Bogani G, Murgia F, Ditto A, Raspagliesi F. Sentinel Node Mapping vs. Lymphadenectomy in Endometrial Cancer: A Systematic Review and Meta-Analysis. (82) found out that, in the early-stage patients, the DR of positive pelvic lymph nodes in SLN group (145 patients) was higher than in LAD group (657 patiens) (16.7% vs. 7.3%; p = 0.002), including 80 type II EC, and there was no difference observed in 3-year RFS and mortality between the two groups. In addition, A cohort study with 5546 patients published by Polcher etal. (91) drew comparison of the perioperative outcomes for TH + BSO, TH + BSO + SLN, and TH + BSO + LAD groups. doi: 10.1016/j.ygyno.2020.09.023, 121. Gynecol Oncol (2001) 80(2):13944. Schiavone MB, Zivanovic O, Zhou Q, Leitao MM Jr, Levine DA, Soslow RA, et al. Survival of Patients With Serous Uterine Carcinoma Undergoing Sentinel Lymph Node Mapping. Moloney K, Janda M, Frumovitz M, Leitao M, Abu-Rustum NR, Rossi E, et al. Although non-SLN metastases could be controlled by adjuvant therapy and the promising results of high-risk EC patients support the hypothesis, the appropriate management of non-SLN is still worthy of further studies. doi: 10.1016/j.ygyno.2013.01.022, 100. Geppert B, Lonnerfors C, Bollino M, Persson J. Sentinel Lymph Node Biopsy in Endometrial Cancer-Feasibility, Safety and Lymphatic Complications. Since its definition in 1988, surgical staging in endometrial cancer (EMCA) has been controversial. It is called MSKCC algorithm and is recommended in NCCN guideline. Sensitivity is defined as the proportion of patients with positive SLN to the total number of patients with metastasis. (138) found out that 60.8% of non-SLNs were positive when SLN was found to harbor macro-metastases. Niikura H, Okamoto S, Yoshinaga K, Nagase S, Takano T, Ito K, et al. doi: 10.1097/IGC.0000000000000387, 56. Surgery plays a fundamental role in the treatment of endometrial and cervical cancer. Eur J Cancer (2020) 140:110. (124). Further studies should be carried on to evaluate the effect of leaving metastatic non-SLNs in-situ. doi: 10.2147/BCTT.S113737, 155. Farghali MM, Allam IS, Abdelazim IA, El-Kady OS, Rashed AR, Gareer WY, et al. The BDR was as high as 95%, and no adverse effect occurred (72). CA Cancer J Clin (2021) 71(1):733. Retrospective Validation of the Laparoscopic ICG SLN Mapping in Patients With Grade 3 Endometrial Cancer. A randomized non-inferiority trial of 180 patients with uterine and cervical cancer showed that, ICG detected 97% of the total lymph nodes dissected whereas blue dye identified only 47% (38). Altin D, Takn S, Kahramanoglu I, et al. The dye can reach lymphatic vessels and lymph nodes around the tumor, and SLN is the first lymph node to show color. Clin Nucl Med (2015) 40(10):7805. Clinical Analysis of 76 Cases of Sentinel Lymph Node Detection in Cervical Cancer and Endometrial Cancer. Raimond E, Ballester M, Hudry D, Bendifallah S, Dara E, Graesslin O, et al. Though the two studies are blamed for varying design defects, such as LAD group, did not perform PALAD, the two groups of high-risk patients were not balanced, the proportion of low-risk patients was larger, and adjuvant therapy was not standardized, but it did arouse intensive debates (15). World J Surg Oncol (2018) 16(1):95. doi: 10.1186/s12957-018-1392-8, 51. Though there are no RCTs published yet, existing evidence indicates that SLNM may be also efficient and safe in high-risk group, MSKCC has already established SLNM as a routine procedure for all candidate patients, including serous and carcinosarcoma type. A more recent multicenter study performed by Bougherara etal. The authors suggested that SLNM may be superior to LAD due to the removal of lymph nodes at a higher risk of metastasis. (65) indicated that the DR and sensitivity was 78% and 93%, respectively. Mueller JJ, Pedra Nobre S, Braxton K, Alektiar KM, Leitao MM Jr, Aghajanian C, et al. Uterine Neoplasms, Version 3. Gynecol Oncol (2015) 136(1):604. Euscher E, Sui D, Soliman P, Westin S, Ramalingam P, Bassett R, et al. J Natl Compr Cancer Network (2014) 12(2):28897. Surgeons must strictly follow the technical details and SLN algorithm in operation, including superficial and deep injection of cervix, thorough evaluation of abdominal and pelvic cavity, resection of all SLN and suspicious enlarged lymph nodes, additional LAD on unmapped side when SLN mapping failure occurs and ultra-staging pathology is performed in combination with routine H&E. J Oncol (2019) 2019:3415630. doi: 10.1155/2019/3415630, 26. doi: 10.1097/PGP.0000000000000552, 27. The most recent multi-institutional retrospective study performed by Bogani etal. doi: 10.1007/s10147-016-1030-9, 154. Rev Obstet Gynecol (2012) 5(1):2834, 10. M.D. Touhami O, Gregoire J, Renaud MC, Sebastianelli A, Plante M. Performance of Sentinel Lymph Node (SLN) Mapping in High-Risk Endometrial Cancer. J Clin Med (2020) 10(1):120. doi: 10.3390/jcm10010120, 98. A Comparison of Sentinel Lymph Node Biopsy to Lymphadenectomy for Endometrial Cancer Staging (FIRES Trial): A Multicentre, Prospective, Cohort Study. doi: 10.1007/s11701-019-00928-z, 127. doi: 10.1016/S1470-2045(11)70070-5, 63. If the H&E staining and/or ultra-staging of SLN is positive after surgery, patients can either choose adjuvant therapy or a second operation. Int J Gynecol Cancer (2020) 30(3):2918. Buda A, Restaino S, Di