all patients. It reports pelvic sensitivity of 83.3% and para-aortic sensitivity of 80%, while significantly reducing the extent of lymphadenectomy. The approach lowers surgical morbidity without compromising staging accuracy.\u003c/p\u003e\n\u003cp\u003eHow this study might affect research, practice or policy –This study \u0026nbsp;supports the use of laparoscopic Indocyanine green (ICG)-guided sentinel lymph node (SLN) mapping as a feasible, resource-friendly step toward precision staging and minimally invasive management in high-risk endometrial cancer.\u003c/p\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eEndometrial cancer is the sixth most common malignancy among women globally, with an estimated 320,000 new cases diagnosed each year(1)(2).By age 75, a woman\u0026rsquo;s chance of developing endometrial cancer ranges from 0.6% in low-income nations to 1.6% in developed countries. The median age at diagnosis is 61, with approximately 20% of cases occurring before menopause and 5% before the age of 40(3).\u003c/p\u003e\n\u003cp\u003eHistologically, endometrial malignancies are classified into two subgroups: type I and type II. Type I, \u0026nbsp;endometrioid adenocarcinoma, accounts for 90% of cases and is linked to excess estrogen and obesity. These tumours are usually low-grade and \u0026nbsp;have a favourable prognosis. Endometroid carcinomas are further classified into three grades based on differentiation: grade 1 (well differentiated), grade 2 (moderately differentiated) and grade 3 (poorly differentiated)(4)\u003c/p\u003e\n\u003cp\u003eType II endometrial cancers, \u0026nbsp;include clear-cell, serous papillary subtypes, endometroid grade 3, as well as carcinosarcomas.They carry a worse prognosis and are classified as high-grade tumours.(5).\u0026nbsp;Endometrial malignancies can be categorized as high-risk (high grade or stage IB or beyond) or low risk (low grade or stage IA).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Factors influencing prognosis and survival include disease stage at diagnosis, histological grade, depth of myometrial invasion, lymph vascular invasion and lymph node status. Notably, grade 3 histology, greater than 50% depth of myometrial invasion are associated with poor survival and high rates of pelvic and para-aortic lymph node metastases(6) \u0026nbsp;The mean 5-year survival rates are 85% for stage I, 70% for stage II, 50% for stage III, and 18% for stage IV\u0026nbsp;(7)\u003c/p\u003e\n\u003cp\u003eEndometrial carcinoma follows\u0026nbsp;two consistent lymphatic pathways irrespective of injection site:\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;A) Upper paracervical pathway (UPP) running along the uterine artery and\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Draining into medial external and/or obturator lymph nodes before crossing the external iliac artery with a continued course lateral to the common iliac artery to the lateral precaval and paraaortic areas. B) Lower paracervical pathway (LPP) courses along the upper rim of the sacrouterine ligament to the presacral area medial of the internal iliac artery. The internal iliac and/or presacral lymphatic channels continue medial to the common iliac artery to the medial paraaortic and precaval areas.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe right and the left lymphatic vessels communicate just cranial to the promontory.\u003c/p\u003e\n\u003cp\u003eThe Infundibulo-pelvic pathway (IPP) courses along the fallopian tube and upper broad ligament via the Infundibulo-pelvic ligament to its origin.\u003c/p\u003e\n\u003cp\u003eWhile classic surgical staging for high-risk endometrial cancer includes pelvic and para-aortic lymphadenectomy, systematic lymphadenectomy has not consistently demonstrated improved overall or disease-free survival.\u0026nbsp;(8)(9)\u003c/p\u003e\n\u003cp\u003ePrior to the mid-1980s, systematic retroperitoneal lymph node dissection (LND) was not performed in endometrial cancer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGOG 33 in 1987 identified the increased risk of pelvic lymph node metastasis in more deeply invasive and higher-grade endometrial cancers\u0026nbsp;(8).\u003c/p\u003e\n\u003cp\u003eIn a study by Sucheta et al., lymph node involvement was found in 24.3% of patients with over 50% myometrial invasion, compared to 5.8% in those with disease limited to the inner half of myometrium(P = 0.001). Metastasis to pelvic and para-aortic nodes was noted in 4% of patients, while isolated para-aortic nodes were found in 4% of intermediate-high-risk cases\u0026nbsp;(10)\u003c/p\u003e\n\u003cp\u003eThe FIRES trial(11) and SENTI ENDO trial(12) proved beyond doubt the role of sentinel lymph node biopsy in the context of low-risk Endometrial cancer. However, its role in high-risk Endometrial cancer remains unclear.