Retrospective review of sentinel lymph node mapping in endometrial cancer using indocyanine green and near infra-red fluorescence imaging during minimally invasive surgery

Objectives: To determine the feasibility of sentinel lymph node (SLN) mapping in early-stage endometrial cancer and to evaluate the impact of the SLN result on adjuvant therapy prescription. Materials and methods: 140 women with histologically confirmed endometrial cancer, treated with a minimally invasive hysterectomy, bilateral salpingo-oophorectomy and SLN mapping were included. All mapped SLNs were confirmed by histopathology. Where the SLN was negative on H&E staining, ultra-staging with IHC was performed. Results: From January 2017 to May 2019, 122 patients were analysed. The overall and bilateral SLN detection rates were 86% (105/122) and 73% (89/122), respectively. The detection rates were not significantly different between low and high-risk disease. SLN metastasis was found in 15% (3/20) of patients the in high-risk group and 5.7% (5/87) in the low-risk group. Six of the 8 cases were identified by ultra-staging. Fourteen of 103 patients had their adjuvant treatment reduced based on SLN status after ultra-staging. Conclusion: SLN mapping can reliably detect the SLN in low and high-risk disease. The advantage for SLN mapping is in low-risk patients that allowed them to receive appropriate adjuvant therapy. Ultra-staging with IHC increased the detection of positive SLNs and decreased the prescribed adjuvant therapy in 14% of our patients.

Sentinel lymph node mapping; Endometrial cancer; Indocyanine green; Detec-tion; Ultra-staging; Adjuvant treatment

[1] Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. International Journal of Cancer. 2019; 144: 1941–1953.

[2] Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I. Endometrial cancer. Lancet. 2005; 366: 491–505.

[3] Chan JK, Cheung MK, Huh WK, Osann K, Husain A, Teng NN, et al. Therapeutic role of lymph node resection in endometrioid corpus cancer. Cancer. 2006; 107: 1823–1830.

[4] Lewin SN, Herzog TJ, Medel NIB, Deutsch I, Burke WM, Sun X, et al. Comparative performance of the 2009 international federation of gynecology and obstetrics’ staging system for uterine corpus cancer. Obstetrics & Gynecology. 2010; 116: 1141–1149.

[5] Clark TJ, Mann CH, Shah N, Khan KS, Song F, Gupta JK. Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: a systematic quantitative review. BJOG: An International Journal of Obstetrics and Gynaecology. 2002; 109: 313–321.

[6] Di Spiezio Sardo A, De Angelis MC, Della Corte L, Carugno J, Zizolfi B, Guadagno E, et al. Should endometrial biopsy under direct hysteroscopic visualization using the grasp technique become the new gold standard for the preoperative evaluation of the patient with endometrial cancer? Gynecologic Oncology. 2020; 158: 347–353.

[7] Amant F, Mirza MR, Koskas M, Creutzberg CL. Cancer of the corpus uteri. International Journal of Gynecology & Obstetrics. 2018; 143: 37–50.

[8] Panici PB, Basile S, Maneschi F, Lissoni AA, Signorelli M, Scambia G, et al. Systematic pelvic lymphadenectomy vs no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. Journal of the National Cancer Institute. 2008; 100: 1707–1716.

[9] Kitchener H, Swart AMC, Qian Q, Amos C, Parmar MKB. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet. 2009; 373: 125–136.

[10] Mariani A, Dowdy SC, Cliby WA, Gostout BS, Jones MB, Wilson TO, et al. Prospective assessment of lymphatic dissemination in endometrial cancer: a paradigm shift in surgical staging. Gynecologic Oncology. 2008; 109: 11–18.

[11] Nomura H, Aoki D, Suzuki N, Susumu N, Suzuki A, Tamada Y, et al. Analysis of clinicopathologic factors predicting paraaortic lymph node metastasis in endometrial cancer. International Journal of Gynecological Cancer. 2006; 16: 799–804.

[12] Kumar S, Podratz KC, Bakkum-Gamez JN, Dowdy SC, Wever AL, McGree ME, et al. Prospective assessment of prevalence of pelvic, paraaortic and high paraaortic lymph node metastasis in endometrial cancer. Gynecologic Oncology. 2014; 132: 38–43.

[13] Mariani A, Dowdy SC, Cliby WA, Haddock MG, Keeney GL, Lesnick TG, et al. Efficacy of systematic lymphadenectomy and adjuvant radiotherapy in node-positive endometrial cancer patients. Gynecologic Oncology. 2006; 10: 200–208.

[14] de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, et al. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multi-center, randomised, phase 3 trial. Lancet Oncology. 2018; 19: 295–309.

[15] Bohrer JC, Walters MD, Park A, Polston D, Barber MD. Pelvic nerve injury following gynecologic surgery: a prospective cohort study. American Journal of Obstetrics and Gynecology. 2009; 201:

531. e1–531.e7.