Martino G, De Ponti E, Monterossi G, Dinoi G, et al. They found out that the sensitivity and NPV of SLNM were 95.8% and 98.2%, respectively (104). Uterine corpus injection includes hysteroscopic or transvaginal ultrasound-guided peritumoral (subendometrial) injection (53) preoperatively and subserosal or myometrial injection intraoperatively. Niikura H, Kaiho-Sakuma M, Tokunaga H, Toyoshima M, Utsunomiya H, Nagase S, et al. The pelvic lymph node metastasis rate (including LVMD) was 5.1% and 2.6% (p=0.03), respectively, while the PAL metastasis rate was 0.8% and 1.0% (p=0.75), respectively. doi: 10.1016/j.ygyno.2015.04.008, 139. We describe the feasibility of laparoscopic intraoperative sentinel node identification with cervical stump removing to restage the suspicious early stage high risk endometrial cancer. doi: 10.1016/S1470-2045(18)30079-2, 132. Curr Oncol Rep (2018) 20(12):96. doi: 10.1007/s11912-018-0744-4, 16. Sentinel Node Mapping in Endometrial Cancer: Tips and Tricks to Improve Bilateral Detection Rate. The DR ranges from 73% to 100%, the BDR varies from 56% to 95%, and NPV ranges from 93% to 100% (5, 42, 53, 72, 92, 99107). Two-Step Sentinel Lymph Node Mapping Strategy in Endometrial Cancer Staging Using Fluorescent Imaging: A Novel Sentinel Lymph Node Tracer Injection Procedure. Lancet Oncol (2011) 12:46976. Despite this, it did reduce the need for LAD and the probability of surgical injury. However, there was no difference spotted in the detection of cases with lymph node metastasis found every year (Y1 7.0%, Y2 7.9%, Y3 7.5%, p = 1.0), so SLNM failed to reduce the diagnosis of stage IIIC. In addition, Renz etal. There are no adverse reactions reported yet, and the DR is quite high. Intraabdominal Lymphatic Mapping to Direct Selective Pelvic and Paraaortic Lymphadenectomy in Women With HighRisk Endometrial Cancer: Results of a Pilot Study. Kostun J, Pesta M, Slama J, Slunko R, Vlask P, Bouda J, et al. Pathol Oncol Res (2020) 26(4):204956. Overall, Cormier etal. Besides, further improvement in the diagnostic accuracy and therapeutic safety of SLNM are in urgent need to provide more personal and minimal-invasive treatment for EC patients and make a difference to their prognosis. Abu-Rustum NR. Predictors of Non-Sentinel Lymph Node (Non-SLN) Metastasis in Patients With Sentinel Lymph Node (SLN) Metastasis in Endometrial Cancer. doi: 10.1245/s10434-015-5040-z, 143. doi: 10.1016/j.ejso.2018.06.034, 117. Lymph node status plays a crucial role in evaluating the prognosis and selecting adjuvant therapy. doi: 10.1016/j.ygyno.2017.09.014, 105. (83), the outcomes of 125 stage I-II EC patients were assessed. Theoretically, if SLN is negative, lymphatic metastasis of the drainage area does not occur yet, thus avoiding LAD with following surgical trauma (11). The role of backup LAD for high-risk cases remains areas of investigation. SLNM can remove fewer lymph nodes with sufficient staging information supporting adjuvant therapy, and will not cause the possibility of post-operative complications to increase compared with hysterectomy alone (7). Received: 28 April 2021; Accepted: 01 June 2021;Published: 29 June 2021. Gynecol Oncol (2015) 136(1):549. Comparison Between Laparoscopic and Robotic Surgery for Sentinel Lymph Node Mapping in Endometrial Cancer Using Indocyanine Green and Near Infra-Red Fluorescence Imaging. It is the most recommended tracer in researches and guidelines, especially for patients with minimally invasive surgery and obesity, due to its highest DR and bilateral detection rate (BDR) (3537). Incidence, Risk Factors and Estimates of a Womans Risk of Developing Secondary Lower Limb Lymphedema and Lymphedema-Specific Supportive Care Needs in Women Treated for Endometrial Cancer. As a result, the SLN arm has a sensitivity of 90%, an NPV of 95.7%, and an FNR of 4.3%. In 2021, there will be an estimated 66,570 new cases and 12,940 deaths, making uterine cancer the second most prevalent cancer in women in U.S. after breast cancer (1). Khoury-Collado F, Glaser GE, Zivanovic O, Sonoda Y, Levine DA, Chi DS, et al. To improve the sensitivity and NPV, MSKCC proposed that, unilateral or bilateral LAD should be added if SLN map failure occurs in one side or both sides, all suspicious enlarged lymph nodes and peritoneal lesions should be removed, and ultra-staging pathology should be performed after operation. 2nd ed. doi: 10.1016/j.ygyno.2019.10.005, 119. Some methylene blue may leak into the capillaries, resulting in reduced dye volume in lymphatic pathway and decreased SLN DR (32). believed that the patients with MM detected in SLN should receive adjuvant therapy, whereas whether ITC undergoes adjuvant therapy depends on uterine factors (130). Current Landscape and Future Perspective of Sentinel Node Mapping in Endometrial Cancer. performed SLNM+LAD+PALAD under 123 high-risk patients. J Natl Compr Cancer Network JNCCN (2014) 12(2):28897. Similar results were reached by Biocchi, 54.5% macrometastasis and 15.4% micrometastasis were found non-SLN involvement, whereas in patients with ITCs in SLN, no metastasis was found in non-SLN (161). A multicenter RCT showed that hysteroscopic injection has a higher rate in identifying PAL (29% vs. 19.5, p=0.18) and IPL (5.8% vs. 0%) than cervical injection; however, there is no statistical difference (57). Eitan R, Sabah G, Krissi