\u003c/p\u003e\n\u003cp\u003eIn 2019 Jan Persson et al. published a study to prospectively assess the diagnostic accuracy of a pelvic sentinel lymph node (SLN) algorithm in high-risk endometrial cancer (HREC).\u0026nbsp;The described pelvic sentinel lymph node \u0026nbsp;algorithm was found to safely replace a full lymphadenectomy in high-risk endometrial cancer(13)\u003c/p\u003e\n\u003cp\u003eGiven the high morbidity associated with complete pelvic and para-aortic nodal dissection and the low incidence of para-aortic nodal metastasis, we undertook a validation study of indocyanine green (ICG) guided sentinel node biopsy in intermediate to high-risk endometrial cancer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhile \u0026nbsp;the SHREC trial has \u0026nbsp;validated that sentinel lymph node \u0026nbsp; biopsy alone is sufficient \u0026nbsp;for high risk endometrial cancer \u0026ndash; all surgeries in this study were performed on a robotic platform . In India where robotic platforms are seldom accessible to the majority of patients laparoscopy and open surgeries prevail . Our study not only validates the sentinel node algorithm in high risk endometrial cancer but also confirms the feasibility in laparoscopic surgeries.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eIn accordance with the journal\u0026rsquo;s guidelines, we will provide our data for independent analysis by a selected team by the Editorial Team for the purposes of additional data analysis or for the reproducibility of this study in other centers if such is requested.\u003c/p\u003e\n\u003cp\u003eNational board of examinations India, reviewed the study and approved ethical and scientific clearance \u0026ndash; number 2144105624\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA written informed consent was obtained from all subjects or a legal surrogate\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAim\u0026nbsp;\u003c/strong\u003e-To prospectively assess the diagnostic accuracy of sentinel lymph node algorithm in selective intermediate to high risk endometrial cancers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives\u0026nbsp;\u003c/strong\u003e\u0026ndash; To\u0026nbsp;assess sensitivity, specificity, false negative rates, positive and negative predictive values of sentinel node biopsy in comparison with systematic lymph node dissection in high risk endometrial carcinoma\u003c/p\u003e\n\u003cp\u003eThis study is a prospective non-randomized single institute study. Consecutive women, with presumed International Federation of Obstetrics and Gynecology stage I-II high risk endometrial cancer, were assessed for eligibility from\u0026nbsp;1/07/2022 to 30/07/2024. The extent of myometrial and/or cervical invasion as well as presence of locally advanced disease was evaluated by MRI. All patients underwent a preoperative computed tomography scan of the thorax and abdomen or PET scan of the whole body. Preoperative histological diagnosis and grade was decided on specimen obtained from endometrial biopsy, hysteroscopy or curettage. Written informed consent was obtained from all enrolled women. The study was approved by the respective ethical committee. The study was conducted at a single center with 25- year prior experience in laparoscopic surgery and an annual caseload of 250-300 Endometrial cancer procedures. Enrolled women were scheduled for laparoscopic/open hysterectomy, bilateral salpingo-oophorectomy, pelvic with para aortic Sentinel lymph node biopsy along with Pelvic lymph node dissection and Infra renal para aortic lymph node dissection.\u003c/p\u003e\n\u003cp\u003eThe Sentinel lymph node procedure was performed according to a defined anatomically based surgical algorithm. A 2.5 mg/ml sterile water solution of Indocyanine green was prepared. A 23G spinal needle was used to slowly inject 0.5 ml into the cervix at 3 o clock and 9 o clock position, respectively. Half the volume was injected submucosally, and the remaining half injected one centimeter into the cervical stroma. The Near Infrared mode was utilized for identification of the upper paracervical pathway (UPP) and lower paracervical pathways (LPP). If a pathway was not visualized through the peritoneum, the avascular presacral, paravesical and pararectal planes were opened, keeping the lymphatic channels intact. In case of non-display in any pathway after 10 min, an ipsilateral reinjection of the Indocyanine green solution was performed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll Indocyanine green positive nodes were considered as sentinel lymph nodes. Indocyanine green afferent pathways leading to nodes with no uptake were also considered as sentinel nodes. Nodes macroscopically suspicious metastatic were also harvested as a part of Sentinel lymph node biopsy algorithm , regardless