BACKGROUND: This is a multicentre, European, prospective trial evaluating the diagnostic accuracy of One Step Nucleic Acid Amplification (OSNA) compared to sentinel lymph nodes histopathological ultrastaging in endometrial cancer patients. METHODS: Centres with expertise in sentinel lymph node mapping in endometrial cancer patients in Europe will be invited to participate in the study. Participating units will be trained on the correct usage of the OSNA RD-210 analyser and nucleic acid amplification reagent kit LYNOAMP CK19 E for rapid detection of metastatic nodal involvement, based on the cytokeratin 19 (CK19) mRNA detection. Endometrial cancer patients ≥ 18 years listed for surgical treatment with sentinel lymph node mapping, with no history of other types of cancer and who provide a valid written consent will be considered potentially eligible for the study. However, they will only be enrolled if a successful sentinel lymph node mapping is retrieved. Each node will be processed according to the study protocol and assessed by both OSNA and ultrastaging. DISCUSSION: The accuracy of OSNA (index test) will be assessed against sentinel lymph node histopathological ultrastaging (reference test). This European study has the potential to be the largest study on the use of OSNA in endometrial cancer to date. OSNA could represent a modern diagnostic alternative to sentinel lymph node ultrastaging with the added benefits of standardisation and fast results. TRIAL REGISTRATION: The study was registered in the German Clinical Trial Register - Nr. DRKS00021520, registration date 25th of May 2020, URL of the trial registry record: https://drks.de/search/en/trial/DRKS00021520 .

Department of Biology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Gynaecology and Obstetrics University Hospital Pilsen Charles University Pilsen Czech Republic

Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Sikl´s Department of Pathology University Hospital Pilsen Charles University Pilsen Czech Republic

Sysmex Europe Bornbach 1 22848 Norderstedt Germany

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GLOBOCAN. Estimated number of new cases in 2020, corpus uteri, females, all ages.2021(23.3.2021): https://gco.iarc.fr/today/online-analysis-table?v=2020&mode=population&mode_population=who&population=900&populations=900&key=asr&sex=2&cancer=24&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&include_nmsc=1&include_nmsc_other=1.

Van den Bosch T, Coosemans A, Morina M, Timmerman D, Amant F. Screening for uterine tumours. Best Pract Res Clin Obstet Gynaecol. 2012;26(2):257–66. PubMed

Kwon JS, Scott JL, Gilks CB, Daniels MS, Sun CC, Lu KH. Testing women with endometrial cancer to detect Lynch syndrome. J Clin Oncology: Official J Am Soc Clin Oncol. 2011;29(16):2247–52. PubMed PMC

Hoang LN, Kinloch MA, Leo JM, Grondin K, Lee CH, Ewanowich C, et al. Interobserver Agreement in Endometrial Carcinoma Histotype diagnosis varies depending on the Cancer Genome Atlas (TCGA)-based Molecular Subgroup. Am J Surg Pathol. 2017;41(2):245–52. PubMed

Colombo N, Creutzberg C, Amant F, Bosse T, Gonzalez-Martin A, Ledermann J, et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-updagger. Ann Oncol. 2016;27(1):16–41. PubMed

Nadeem R, Abu-Rustum CMY, Rebeca Arend E, Barber K, Bradley, et al. NCCN Guidelines, Uterine neoplasms, Version 1.2023. National Comprehensive Cancer Network; 2023. PubMed

Rossi EC, Kowalski LD, Scalici J, Cantrell L, Schuler K, Hanna RK, et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol. 2017;18(3):384–92. PubMed

Bodurtha Smith AJ, Fader AN, Tanner EJ. Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis. Am J Obstet Gynecol. 2017;216(5):459–76. e10. PubMed

Guidelines N, Uterine Neoplasms. NCCN Clinical Practice Guidelines in Oncology Version 1.2021-October 20,2020;2022(20.10.2022):http://www.nccn.org/patients