H, Raban O, Ben-Haroush A, Goldschmit C, et al. Usually, patients with positive pelvic lymph nodes would receive adjuvant therapy, which could eliminate the possible aortic lesions in theory, for SLNM with ultra-staging has an excellent ability to detect pelvic metastasis with high sensitivity and NPV. Also, researchers have developed strategies like dual site injection (156) or reinjection (72) to increase the detection of aortic SLN to reduce FNR. showed a 73.1% DR, 94.4% sensitivity, and 100% specificity in 93 high-risk patients (100). Lymphatic Mapping and Sentinel Node Biopsy in Women With High-Risk Endometrial Cancer. Incidence of Pelvic Lymph Node Metastasis Using Modern FIGO Staging and Sentinel Lymph Node Mapping With Ultrastaging in Surgically Staged Patients With Endometrioid and Serous Endometrial Carcinoma. Sentinel Node Mapping in Cervical and Endometrial Cancer: Indocyanine Green Versus Other Conventional Dyes-a Meta-Analysis. (87) compared the long-term oncologic results of SLNM, SLNM+LAD and LAD. Some institutions are making attempt to apply SLNM as routine surgical staging in all EC patients, except for patients with suspected lymph-node metastasis or failed mapping. Multicenter Study Comparing Oncologic Outcomes Between Two Nodal Assessment Methods in Patients With Deeply Invasive Endometrioid Endometrial Carcinoma: A Sentinel Lymph Node Algorithm Versus a Comprehensive Pelvic and Paraaortic Lymphadenectomy. Kumar et al. 3rd. Eur J Cancer (2019) 116:7785. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol (2021) 47(6):123343. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Liu CY, Elias KM, Howitt BE, Lee LJ, Feltmate CM. ICG and cervical injection has gained worldwide acceptance for its ability in detecting SLN with a relatively high sensitivity. Federal government websites often end in .gov or .mil. doi: 10.1245/s10434-019-08045-9, 162. Sentinel lymph node mapping in endometrial cancer - areas where further research is needed. The method features simplicity and cost-effectiveness. doi: 10.1002/1097-0142(196001/02)13:1<77::aid-cncr2820130114>3.0.co;2-d, 29. Torne etal. Cervical and Hysteroscopic Injection for Identification of Sentinel Lymph Node in Endometrial Cancer. ICG and cervical injection could increase the DR (p < 0.05). Researches have demonstrated high DR, sensitivity, and NPV in patients with early-stage EC using SLNM with pathologic ultra-staging. Also, there are studies addressing the problem and comparing the oncologic outcomes between SLN and more extensive LAD with or without SLN, preliminary results suggested that there are no difference in these approaches (87, 118). J Minim Invasive Gynecol (2018) (6):112532. The surgeon then looks for the lymph nodes that turn blue or green (from . However, the therapeutic role and survival benefit of LAD have been in controversial in recent years with the publication of a series of high-quality research. Lancet Oncol (2018) 19(3):295309. Improving Sentinel Lymph Node Detection Rates in Endometrial Cancer: How Many Cases Are Needed? Gynecol Oncol (2017) 147(3):52834. Gynecol Oncol (2017) 147(1):1205. The Role of Lymphadenectomy Versus Sentinel Lymph Node Biopsy in Early-stage Endometrial Cancer: A Review of the Literature. National Comprehensive Cancer Network. Ditto A, Casarin J, Pinelli C, Perrone AM, Scollo P, Martinelli F, et al. Studies have been carried out to compare the oncologic outcome of SLNM-only vs. LAD without SLNM, or SLNM only vs. SLNM+LAD, or SLNM+LAD vs. LAD group, suggesting that SLNM failed to compromise survival outcome. The Evolving Role of One-Step Nucleic Acid Amplification (OSNA) for the Intra-Operative Detection of Lymph Node Metastases: A Diagnostic Accuracy Meta-Analysis. doi: 10.1136/ijgc-2018-000113, 150. SLNM gradually became a routine procedure for the treatment of breast cancer and skin melanoma. National Cancer Institute Foundation (IRCCS), Italy. Twenty-five percent of deeply invasive G1/G2 and 18% of deeply invasive G3 tumors had ITCs compared to a rate lower than 1% in non-invasive endometroid EC patients. As a result, the LVMD group shows a significant increase in 3 year-RFS compared with the macro-metastases group (86 vs. 71%, p <0.001), as most LVMD receive adjuvant therapy. Furthermore, staging protocol was re-edited in 2009 for setting IIIC1 as positive pelvic lymph nodes, while IIIC2 refers to the positive para-aortic lymph nodes (10). Chaowawanit W, Campbell V, Wilson E, Chetty N, Perrin L, Jagasia N, et al. Moreover, prospective and retrospective studies indicated that SLNM appears to have no negative impact on oncologic outcomes in high-risk EC patients (Table2). Comparison of a Sentinel Lymph Node Mapping Algorithm and Comprehensive Lymphadenectomy in the Detection of Stage IIIC Endometrial Carcinoma at Higher Risk for Nodal Disease. NPV refers to the proportion of patients with SLN-negative and confirmed that no other lymph node metastasis to the total number of patients with SLN-negative. Patients with pelvic or para-aortic lymph node metastasis has dramatically decreased survival rate (10). The author considered the risk of missing IPL of SLNM in high-risk patients may be the reason, a large-scale multicenter study was needed to clarify the result. doi: 10.1016/j.ygyno.2015.05.039, 50. Data from our hospital showed that the combination of CNP