of Indocyanine green uptake .The positions and types of Sentinel lymph nodes were drawn on an anatomical chart. After removal of Sentinel lymph nodes, a Pelvic lymph node dissection and Infrarenal para aortic lymph node dissection were performed. The pathologists were not blinded to the results of Sentinel lymph nodes and non-sentinel lymph nodes when performing their assessment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eINCLUSION CRITERIA:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e- Age 18 years and older at the time of informed consent\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;- A pathologically proven endometrial carcinoma of any histologic subtype, clinically stage I-II planned for primary surgery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e- At least one of the following preoperative high-risk criteria (endometrioid cancer FIGO grade III, a non-endometrioid histology, \u0026gt;/= 50% myometrial tumor invasion or cervical stromal invasion)\u003c/p\u003e\n\u003cp\u003e- Ability to understand and sign an informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEXCLUSION CRITERIA:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e-Non-consenting patients.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;- Pregnancy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e- Inability to understand written and/or oral study information.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;- WHO performance status III or more.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e- Age \u0026gt; 85 years and WHO performance status II or more.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;- Preexisting lower limb lymphoedema grade II or more.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;- Locally advanced disease or intra-abdominal/distant metastases at preoperative CT, MRI or ultrasonography.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe analysis of sensitivity, specificity and accuracy was evaluated per patient with regard to the Sentinel lymph node algorithms. A full Pelvic and para-aortic lymph node dissection was performed after the removal of Sentinel lymph nodes. Each woman served as her own control.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 47 women were enrolled and included in the final analysis. Demographic and clinical data are presented in Table 1. The Indocanine green sentinel lymph node algorithm had a sensitivity of 83.3% and a negative predictive value of 97.6% for the detection of pelvic nodes. For the detection of para aortic nodes the algorithm had a sensitivity of 80% and a negative predictive value of 80% . After reinjection, the bilateral mapping rate was 100% . All 47 women underwent pelvic and para aortic Sentinel lymph node mapping along with a \u0026nbsp;pelvic lymph node dissection and an Infra renal para aortic lymph node dissection. The mean number of pelvic and para-aortic nodes was 21 (range 6-34) and 33 (15-58) , respectively. The location of Sentinel lymph nodes is shown in Fig. 5.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Six women had pelvic Lymph node metastases, and 5 of those were correctly identified by the Sentinel lymph node indocyanine green algorithm. In one women apart from the indocyanine green avid node\u003cstrong\u003es\u003c/strong\u003e, a non indocyanine green avid lymph node was also positive in the pelvic basin. Five out of these six women had para-aortic Lymph node metastases. Only 1 woman (2.1%) had isolated para aortic metastasis.\u003c/p\u003e\n\u003cp\u003eFive women had para aortic Lymph node metastases , and 4 of those were correctly identified by the Sentinel lymph node indocyanine green algorithm. In one women, apart from the Sentinel lymph node biopsy , non sentinel lymph node biopsy nodes were also positive. Only one woman had a false negative para aortic sentinel lymph node biopsy similar to the results that we found in the pelvic basin.\u003c/p\u003e\n\u003cp\u003eAccording to the final histology, erroneous risk group allocation occurred in 9% women, mainly due to preoperative overestimation of myometrial depth invasion in women with endometrioid histology.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn only one women, a conversion to laparotomy was necessary due to an intraoperative complication. No adverse events occurred during injection of Indocyanine green or during the Sentinel lymph node biopsy procedure per se.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e9(19.1%) women had a postoperative complication within 30 days after surgery of which more than 85% were Clavien Dindo Grade I or II . \u0026nbsp;The readmission rate following surgery was 4.2%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic Accuracy\u003c/strong\u003e:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003ePelvic Nodes\u003c/strong\u003e: The Indocyanine green algorithm had a diagnostic accuracy of 97.87%. The 100% specificity highlights that once the Sentinel lymph node is identified as negative, it is quite reliable.