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Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study
  1. Giuseppe Cucinella1,2,
  2. Gabriella Schivardi1,3,
  3. Xun Clare Zhou4,
  4. Mariam AlHilli5,
  5. Sumer Wallace6,
  6. Christoph Wohlmuth7,8,
  7. Glauco Baiocchi9,
  8. Nedim Tokgozoglu10,
  9. Francesco Raspagliesi11,
  10. Alessandro Buda12,13,
  11. Vanna Zanagnolo3,
  12. Ignacio Zapardiel14,
  13. Nisha Jagasia15,16,
  14. Robert Giuntoli17,
  15. Ariel Glickman18,
  16. Michele Peiretti19,
  17. Maximilian Lanner20,
  18. Enrique Chacon21,
  19. Julian Di Guilmi22,
  20. Augusto Pereira23,
  21. Enora Laas-Faron24,
  22. Ami Fishman25,
  23. Caroline C Nitschmann26,
  24. Katherine Kurnit27,
  25. Kristen Moriarty4,28,
  26. Amy Joehlin-Price5,
  27. Brittany Lees6,
  28. Allan Covens29,
  29. Louise De Brot9,
  30. Cagatay Taskiran30,31,
  31. Giorgio Bogani11,
  32. Fabio Landoni32,
  33. Tommaso Grassi33,
  34. Cristiana Paniga33,
  35. Francesco Multinu1,34,
  36. Luigi Antonio De Vitis1,34,
  37. Alicia Hernández34,
  38. Spyridon Mastroyannis17,
  39. Khaled Ghoniem1,
  40. Vito Chiantera35,
  41. Maryam Shahi36,
  42. Angela J Fought37,
  43. Michaela McGree37,
  44. Andrea Mariani1 and
  45. Gretchen Glaser1
  1. 1Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA
  2. 2Department of Surgical, Oncological, and Oral Sciences (DiChirOnS), University of Palermo, Palermo, Italy
  3. 3Department of Gynecology, European Institute of Oncology (IEO) IRCSS, Milano, Italy
  4. 4Hartford HealthCare, Hartford, Connecticut, USA
  5. 5Cleveland Clinic, Cleveland, Ohio, USA
  6. 6University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA
  7. 7Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  8. 8Department of Obstetrics and Gynecology, Paracelsus Medical University Salzburg, Salzburg, Austria
  9. 9Gynecologic Oncology, AC Camargo Cancer Center, Sao Paulo, Brazil
  10. 10Obstetrics and Gynecology, Turkish Society of Gynecologic Oncology, Istanbul, Turkey
  11. 11Foundation IRCCS National Cancer Institute, Milano, Italy
  12. 12University of Milan-Bicocca, Monza, Italy
  13. 13Ospedale Michele e Pietro Ferrero, Verduno, Italy
  14. 14Gynecologic Oncology, La Paz University Hospital, Madrid, Spain
  15. 15Queensland Centre for Gynaecological Cancer, Herston, Queensland, Australia
  16. 16Mater Adult Hospital, Brisbane, Queensland, Australia
  17. 17Division of Gynecologic Oncology, Penn Medicine, Philadelphia, Pennsylvania, USA
  18. 18Gynaecologic Oncology Unit, Hospital Clínic de Barcelona, Barcelona, Spain
  19. 19Department of Ob/GYN, University of Cagliari, Cagliari, Italy
  20. 20Department of Gynecology, Medical University of Graz, Graz, Steiermark, Austria
  21. 21Gynecologic Oncology, Universidad de Navarra, Pamplona, Navarra, Spain
  22. 22Gyn Onc, Hospital Britanico de Buenos Aires, Buenos Aires, Federal District, Argentina
  23. 23Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Comunidad de Madrid, Spain
  24. 24Chirurgie Senologique, Gynécologique et Reconstructrice, Curie Institute Hospital Group, Paris, France
  25. 25Obstetrics and Gynecology, Meir Medical Center, Kfar-Saba, Israel
  26. 26Lahey Clinic Medical Center, Burlington, Massachusetts, USA
  27. 27Obstetrics and Gynecology, University of Chicago Biological Sciences Division, Chicago, Illinois, USA
  28. 28Obstetrics and Gynecology Residency Program, University of Connecticut, Storrs, Connecticut, USA
  29. 29University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  30. 30Turkish Society of Gynecologic Oncology, Istanbul, Turkey
  31. 31Department of Gynecologic Oncology, Koc University School of Medicine, Istanbul, Turkey
  32. 32Clinic of Obstetrics and Gynecology, San Gerardo Hospital, Monza, University of Milan-Bicocca Department of Medicine and Surgery, Monza, Lombardia, Italy
  33. 33San Gerardo Hospital; University of Milan-Bicocca, Monza, Italy
  34. 34Gynecologic Oncology, European Institute of Oncology (IEO) IRCSS, Milan, Italy
  35. 35Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
  36. 36Department of Pathology, Mayo Clinic, Rochester, Minnesota, USA
  37. 37Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Dr Gretchen Glaser, Department of Obstetrics and Gynecology, Mayo Clinic, 200 First Street SW Rochester, Minnesota, 55905, USA; glaser.gretchen{at}mayo.edu

Abstract

Objective The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients.

Methods Patients with SLNs–isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan–Meier methods.

Results 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs–isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1–3.0) and 2.6 years (IQR 0.6–4.2) in the SLN–isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN–isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion.

Conclusions Patients with SLNs–isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs–isolated tumor cells was not associated with worse overall survival.

  • Endometrial Neoplasms
  • Sentinel Lymph Node
  • Lymphatic Metastasis
  • Lymph Nodes
  • Uterine Cancer

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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Footnotes

  • Twitter @Cucinella_G, @glaucobaiocchi, @Quique_ChC, @TommasoGrassi3, @Fmultinu, @LuigiDEvitis, @KhaledGhoniemMD

  • Contributors Conception of the study: AM, GG, and GC. Methodology and investigation: AM, GG, and GC. Dataset preparations (software) and variables revision: GC, GS, MM, and AJF. Data collection and interpretation individually by each center (resources): GC, GS, XCZ, KM, MA, AJ-P, SW, BL, CW, AC, GB, LDB, NT, CT, FR, AB, CP, TG, FL, VZ, FM, LADV, IZ, AH, NJ, RG, SM, AG, MP, ML, EC, JDG, AP, EL-F, AF, CCN, VC, and KG. Data validation and curation: GC and MM. Formal statistical analysis: MM and AJF. Writing-original draft: GC, GG, AM, MEM, and AJF. Writing-review and editing: all authors. Supervision: AM and GG. Project administration: all authors. Final approval of manuscript: all authors. Guarantor: AM and GG.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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