and ICG resulted a higher BDR of SLN in cervical and endometrial cancer comparing to CNP or ICG alone (p<0.05) (45, 46). Immediate Intraoperative Sentinel Lymph Node Analysis by Frozen Section is Predictive of Lymph Node Metastasis in Endometrial Cancer. Ruiz R, Gorostidi M, Jaunarena I, Goiri C, Aguerre J, Lekuona A. Schiavone MB, Scelzo C, Straight C, Zhou Q, Alektiar KM, Makker V, et al. Also, the use of the entire lymph node avoids insufficient analysis of pathology, thus increasing the identification of metastatic lesions. doi: 10.1016/j.ejca.2020.08.030, 58. The Incidence of Isolated Paraaortic Nodal Metastasis in Surgically Staged Endometrial Cancer Patients With Negative Pelvic Lymph Nodes. Frozen Section Analyses as Predictors of Lymphatic Spread in Patients With Early-Stage Uterine Cancer. To do this, a blue or green dye is injected into the area with the cancer, near the cervix. Compton CC, SpringerLink ebooks M, American Joint Committee on C. AJCC Cancer Staging Atlas: A Companion to the Seventh Editions of the AJCC Cancer Staging Manual and Handbook. pointed out that LAD and PALAD are independent risk for lymphedema and lymphocele (6). Patient-Reported Outcomes After Surgery for Endometrial Carcinoma: Prevalence of Lower-Extremity Lymphedema After Sentinel Lymph Node Mapping Versus Lymphadenectomy. J Surg Oncol (2019) 119(3):3619. Furthermore, SLNM exerted no impact on recurrence-free survival (RFS). A Multicenter Italian Study. developed transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR), presenting an 82.1% DR, 92.3% sensitivity, and 97.7% NPV (53). Otherwise, only 5% non-SLN was positive when SLN had LVMD. Gynecol Oncol (2017) 146(2):2349. Cancer (1960) 13:778. Schwartz GF, Giuliano AE, Veronesi U, Consensus Conference C. Proceedings of the Consensus Conference on the Role of Sentinel Lymph Node Biopsy in Carcinoma of the Breast, April 19-22, 2001, Philadelphia, Pennsylvania. While in the latest consensus and surgical assessment tool, which aims to standardize the surgical technique and quality of SLNM in EC, it also recommends cervical injection of ICG, however, when mapping failure occurs, it points out 4 choices: waiting and turning to contralateral side, exploring the uncommon regions like presacral, common iliac or para-aortic area, re-injection of tracer, or performing side specific LAD (61). (63), the DR was 81%. J Surg Oncol (2021) 123(2):63845. SLN mapping is a form of image-guided surgery that can enhance a surgeon's ability to find the SLN, or the purported first node involved in lymphatic metastases from the primary cancer. The Incidence of Isolated Para-Aortic Nodal Metastasis in Completely Staged Endometrial Cancer Patients. Nowadays, it is trending to carry on SLNM in early-stage high-risk EC, including high-risk histology (G3 endometroid, serous carcinoma, clear cell carcinoma, and carcinosarcoma), deep myometrial invasion, cervical involvement, and LVSI (+). Nasioudis D, Albright BB, Roy A, Ko EM, Giuntoli RL 2nd, Haggerty AF, et al. from France analyzed 248 EC patients between 2007 and 2018 undergone SLN procedure, as a result, the 3-year OS was 99% and 3-year RFS was 92% (89). Among SLN positive, 8.1% were detected by ultra-staging. As compared to a full lymphadenectomy in every patient, to a selective lymphadenectomy after frozen section of uterus in selected patients with intrauterine risk factors or to a strategy in which a lymphadenectomy is always omitted, SLN mapping seems to be a reasonable and . As revealed by the recent studies, SLNM may also be feasible, effective, and safe in high-risk patients. Gynecol Oncol (2014) 133(3):50611. Torn A, Pahisa J, Vidal-Sicart S, Martnez-Roman S, Paredes P, Puerto B, et al. Besides, the positive lymph node DR is significantly increased in SLN group compared with LAD group (26.7% vs. 14.3%, p=0.02) (106). An Approach for the Treatment of Penile Carcinoma. Description of a Reproducible Anatomically Based Surgical Algorithm for Detection of Pelvic Sentinel Lymph Nodes in Endometrial Cancer. Can Risk Groups Accurately Predict non-Sentinel Lymph Node Metastasis in Sentinel Lymph Node-Positive Endometrial Cancer Patients? In an ideal clinical research, the patients should be randomly assigned into SLNM arm or LAD arm, and receive standard post-operative adjuvant therapy according to stage information (40). The FIRES study (64) included 385 patients with EC from 19 surgeons in 10 institutions. Todo Y, Kato H, Okamoto K, Minobe S, Yamashiro K, Sakuragi N. Isolated Tumor Cells and Micrometastases in Regional Lymph Nodes in Stage I to II Endometrial Cancer. It is noted that the detection of metastatic PAL was similar between SLN group and LAD group even in high-risk histology type EC (106, 117), which indicates that SLNM does not compromise the detection of PAL metastases in high-risk patients. doi: 10.3322/caac.21561, 25. Du J, Li Y, Wang Q, Batchu N, Zou J, Sun C, et al. J Minim Invasive Gynecol (2020) 27(2):4828. Naoura I, Canlorbe G, Bendifallah S, Ballester M, Darai E. Relevance of Sentinel Lymph Node Procedure for Patients With High-Risk Endometrial Cancer. (50) found out that patients with ITC and MM received more adjuvant therapy and presented much better oncologic outcomes. Eur J Gynaecol Oncol (2015) 36(6):6436. (73) and Ruiz etal. When pelvic lymph nodes are positive, 51% have PAL