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePara-aortic Nodes\u003c/strong\u003e: The algorithm\u0026rsquo;s sensitivity of 80% for para-aortic nodes is not very effective, indicating that there is room for improvement. A specificity of 100% further supports the reliability of the algorithm in ruling out disease when the Sentinel lymph node is negative.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe study\u0026apos;s findings reveal that the Sentinel lymph node Indocyanine green algorithm was able to identify all pelvic lymph node metastases correctly, except in one case where non- Indocyanine green -avid nodes were also positive. This highlights a limitation in which the Sentinel lymph node algorithm may not detect all positive nodes, particularly in the presence of non- Indocyanine green -avid metastases.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe relatively low rate of complications (19.1%) and absence of adverse events during Indocyanine green injection or Sentinel lymph node procedure suggest that the Sentinel lymph node technique is generally safe. Conversion to laparotomy and the occurrence of a grade V complication, although concerning, are not indicative of a systemic issue with the Sentinel lymph node method itself but rather specific to individual cases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 -Summary of demographics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"485\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eAge(years)- mean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e62.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eBody mass index(kg/m2) \u0026ndash; mean\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e30.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eECOG performance score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3(6.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e40(85.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e4(8.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eASA \u0026ndash; class\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eI\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e19.10%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e80.90%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ePost operative histology\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eEndometroid adenocarcinoma\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eGrade I-II\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eEndometroid adenocarcinoma Grade III\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSerous adenocarcinoma\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eClear cell carcinoma\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eOther\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eStage FIGO 2009\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eIB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eIIIA-B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eOperative time (skin to skin) minutes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e284\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eEstimated blood loss (ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e249\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eEndometrial cancer is one of the most prevalent gynecological malignancies, and lymph node involvement is a critical prognostic factor. Accurate nodal assessment not only influences prognosis but also guides decisions regarding adjuvant therapy. Magnetic resonance imaging (MRI), owing to its superior soft tissue contrast and multiplanar capabilities, is widely regarded as the most reliable modality for the preoperative assessment and staging of endometrial carcinoma. Combined with preoperative histopathology, MRI facilitates individualized treatment planning for patients.\u003c/p\u003e \u003cp\u003e\u003cb\u003eSummary of results\u003c/b\u003e-In this prospective study, we analyzed 47 patients with intermediate-to high-risk endometrial carcinoma treated between July 2022 and July 2024. All patients underwent contrast-enhanced MRI or PET-CT and were staged according to the 2009 International Federation of Gynecology and Obstetrics classification. Risk categorization followed the ESTRO/ESGO guidelines, and only patients meeting the criteria for intermediate-high or high-risk disease were included. Surgical management involved hysterectomy with bilateral salpingo-oophorectomy, indocyanine green (ICG)-guided pelvic and para-aortic sentinel lymph node biopsy (SLNB), followed by completion template pelvic and para-aortic lymphadenectomy.