Holloway RW, Abu-Rustum NR, Backes FJ, Boggess JF, Gotlieb WH, Jeffrey Lowery W, et al. Sentinel lymph node mapping and staging in endometrial cancer: a Society of Gynecologic Oncology literature review with consensus recommendations. Gynecol Oncol. 2017;146(2):405–15. PubMed PMC

Soliman PT, Frumovitz M, Spannuth W, Greer MJ, Sharma S, Schmeler KM, et al. Lymphadenectomy during endometrial cancer staging: practice patterns among gynecologic oncologists. Gynecol Oncol. 2010;119(2):291–4. PubMed PMC

Sinno AK, Peijnenburg E, Fader AN, Temkin SM, Stone R, Levinson K, et al. Reducing overtreatment: a comparison of lymph node assessment strategies for endometrial cancer. Gynecol Oncol. 2016;143(2):281–6. PubMed

Cormier B, Rozenholc AT, Gotlieb W, Plante M, Giede C, Communities of Practice Group of Society of Gynecologic Oncology of C. Sentinel lymph node procedure in endometrial cancer: a systematic review and proposal for standardization of future research. Gynecol Oncol. 2015;138(2):478–85. PubMed

Colombo N, Creutzberg C, Amant F, Bosse T, Gonzalez-Martin A, Ledermann J, et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up. Int J Gynecol cancer: Official J Int Gynecol Cancer Soc. 2016;26(1):2–30. PubMed PMC

Santaballa A, Matias-Guiu X, Redondo A, Carballo N, Gil M, Gomez C, et al. SEOM clinical guidelines for endometrial cancer (2017). Clin Transl Oncol. 2018;20(1):29–37. PubMed PMC

Berek JS, Matias-Guiu X, Creutzberg C, Fotopoulou C, Gaffney D, Kehoe S, et al. FIGO staging of endometrial cancer: 2023. Int J Gynaecol Obstet. 2023;162(2):383–94. PubMed

Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, et al. Uterine neoplasms, Version 1.2018, NCCN Clinical Practice guidelines in Oncology. J Natl Compr Cancer Network: JNCCN. 2018;16(2):170–99. PubMed

Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer staging Manual: continuing to build a bridge from a population-based to a more personalized approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9. PubMed

Shimazu K, Miyake T, Okuno J, Naoi Y, Tanei T, Shimoda M, et al. One-step nucleic acid amplification can identify Sentinel Node-negative breast Cancer patients with excellent prognosis. Anticancer Res. 2019;39(3):1447–54. PubMed

Marhic A, Tremblay JF, Kaci R, André T, Eveno C, Pocard M. Molecular analysis of sentinel lymph node in colon carcinomas by one-step nucleic acid amplification (OSNA) reduces time to adjuvant chemotherapy interval. Dig Liver Disease: Official J Italian Soc Gastroenterol Italian Association Study Liver. 2017;49(8):924–8. PubMed

Croner RS, Geppert CI, Bader FG, Nitsche U, Spath C, Rosenberg R, et al. Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study. Br J Cancer. 2014;110(10):2544–50. PubMed PMC

Fanfani F, Monterossi G, Di Meo ML, La Fera E, Dell’Orto F, Gioe A, et al. Standard ultra-staging compared to one-step nucleic acid amplification for the detection of sentinel lymph node metastasis in endometrial cancer patients: a retrospective cohort comparison. Int J Gynecol cancer: Official J Int Gynecol Cancer Soc. 2020;30(3):372–7. PubMed

Kostun J, Pesta M, Slama J, Slunecko R, Vlasak P, Bouda J, et al. One-step nucleic acid amplification vs ultrastaging in the detection of sentinel lymph node metastasis in endometrial cancer patients. J Surg Oncol. 2019;119(3):361–9. PubMed

Bizzarri N, Pedone Anchora L, Zannoni GF, Santoro A, Valente M, Inzani F, et al. Role of one-step nucleic acid amplification (OSNA) to detect sentinel lymph node low-volume metastasis in early-stage cervical cancer. Int J Gynecol cancer: Official J Int Gynecol Cancer Soc. 2020;30(3):364–71. PubMed