metastases. Sentinel Lymph Node Mapping in Endometrial Cancer: A Systematic Review and Meta-Analysis. Gynecol Oncol (2020) 159(3):7326. doi: 10.1016/j.ygyno.2012.02.021, 64. The standard set by SGO about LVMD is based on breast cancer guidelines published by AJCC (132): macro-metastasis (>2 mm); low-volume metastases (LVM), including micro-metastasis (MM) (0.22 mm) and isolated tumor cells (ITCs) (< 0.2 mm). However, this study can only prove that SLNM + LAD reduced the recurrence rate compared with LAD alone, for which it can hardly prove the advantages of SLNM alone. Sentinel lymph node (SLN) sampling, first described in 1996, was established to be as accurate as systematic lymphadenectomy in evaluating the nodal status of early endometrial cancer and is now the standard of care in most gynecologic oncology units. Recent data tend to consider patients with MM for a following adjuvant therapy, whereas patients with ITCs do not. Whereas when pelvic lymph nodes are negative, PAL metastases, namely IPL metastasis, are found in 3% patients. Int J Gynecol Cancer (2020) 30(7):100511. (21) demonstrated that lymph node metastatic rate for para-aortic region and pelvic cavity is similar (12% vs. 17%). Learn what to expect during this procedure to remove lymph nodes for testing. doi: 10.3802/jgo.2016.27.e1, 141. doi: 10.1097/MNM.0000000000001157, 114. Comparison of a Sentinel Lymph Node and a Selective Lymphadenectomy Algorithm in Patients With Endometrioid Endometrial Carcinoma and Limited Myometrial Invasion. Sentinel Lymph Node Mapping Alone Compared to More Extensive Lymphadenectomy in Patients With Uterine Serous Carcinoma. doi: 10.1136/ijgc-2018-000084, 7. Sentinel lymph node detection is an alternative to assess lymphatic spread in several solid tumors. Gynecol Oncol (2017) 144(3):5039. Mounting evidence has demonstrated good sensitivity and specificity of OSNA in identifying positive nodes, especially micro-metastasis, in endometrial cancer (147150). Pathological assessment methods for lymph nodes include H&E and IHC staining. 1 Given the low risk of lymph node metastases in early-stage disease, it is believed that performing a pelvic (PLND) and para-aortic lymphadenectomy (PALND) in every patient is harmful rather than helpful. The Impact of Sentinel Node-Mapping in Staging High-Risk Endometrial Cancer. False negative rate (FNR) refers to the proportion of patients with negative SLN but non-SLN positive to the total number of patients with SLN metastasis. How J, Gauthier C, Abitbol J, Lau S, Salvador S, Gotlieb R, et al. Int J Gynecol Pathol (2018) 37(3):24251.doi: 10.1097/PGP.0000000000000415. Application of a Carbon Nanoparticle Suspension for Sentinel Lymph Node Mapping in Patients With Early Breast Cancer: A Retrospective Cohort Study. conducted a systematic review of cervical injection in 1,102 cases and corpus injection in 300 cases, which led to a conclusion that the overall DR of cervical injection ranged from 62% to 100%, corpus injection varied from 73% to 95% (49), and the DR of PAL was 39%, 17%, and 2%, respectively, in fundus, deep cervix, and superficial cervix injection (49). A Prospective Validation Study of Sentinel Lymph Node Mapping for High-Risk Endometrial Cancer. Am J Obstet Gynecol (2017) 216(5):459476 e410. In stage 2 of uterine cancer, the lymph nodes in the uterus start to expand into cervix tissue. It owns the advantages of unique lymphatic system tendency, small-size, fast diffusion, and long-lasting color rendering (43). J Robotic Surgery (2020) 14(1):3540. To reduce the . Use of a Novel Sentinel Lymph Node Mapping Algorithm Reduces the Need for Pelvic Lymphadenectomy in Low-Grade Endometrial Cancer. Moreover, MSKCC and Mayo Clinic investigated 176 deeply invasive endometrioid EC in 2018. Gould EA, Winship T, Philbin PH, Kerr HH. Anatomical study has proven that EC can directly metastasize into PAL through pelvic-infundibular ligament pathway. Patterns of Use and Outcomes of Sentinel Lymph Node Mapping for Patients With High-Grade Endometrial Cancer. Bodurtha Smith AJ, Fader AN, Tanner EJ. doi: 10.1136/ijgc-2019-000923, 42. However, the method relies on near-infrared device (40). It is stable because of the rarity of cervical deformation caused by uterine fibroids, tumor infiltration or conization history (48). Most recently, Bogani etal. Comparison Study of Laparoscopic Sentinel Lymph Node Mapping in Endometrial Carcinoma Using Carbon Nanoparticles and Lymphatic Pathway Verification. Tschernichovsky R, Diver EJ, Schorge JO, Goodman A. ClinicalTrials.gov Identifier: NCT03778255 (86) indicated that LAD failed to improve DFS or OS compared with SLNM. Endometrial cancer (EC) is known as a common female genital malignancy with rapidly increasing incidence these years. Todo et al analyzed 61 EC patients with intermediate risk for recurrence (140). While, Chaowawanit et al summarized 76 patients with laparoscopic surgery and 33 patients with robotic approach. (126) from Stanford University and Bellaminutti etal. Anderson Cancer Center SLN ultra-staging protocol. Bogoni etal. (155) summarized 18 papers and concluded that the incidence of IPL metastasis is as low as 1.7%. Oncol. In 1960, Gould etal. Gynecol. Gynecol Oncol (2017) 145(1):504. Curr Treat Options Oncol (2017) 18(10):62. doi: 10.1007/s11864-017-0503-z, 41. (127) from Switzerland found that adding