[16] Abu-Rustum NR, Alektiar K, Iasonos A, Lev G, Sonoda Y, Aghajanian C, et al. The incidence of symptomatic lower-extremity lymphedema following treatment of uterine corpus malignancies: a 12- year experience at Memorial Sloan-Kettering Cancer Center. Gynecologic Oncology. 2006; 103: 714–718.

[17] Frost JA, Webster KE, Bryant A, Morrison J. Lymphadenectomy for the management of endometrial cancer. Cochrane Database of Systematic Reviews. 2017; 10: CD007585.

[18] Bodurtha Smith AJ, Fader AN, Tanner EJ. Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis. American Journal of Obstetrics and Gynecology. 2017; 216: 459–476.e10.

[19] Holloway RW, Abu-Rustum NR, Backes FJ, Boggess JF, Gotlieb WH, Jeffrey Lowery W, et al. Sentinel lymph node mapping and staging in endometrial cancer: a society of gynecologic oncology literature review with consensus recommendations. Gynecologic Oncology. 2017; 146: 405–415.

[20] Barlin JN, Khoury-Collado F, Kim CH, Leitao MM, Chi DS, Sonoda Y, et al. The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes. Gynecologic Oncology. 2012; 125: 531–535.

[21] Edge SB, Compton CC. AJCC Cancer Staging Manual. 7th edn. New York: Springer. 2010.

[22] National Comprehensive Cancer Network. Uterine Neoplasm (Version 1.2021). 2021. Available at: https://www.nccn.org/pro fessionals/physician_gls/pdf/uterine.pdf (Accessed: 21 February 2021).

[23] Ianieri MM, Della Corte L, Campolo F, Cosentino F, Catena U, Bifulco G, et al. Indocyanine green in the surgical management of endometriosis: a systematic review. Acta Obstetricia et Gynecologica Scandinavica. 2021; 100: 189–199.

[24] Jewell EL, Huang JJ, Abu-Rustum NR, Gardner GJ, Brown CL, Sonoda Y, et al. Detection of sentinel lymph nodes in minimally invasive surgery using indocyanine green and near-infrared fluo-rescence imaging for uterine and cervical malignancies. Gynecologic Oncology. 2014; 133: 274–277.

[25] Papadia A, Imboden S, Siegenthaler F, Gasparri ML, Mohr S, Lanz S, et al. Laparoscopic indocyanine green sentinel lymph node mapping in endometrial cancer. Annals of Surgical Oncology. 2016; 23: 2206–2211.

[26] Buda A, Crivellaro C, Elisei F, Di Martino G, Guerra L, De Ponti E, et al. Impact of indocyanine green for sentinel lymph node mapping in early stage endometrial and cervical cancer: comparison with conventional radiotracer 99mTc and/or blue dye. Annals of Surgical Oncology. 2016; 23: 2183–2191.

[27] Plante M, Touhami O, Trinh X, Renaud M, Sebastianelli A, Grondin K, et al. Sentinel node mapping with indocyanine green and endoscopic near-infrared fluorescence imaging in endometrial cancer. a pilot study and review of the literature. Gynecologic Oncology. 2015; 137: 443–447.

[28] Rossi EC, Kowalski LD, Scalici J, Cantrell L, Schuler K, Hanna RK, et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncology. 2017; 18: 384–392.

[29] Hagen B, Valla M, Aune G, Ravlo M, Abusland AB, Araya E, et al. Indocyanine green fluorescence imaging of lymph nodes during robotic-assisted laparoscopic operation for endometrial cancer. a prospective validation study using a sentinel lymph node surgical algorithm. Gynecologic Oncology. 2016; 143: 479–483.

[30] Taşkın S, Şükür YE, Altın D, Ersöz CC, Turgay B, Kankaya D, et al. Laparoscopic near-infrared fluorescent imaging as an alternative option for sentinel lymph node mapping in endometrial cancer: a prospective study. International Journal of Surgery. 2017; 47: 13–17.

[31] Taşkın S, Sarı ME, Altın D, Ersöz CC, Gökçe A, Yüksel S, et al. Risk factors for failure of sentinel lymph node mapping using indocyanine green/near-infrared fluorescent imaging in endometrial cancer. Arch Gynecol Obstet. 2019; 299: 1667–1672.

[32] Touhami O, Grégoire J, Renaud M, Sebastianelli A, Plante M. Performance of sentinel lymph node (SLN) mapping in high-risk endometrial cancer. Gynecologic Oncology. 2017; 147: 549–553.

[33] Soliman PT, Westin SN, Dioun S, Sun CC, Euscher E, Munsell MF, et al. A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer. Gynecologic Oncology. 2017; 146: 234–239.

[34] Ehrisman J, Secord AA, Berchuck A, Lee PS, Di Santo N, Lopez-Acevedo M, et al. Performance of sentinel lymph node biopsy in high-risk endometrial cancer. Gynecologic Oncology Reports. 2016; 17: 69–71.