\u003c/p\u003e \u003cp\u003eComprehensive pelvic and para-aortic lymphadenectomy is associated with significant morbidity, including pelvic lymphoceles and lower-limb lymphedema. Moreover, when lymph node metastases are detected, adjuvant therapy, often radiation with or without chemotherapy, is usually indicated, compounding the patient burden. Given that lymphadenectomy serves a primarily prognostic rather than therapeutic role, less invasive alternatives, such as sentinel lymph node biopsy, warrant evaluation, particularly in high-risk populations.\u003c/p\u003e \u003cp\u003eWhile the role of indocyanine green -guided sentinel lymph node biopsy is well established in low-risk endometrial cancer, data supporting its utility in high-risk diseases remain limited. In our study, indocyanine green -guided sentinel lymph node biopsy demonstrated an accuracy of over 90% in detecting both the pelvic and para-aortic lymph nodes. Specifically, we found a sensitivity of 83.3% and a negative predictive value (NPV) of 97.6% for pelvic nodes and a sensitivity and negative predictive value of 80% for para-aortic nodes.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults in context of published literature-\u003c/b\u003eThese findings are partially comparable to those of the SHREC trial by Persson et al., in which the indocyanine green -guided sentinel lymph node algorithm demonstrated a sensitivity of 98% and Negative predictive value of 99.5%. Their cohort included 257 women who underwent pelvic sentinel lymph node mapping and pelvic lymphadenectomy, of whom 81% also underwent infrarenal para-aortic lymphadenectomy (IRPALND). Although our sensitivity values were slightly lower, the comparable Negative predictive value suggests reliability in ruling out nodal metastases. The difference in sensitivity may be attributable to the smaller sample size; a larger cohort might yield improved results.\u003c/p\u003e \u003cp\u003eSimilarly, the SENTOR trial enrolled 156 patients with intermediate- and high-grade endometrial cancer and reported a lymph node positivity rate of 17.3%, closely mirroring our rate of 14.8%. The median number of pelvic lymph nodes harvested in our study was comparable to that in SENTOR, whereas the yield of para-aortic nodes in our cohort exceeded that reported in most published trials.\u003c/p\u003e \u003cp\u003eDespite the extensive lymphadenectomy performed in our study, the incidence of significant postoperative complications was low. This raises the possibility that omitting full template dissections, especially in favor of sentinel lymph node biopsy, could further reduce morbidity without compromising the diagnostic accuracy.\u003c/p\u003e \u003cp\u003eTogami et al. assessed the risk factors for lymphatic complications following lymphadenectomy for endometrial cancer and reported a 14.9% incidence of lower extremity edema and an 11.4% incidence of pelvic lymphoceles. Notably, circumflex iliac node (CIN) removal and the surgical approach were identified as independent risk factors. In our study, pelvic lymphoceles were detected in nine out of 47 patients (19.1%), most of whom were asymptomatic and identified on follow-up ultrasound. Lower extremity edema occurred in 6 patients (12.7%) at a median follow-up of 6 months. However, we were unable to assess the long-term incidence of lymphedema due to the limited duration of follow-up.\u003c/p\u003e\n\u003ch3\u003eStrenghts and Limitations of the Study\u003c/h3\u003e\n\u003cp\u003eThis study is a prospective institute based study. All procedures were performed by highly experienced surgeons to ensure quality of surgery. Previous studies have showed results similar to ours on robotic or open platforms whereas our study is the first study to show feasibility on laparoscopic platform. In resource limited settings where robotic surgery is unavailable, laparoscopy serves as a good alternative while maintaining the quality of surgical outcomes\u003c/p\u003e \u003cp\u003eThis study had several limitations. The most significant limitation is the small sample size, which may limit the generalizability of the findings. Additionally, the absence of ultrastaging in sentinel lymph node biopsy (SLNB) represents a critical drawback, potentially affecting the accuracy of the nodal assessment. The study was conducted at a single center, and although the surgical procedures were standardized and consistently performed, 97% were performed via laparoscopy, a technique that requires a steep learning curve, particularly for complex procedures. Furthermore, the relatively short follow-up period precluded the evaluation of long-term complications and recurrence rates.