intraoperative FS to SLN can find micrometastases with a good accuracy, and NPV, thus, may identify patients who are in need for a systemic LAD for dissecting additional lymph node metastases. Previous studies are typically performed on early-stage EC patients with mostly patients with lower-risk of recurrence and fewer higher-risk included. Takin S, Varli B, Ersz CC, Altin D, Soydal , Orta F. Complementary Role of 18F-FDG PET/CT for Sentinel Lymph Node Algorithm in Endometrial Cancer With High-Risk Factors for Lymphatic Metastasis. Lack of RCTs, long-term follow-up studies, standardized SLNM technique, and ultra-staging protocol, as well as adjuvant therapy are the primary concern. Accuracy of Sentinel Node in Detecting Lymph Node Metastasis in Primary Endometrial Carcinoma. In a study of women with high-grade endometrial cancer, researchers at The University of Texas MD Anderson Cancer Center, found sentinel lymph node (SLN) mapping accurately identified all women with node-positive, high-risk endometrial cancer, when prospectively compared to a complete pelvic and para-aortic lymphadenectomy (LAD), the current standard of care. The sentinel lymph node (SLN) mapping algorithm has emerged as an acceptable alternative to conventional pelvic and para-aortic lymph node dissection in endometrial cancer. Favero G, Pfiffer T, Ribeiro A, Carvalho JP, Baracat EC, Mechsner S, et al. Gynecol Oncol (2017) 145(2):24855. Ballester M, Dubernard G, Lcuru F, Heitz D, Mathevet P. Detection Rate and Diagnostic Accuracy of Sentinel-Node Biopsy in Early Stage Endometrial Cancer: A Prospective Multicentre Study (SENTI-ENDO). However, it is noted that most institutions only perform ultra-staging on SLN but non-SLN due to many factors, which may underestimate the incidence of LVMD in non-SLN. This content does not have an English version. Yabushita etal. Facts Views Vis Obgyn (2020) 11(4):32328. MC carefully revised the manuscript. Pathologic Ultrastaging Improves Micrometastasis Detection in Sentinel Lymph Nodes During Endometrial Cancer Staging. doi: 10.6004/jnccn.2014.0026, 53. Despite lack of RCTs and long-term follow-up studies, existing evidence advocate the utilization of SLNM in uterine-confined EC even in high-risk histology because of sufficient detection rate of SLN and nodal metastases, and similar survival outcome compared with conventional LAD. 110. Eoh KJ, Lee YJ, Kim HS, Lee JY, Nam EJ, Kim S, et al. Fanfani F, Monterossi G, Di Meo ML, La Fera E, Dell'Orto F, Gio A, et al. 78. Laparoscopic Sentinel Node Mapping With Intracervical Indocyanine Green Injection for Endometrial Cancer: The SENTIFAIL Study - A Multicentric Analysis of Predictors of Failed Mapping. Though subserosal injection at fundus is relatively easy, it remains difficult to show the parametrial lymphatic drainage, and most early ECs do not invade or penetrate to the serosa layer. The sensitivity and NPV were unexpectedly as low as 20% and 83.3%, with a surprisingly high FNR of 80%. (146) obtained a 5% of LVMD in SLN, compared to merely 0.3% in non-SLN. Similar results were obtained by Sinno etal. The results showed that SLNM cohort (118 patients) did not increase lymphatic recurrence and exhibit a similar OS (88% vs. 77%, p=0.06) with LAD cohort (96). The DR ranged from 73% to 100%, the DR of PAL ranged between 13% and 56%, and the DR of IPL ranged from 3.4% to 20% (5456). *Correspondence: Jianliu Wang, wangjianliu@pkuph.edu.cn, Future Perspectives of Sentinel Node Mapping in Gynecological Oncology, View all Gynecol Oncol (2017) 147(3):5418. Accuracy of One-Step Nucleic Acid Amplification in Detecting Lymph Node Metastases in Endometrial Cancer. Compared with ultra-staging, OSNA is much faster thus can be done intraoperatively; moreover, it identified more SLN involvement, resulting in 20.69% of patients upstaged as FIGO stage III (150). (3) demonstrated that LAD brings no survival benefits in intermediate-risk EC group and Zhang etal. This practice lets the doctor understand the exact stage the cancer is in while potentially slowing the spread of the disease through the removal of cancerous cells. Better standardization of SLNM protocol, surgical training program, and ultra-staging technique are also needed. Moreover, it is difficult for obese patients and patients with severe internal complications to tolerate LAD. doi: 10.1016/j.suronc.2010.10.002, 34. doi: 10.1016/j.ygyno.2019.04.002, 87. J Minim Invasive Gynecol (2020) 27(4):93845.e2. Implications for Practice: Lymphatic mapping is an increasingly popular option in the surgical treatment of endometrial cancer. Sentinel Lymph Node Mapping in Patients With Stage I Endometrial Carcinoma: A Focus on Bilateral Mapping Identification by Comparing Radiotracer Tc99(m) With Blue Dye Versus Indocyanine Green Fluorescent Dye. J Cancer Res Clin Oncol (2017) 143(3):47580. concluded that ITC incidence increased with depth of myoinvasion. Compared to node-negative patients, a noticeable 20% decrease was observed in 8-year OS and PFS in LVMD patients. Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology. Bellaminutti S, Bonollo M, Gasparri ML, Clivio L, Migliora P, Mazzucchelli L, et al. The results showed a 14.8% incidence of LVMD and deep myometrial invasion was significantly associated with ITC/MM (p=0.028). Gynecol Oncol (2009) 115(3):4535. While LAD laid more risk on intraoperative complications (HR, 14.25;95% CI, 1.8519.63), postoperative complications (HR, 3.11; 95% CI, 1.625.98), and lower-extremity lymph edema (HR, 8.14; 95% CI, 1.0165.27). The results can show whether cancer has spread. SLNM is supposed to show high sensitivity and low FNR. doi: 10.1002/jso.26338, 40. When coming to non-invasive serous type, the incidence for ITC goes up to 10% (141). The combined method is usually a combination of TC-99 and blue dye or ICG. J Natl Compr Cancer Network JNCCN (2018) 16(2):17099. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol (2018) 44(10):15627. Int J Gynecol Cancer (2021) 31(5):64755. Bogani G, Raspagliesi F, Leone Roberti Maggiore U, Mariani A. Meantime, NCCN also permits the potential use of SLNM in early-stage high-risk EC patients like serous carcinoma, clear cell carcinoma and carcinosarcoma (123). It enters the lymphatic system by macrophage and is excreted through the respiratory and gastrointestinal tract (44). As revealed by the FIRES studies, 17% of lymph node-positive patients were found in non-traditional sites (presacral, parametrial areas, and deep iliac) (64). Solima E, Brusati V, Ditto A, Kusamura S, Martinelli F, Hanozet F, et al. J Natl Cancer Institute (2008) 100(23):170716. The DR of pelvic SLN is higher using cervical injection as confirmed by large-scale studies (more than 100 patients), with a rate over 80% normally (49). Cabrera suggested adding Tc-99m to ICG for the increased BDR (69% vs. 41%, p = 0.012) and decreased empty node rate (0% vs. 4%, p = 0.032), which is known as a disadvantage to ICG alone (41). Touhami et al. doi: 10.1016/j.ygyno.2009.08.026, 70. Combination of Sentinel Lymph Node Mapping and Uterine Frozen Section Examination to Reduce Side-Specific Lymphadenectomy Rate in Endometrial Cancer: A Turkish Gynecologic Oncology Group Study (TRSGO-SLN-002). Kumar S, Podratz KC, Bakkum-Gamez JN, Dowdy SC, Weaver AL, McGree ME, et al. Perissinotti A, Paredes P, Vidal-Sicart S, Torn A, Albela S, Navales I, et al. Whether to perform PALAD is at the discretion of the surgeon (48). The false negative SLN was more likely to appear in unilateral mapping failure patient. Cancer (2002) 94(10):254251. Kogan et al (88) compared 193 EC patients with LAD and 250 patients with SLN+LAD. You may notice unusual bleeding and discharge of vaginal fluid. SLN + LAD improved the DR of lymph node metastasis (OR3.29, p < 0.001). Staging of High-Risk Endometrial Cancer With PET/CT and Sentinel Lymph Node Mapping. Sentinel lymph node (SLN) mapping is becoming an acceptable alternative to full lymphadenectomy for evaluating lymphatic spread in clinical stage I endometrial cancer (EC). AJCC (133) set term pN0 (i+) for ITCs and pN1mi for MM in breast cancer. Singh V, Chaudhary A, Modi KB, Singh LS, Roy L, Dougall P, et al. Frumovitz M, Plante M, Lee PS, Sandadi S, Lilja JF, Escobar PF, et al. doi: 10.1016/S0140-6736(08)61766-3, 15. Gynecol Oncol (2012) 126(3):41923. Radioactive tracers like technetium(Tc)-99m can remain highly concentrated in the SLN, and emit gamma-rays, which will be detected by gamma detector and single-photon emission computed tomography (SPECT-CT). Figure2 (A) MSKCC SLN ultra-staging protocol. Am J Clin Oncol (2016) 39(5):51621. In the same year, Buda etal. 77. A major challenge in implementing SLNM lies in the potential of residual metastasis of non-SLN. Gynecol Oncol (2020) 157(3):61923. Cervical injection is simpler, faster, and more effective, which is accepted and recognized as mandatory by worldwide gyn-oncologist in latest consensus and surgical assessment tool of SLNM in EC. Int J Clin Oncol (2017) 22(1):310. It is noted that, in the consensus, cervical injection is obligatory, whereas hysteroscopic or myometrial injection is not suggested. In NCCN guideline, pN0 (i+) is set for ITCs in EC patients (125). Int J Gynecol Cancer (2018) 28(1):13944. Bogani G, Mariani A, Paolini B, Ditto A, Raspagliesi F. Low-Volume Disease in Endometrial Cancer: The Role of Micrometastasis and Isolated Tumor Cells. A Prospective Study of Role of Sentinel Lymph Node Biopsy in Low-Risk/Intermediate-Risk Early-Stage Endometrial Carcinoma Using Dual-Dye and Dual-Site and Injection Technique. doi: 10.1136/ijgc-2020-002315, 62. Sentinel Lymph Node Mapping In Endometrial Cancer (SLNMIEC) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Lancet Oncol (2017) 18(3):38492. Persson J, Geppert B, Lonnerfors C, Bollino M, Masback A. Prospective Assessment of the Prevalence of Pelvic, Paraaortic and High Paraaortic Lymph Node Metastasis in Endometrial Cancer. The sentinel node procedure (also termed sentinel lymph node biopsy or SLNB) is the identification, removal and . Yabushita H, Shimazu M, Yamada H, Sawaguchi K, Noguchi M, Nakanishi M, et al. Brooks RA, Fleming GF, Lastra RR, Lee NK, Moroney JW, Son CH, et al. (130) hold that LVMD is more likely to be detected in low-risk patients. The Impact of the Type of Nodal Assessment on Prognosis in Patients With High-Intermediate and High-Risk ESMO/ESGO/ESTRO Group Endometrial Cancer. doi: 10.1007/s00432-018-2648-y, 43. Use of SPECT/CT for Improved Sentinel Lymph Node Localization in Endometrial Cancer. (18) followed up 643 EC patients and found that the incidence of lymphedema was related to the number of lymph nodes removed, the risk climbed to 50% when cutting more than 15 