Ruscito I, Gasparri ML, Braicu EI, Bellati F, Raio L, Sehouli J, et al. Sentinel Node Mapping in Cervical and Endometrial Cancer: Indocyanine Green Versus Other Conventional Dyes-A Meta-analysis. Ann Surg Oncol. 2016;23(11):3749–56. PubMed

Cibula D, McCluggage WG. Sentinel lymph node (SLN) concept in cervical cancer: current limitations and unanswered questions. Gynecol Oncol. 2019;152(1):202–7. PubMed

Slama J, Dundr P, Dusek L, Cibula D. High false negative rate of frozen section examination of sentinel lymph nodes in patients with cervical cancer. Gynecol Oncol. 2013;129(2):384–8. PubMed

Milam MR, Java J, Walker JL, Metzinger DS, Parker LP, Coleman RL. Nodal metastasis risk in endometrioid endometrial cancer. Obstet Gynecol. 2012;119(2 Pt 1):286–92. PubMed PMC

Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL et al. Carcinoma of the corpus uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2006;95 Suppl 1:S105-43. PubMed

Fanfani F, Monterossi G, Ghizzoni V, Rossi ED, Dinoi G, Inzani F, et al. One-step nucleic acid amplification (OSNA): a fast molecular test based on CK19 mRNA concentration for assessment of lymph-nodes metastases in early stage endometrial cancer. PLoS ONE. 2018;13(4):e0195877. PubMed PMC

Lopez-Ruiz ME, Diestro MD, Yebenes L, Berjon A, Diaz de la Noval B, Mendiola M, et al. One-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node metastasis in endometrial cancer. Gynecol Oncol. 2016;143(1):54–9. PubMed

Nagai T, Niikura H, Okamoto S, Nakabayashi K, Matoda M, Utsunomiya H, et al. A new diagnostic method for rapid detection of lymph node metastases using a one-step nucleic acid amplification (OSNA) assay in endometrial cancer. Ann Surg Oncol. 2015;22(3):980–6. PubMed

Raffone A, Travaglino A, Santoro A, Esposito I, Angelico G, Spadola S, et al. Accuracy of one-step nucleic acid amplification in detecting Lymph Node metastases in Endometrial Cancer. Pathol Oncol Res. 2020;26(4):2049–56. PubMed

Diestro MD, Berjon A, Zapardiel I, Yebenes L, Ruiz I, Lekuona A, et al. One-step nucleic acid amplification (OSNA) of Sentinel Lymph Node in Early-Stage Endometrial Cancer: Spanish Multicenter Study (ENDO-OSNA). Cancers. 2021;13:17. PubMed PMC

La Fera E, Bizzarri N, Petrecca A, Monterossi G, Dinoi G, Zannoni GF, et al. Evaluation of the one-step nucleic acid amplification method for rapid detection of lymph node metastases in endometrial cancer: prospective, multicenter, comparative study. Int J Gynecol cancer: Official J Int Gynecol Cancer Soc. 2023;33(7):1063–9. PubMed

Togami S, Tanimoto A, Yanazume S, Tokunaga H, Nagai T, Watanabe M, et al. Evaluation of the one-step nucleic acid amplification assay for detecting lymph node metastasis in patients with cervical and endometrial cancer: a multicenter prospective study. Gynecol Oncol. 2023;170:70–6. PubMed

Saruta Y, Puig-Junoy J. Cost and Budget Impact Analysis of an Accurate Intraoperative Sentinel Lymph Node diagnosis for breast Cancer metastasis. Appl Health Econ Health Policy. 2016;14(3):323–35. PubMed

Raia-Barjat T, Trombert B, Khaddage A, Douchet C, Seffert P, Peoc’h M, et al. OSNA (one-step nucleic acid amplification) sentinel lymph node intraoperative molecular analysis in breast cancer: a cost-benefit analysis. Med Oncol (Northwood Lond Engl). 2014;31(12):322. PubMed