\u003c/p\u003e \u003cp\u003e \u003cb\u003eImplications of practice and future research-\u003c/b\u003eSentinel lymph node biopsy is expected to replace lymph node dissection in high risk endometrial cancer. These procedures will increasingly be performed using minimally invasive techniques. The future may see a paradigm shift towards tailoring surgery based on tumour\u0026rsquo;s molecular profile.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe sentinel lymph node (SLN) algorithm is a promising less invasive alternative to systematic pelvic lymphadenectomy. It offers the potential for the accurate detection of lymph node metastases while reducing surgical morbidity. However, larger multicenter studies with longer follow-up and incorporation of ultrastaging are needed to validate these findings and fully establish the clinical utility of the sentinel lymph node approach.\u003c/p\u003e \u003cp\u003e \u003cb\u003e​​\u003c/b\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003ch3\u003eEthics approval and consent to participate\u003c/h3\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki and its later amendments. Approval was obtained from the Institutional Ethics Committee, and written informed consent was obtained from all participants.\u0026nbsp;National board of examinations in medical sciences , medical enclave, Ansari nagar, new delhi India, reviewed the study and approved ethical and scientific clearance – number 2144105624\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDate of registration -30/6/2022\u003c/p\u003e\n\u003ch3\u003eConsent for publication\u003c/h3\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch3\u003eAvailability of data and materials\u003c/h3\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch3\u003eCompeting interests\u003c/h3\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch3\u003eFunding\u003c/h3\u003e\n\u003cp\u003eThis study received no external funding.\u003c/p\u003e\n\u003ch3\u003eAuthors’ contributions\u003c/h3\u003e\n\u003cp\u003eAK conceived and designed the study. AK and PA \u0026nbsp;collected the data. RI and ZU performed the data analysis. FZ and AK did the statistical work . AK,SR,RS and ASS drafted the manuscript. All authors critically revised the manuscript and approved the final version.\u003c/p\u003e\n\u003ch3\u003eAcknowledgements\u003c/h3\u003e\n\u003cp\u003eThe authors would like to thank the patients who participated in this study and the clinical staff involved in their care.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFerlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JWW, Comber H, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer. 2013 Apr;49(6):1374\u0026ndash;403. \u003c/li\u003e\n\u003cli\u003eShylasree TS, Bajpai J. Editorial on the topic: Gynecological cancers: A summary of published Indian data. Vol. 5, South Asian Journal of Cancer. Wolters Kluwer Medknow Publications; 2016. p. 111\u0026ndash;2. \u003c/li\u003e\n\u003cli\u003eJemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer Statistics, 2008. CA Cancer J Clin. 2008 Jan 28;58(2):71\u0026ndash;96. \u003c/li\u003e\n\u003cli\u003eYork N, Hospital P, Wright U (j D, Medel B, Herzog TJ, Charit\u0026eacute; ;, et al. Contemporary management of endometrial cancer. The Lancet [Internet]. 2012;379:1352\u0026ndash;60. Available from: www.thelancet.com\u003c/li\u003e\n\u003cli\u003eTirumani SH, Shanbhogue AKP, Prasad SR. Current Concepts in the Diagnosis and Management of Endometrial and Cervical Carcinomas. Vol. 51, Radiologic Clinics of North America. 2013. p. 1087\u0026ndash;110. \u003c/li\u003e\n\u003cli\u003eEpstein E, Blomqvist L. Imaging in endometrial cancer. Best Pract Res Clin Obstet Gynaecol. 2014;28(5):721\u0026ndash;39. \u003c/li\u003e\n\u003cli\u003eFaria SC, Sagebiel T, Balachandran A, Devine C, Lal C, Bhosale PR. Imaging in endometrial carcinoma. Indian Journal of Radiology and Imaging. 2015 May 1;25(2):137\u0026ndash;47. \u003c/li\u003e\n\u003cli\u003eCreasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer: A gynecologic oncology group study. Cancer. 1987;60(8 S):2035\u0026ndash;41. \u003c/li\u003e\n\u003cli\u003eBurke WM, Orr J, Leitao M, Salom E, Gehrig P, Olawaiye AB, et al. Endometrial cancer: A review and current management strategies: Part i. Vol. 134, Gynecologic Oncology. Academic Press Inc.; 2014. p. 385\u0026ndash;92. \u003c/li\u003e\n\u003cli\u003eSuchetha S, Mathew AP, Rema P, Thomas S. Pattern of Lymph Node Metastasis in Endometrial Cancer: a Single Institution Experience. Indian J Surg Oncol. 2021 Mar 1;12(1):73\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eRossi 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 Mar 1;18(3):384\u0026ndash;92. \u003c/li\u003e\n\u003cli\u003eDara\u0026iuml; 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(1):54\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003ePersson J, Salehi S, Bollino M, L\u0026ouml;nnerfors C, Falconer H, Geppert B. Pelvic Sentinel lymph node detection in High-Risk Endometrial Cancer (SHREC-trial)\u0026mdash;the final step towards a paradigm shift in surgical staging. Eur J Cancer. 