lymph nodes. doi: 10.1016/j.ejca.2019.04.025, 73. The sensitivity, NPV and FNR was 97.2%, 99.6%, and 2.8%. The results found that there was no statistical difference between the three strategies in DFS (p=0.570) and OS (p=0.911); moreover, the survival outcome was similar in low risk, intermediate risk, and high-risk group. doi: 10.1093/jnci/djn397, 14. doi: 10.17772/gp/2071, 146. Sentinel lymph node (SLN) mapping in endometrial cancer (EMCA) is rapidly gaining acceptance in the clinical community. Isolated para-aortic sentinel lymph nodes were detected in only 1% of patients in this study. Performance of Sentinel Lymph Node Biopsy in High-Risk Endometrial Cancer. In case of established cancerous dissemination it is postulated that the sentinel lymph nodes are the target organs primarily reached by metastasizing cancer cells from the tumor.. The reporting DR of subserosal injection varies from 73% to 95% (49). In addition, SLNM can improve the quality of life for patients by minimizing operation complications (7, 8). Gynecol Oncol (2013) 129(1):428. doi: 10.1007/s12253-019-00727-9, 148. Blue dye method, also known as bioactive dye tracing method, including methylene blue, isosulfur blue, and patent blue. However, it is noted that only a few intuitions perform SLN-algorithm only in the SLN cohort for the comparison study, whereas others are more likely to perform LAD followed by SLNM, thus, the results are rather a comparison between SLN+LAD and LAD, which make the survival results less convincing and more complicated. Sentinel Lymph Node Mapping in Gynecological Oncology. They found that SLN may improve the oncologic outcome with a more favorable 6-year OS (HR 0.5, 95% CI 0.3-0.8, p = 0.004) and PFS (HR 0.6, 95% CI 0.4-0.9, p = 0.03). doi: 10.1002/jso.25322, 151. doi: 10.1006/gyno.1996.0211, 31. It is a molecular-based method for the detection of metastatic lymph nodes in breast cancer or colorectal cancer patients using CK19 as a single marker. SLN mapping is a feasible and accurate alternative to stage patients with endometrial cancer. The sensitivity, FNR, and NPV was 84%, 2.4%, and 97%, respectively. The technique is autonomous and quantifiable, which saves pathologists work and makes results more comparable and less variable (151). Near-Infrared Fluorescence for Detection of Sentinel Lymph Nodes in Women With Cervical and Uterine Cancers (FILM): A Randomised, Phase 3, Multicentre, Non-Inferiority Trial. Surg Oncol (2018) 27(3):5149. J Surg Oncol (2021) 123(4):10928. doi: 10.1006/gyno.2000.6067, 140. On the contrary, it resulted in more complications in the high-risk histology type. Escalona S, Rezic M, Lpez C, Medina F, Jurado J, Lobo J. Ultra-Staging of the Sentinel Lymph Node in Endometrial Cancer. The recurrence rate of pelvic wall in SLNM + LAD group was lower (31% vs. 71%). Bodurtha etal. Buda A, Gasparri ML, Puppo A, Mereu L, De Ponti E, Di Martino G, et al. doi: 10.1016/j.ajog.2016.11.1033, 67. In 1977, Cabanas first used SLN lymphangiography in penile cancer (29). doi: 10.1016/j.ygyno.2008.05.016, 123. Also, SLN seemed to reduce the risk of recurrence in pelvis or lymph node region with a 6-year RFS of 95% compared to 90% (p=0.04) in LAD only group. But existing evidence shown that the incidence of IPL metastasis is rare with approximately 0.5% to 3.8% (49, 51). doi: 10.1016/j.ygyno.2017.09.030, 108. Ginekologia polska (2015) 86(4):2627. (Accessed June 03, 2021). Some scholars believe that routine HE staining is possible to miss LVMD in SLN, which could be identified by immunohistochemistry staining (IHC) and serial section, also known as ultra-staging, which is discussed in later paragraphs. 1. Researchers from Italy and Turkey suggest the addition of preoperative PET-CT in favor of PALAD decision (111, 113, 158). Cela et al reported 23 patients who underwent robotic-assisted surgery showing a 78.26% DR and 60.9% BDR (77). doi: 10.1016/j.ygyno.2014.03.019, 82. doi: 10.1245/s10434-016-5236-x, 36. Bogani G, Papadia A, Buda A, Casarin J, Di Donato V, Gasparri ML, et al. (84) applied two lymph node dissection methods to patients with low-risk EC in MSKCC and Mayo Clinic, respectively. Sentinel lymph node mapping has the potential to decrease morbidity and optimize the pathologic assessment of identified nodes in women with endometrial cancer. At present, the most commonly used strategy is SLAD according to Mayo Criteria proposed by Mariani etal. The aim of using this tool is to target the lymph nodes that are the most likely to be involved with metastatic cancer cells (sentinel lymph nodes) and thereby limit the extent of surgery needed and decrease surgical complications and long-term side effects associated . Gynecol Oncol (2013) 131(1):1038. Nemani D, Mitra N, Guo M, Lin L. Assessing the Effects of Lymphadenectomy and Radiation Therapy in Patients With Uterine Carcinosarcoma: A SEER Analysis. Introduction. Aetna considers the following experimental and investigational because the effectiveness of these approaches has not been established: Gynecol Oncol (2008) 111(1):828. J Cancer Res Clin Oncol (2020) 146(12):3199205. 81874108, 81802607, and 82072861), the Beijing Municipal Natural Science Foundation (grant 7202213), and National Key Technology R&D Program of China (grants 2019YFC1005200 and 2019YFC1005204). 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