2019 Jul 1;116:77\u0026ndash;85. \u003c/li\u003e\n\u003cli\u003ePersson J, Salehi S, Bollino M, L\u0026ouml;nnerfors C, Falconer H, Geppert B. Pelvic Sentinel lymph node detection in High-Risk Endometrial Cancer (SHREC-trial)\u0026mdash;the final step towards a paradigm shift in surgical staging. Eur J Cancer. 2019 Jul 1;116:77\u0026ndash;85. \u003c/li\u003e\n\u003cli\u003eCusimano 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 Feb 1;156(2):157\u0026ndash;64. \u003c/li\u003e\n\u003cli\u003eTogami S, Kubo R, Kawamura T, Yanazume S, Kamio M, Kobayashi H. Risk factors for lymphatic complications following lymphadenectomy in patients with endometrial cancer. Taiwan J Obstet Gynecol. 2020 May 1;59(3):420\u0026ndash;4. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8299344/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8299344/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003cbr\u003e\nEndometrial cancer is the sixth most common malignancy in women worldwide. While systematic lymphadenectomy provides prognostic information in high-risk cases, it increases perioperative morbidity without a consistent survival benefit. Although sentinel lymph node biopsy (SLNB) has been validated for low-risk disease, its role in intermediate to high-risk endometrial cancer remains uncertain.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e\u003cbr\u003e\nTo evaluate the diagnostic accuracy of laparoscopic indocyanine green (ICG)-guided SLNB in intermediate-to high-risk endometrial cancer as an alternative to complete lymphadenectomy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003cbr\u003e\nThis prospective, non-randomized, single-institute study included 47 women with presumed FIGO stage I–II high-risk endometrial cancer (July 2022–July 2024). National board of examinations India, reviewed the study and approved ethical and scientific clearance – number 2144105624 (30/6/2022)\u003c/p\u003e\n\u003cp\u003eAll patients underwent hysterectomy with bilateral salphingo-oophorectomy, laparoscopic ICG-guided pelvic and para aortic SLNB, and complete pelvic and para-aortic lymphadenectomy. ICG was injected into the cervix, and the diagnostic parameters were compared using full lymphadenectomy as the reference.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003cbr\u003e\nBilateral mapping was achieved in all cases with reinjection. Pelvic lymph node metastases were found in 6 patients (12.8%), with 5 identified by SLNB (sensitivity 83.3%, negative predictive value 100%). Para-aortic metastases occurred in 5 patients (10.6%), with 4 correctly identified (sensitivity 80%, Negative predictive value 80%). Diagnostic accuracy was 97.87% for pelvic and 88.89% for para-aortic nodes. Mean harvested nodes: 21 pelvic (range 6–34), 33 para-aortic (range 15–58). Nine patients (19.1%) had postoperative complications (mostly Clavien-Dindo grade I–II); readmission rate was 4.2%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003cbr\u003e\nICG-guided SLNB shows high negative predictive value and accuracy in intermediate to high-risk endometrial cancer. It offers a reliable, less invasive alternative to complete lymphadenectomy, potentially reducing surgical morbidity without compromising diagnostic efficacy.\u003c/p\u003e","manuscriptTitle":"Laparoscopy guided Indocyanine Green-Guided Pelvic and Para-Aortic Sentinel Lymph Node Mapping in High-Risk Endometrial Cancer: A Step Toward Precision Staging","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-22 08:25:22","doi":"10.21203/rs.3.rs-8299344/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-17T12:49:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"309443613662656701847576015929461905546","date":"2026-02-04T21:50:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-29T07:07:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"130281782207728764735504673164773678636","date":"2026-01-20T23:27:02+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-20T10:59:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-19T08:07:25+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-26T10:10:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-26T08:46:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-12-26T08:40:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0ef0c486-831b-4d8d-b097-bd1da8457d30","owner":[],"postedDate":"January 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-22T08:25:23+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-22 08:25:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8299344","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8299344","identity":"rs-8299344","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}