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Sentinel lymph node biopsy without systematic pelvic lymphadenectomy in females with early-stage cervical cancer: final outcome of the SENTIX prospective, single-arm, noninferiority, international trial

Nature Cancer volume 6, pages 1585–1594 (2025)Cite this article

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Abstract

Sentinel lymph node (SLN) biopsy with ultrastaging is standard in endometrial and vulvar cancers, whereas systematic pelvic lymphadenectomy (PLND) remains recommended in cervical cancer. The SENTIX trial prospectively evaluated the safety of SLN biopsy without PLND in early-stage cervical cancer. Female patients, International Federation of Gynaecology and Obstetrics 2018 stage IA1/LVSI+ to IB2 disease, were enrolled between 2016 and 2020 across 47 sites in 18 countries. All underwent SLN biopsy followed by hysterectomy/trachelectomy. Patients with undetected, unilateral or intraoperatively metastatic SLNs were excluded from the intention-to-treat cohort. SLNs were assessed by pathological ultrastaging. Of 731 patients enrolled, 594 formed the intention-to-treat cohort. SLN metastases were identified in 82 patients (12%), 56.1% intraoperatively and 43.9% by ultrastaging. At 2 years, the recurrence rate was 6.1% (one-sided 95% CI 7.9%), confirming noninferiority to the 7% reference rate. Two-year disease-free and overall survival rates were 93.3% (95% CI 94.9–91.6) and 97.9% (95% CI 98.9–97.0), respectively. Here we show that SLN biopsy without systematic PLND did not increase the risk of recurrence in patients with early-stage cervical cancer. Pathological ultrastaging of SLNs detected about 44% of N1 cases, which would be missed by a standard lymph node assessment. Trial registration: ClinicalTrials.gov (NCT02494063).

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Fig. 1: Patient flowchart.
Fig. 2: Survival outcomes according to the surgical approach.
Fig. 3: Survival outcomes according to the surgical approach.
Fig. 4: Disease-free survival according to the surgical approach in per-protocol population.
Fig. 5: Kaplan–Meier curves for disease-free survival according to risk.

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Data availability

The data that support the findings of this study are provided within the article and its supplementary materials. Patient-sensitive data that are subject to privacy regulations are available from the corresponding author upon reasonable request. Source data are provided with this paper.

References

  1. Oonk, M. H. et al. Size of sentinel-node metastasis and chances of non-sentinel-node involvement and survival in early stage vulvar cancer: results from GROINSS-V, a multicentre observational study. Lancet Oncol. 11, 646–652 (2010).

    Article  PubMed  Google Scholar 

  2. Ballester, M. et al. Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO). Lancet Oncol. 12, 469–476 (2011).

    Article  PubMed  Google Scholar 

  3. Cusimano, M. C. et al. Assessment of sentinel lymph node biopsy vs lymphadenectomy for intermediate- and high-grade endometrial cancer staging. JAMA Surg. 156, 157–164 (2021).

    Article  PubMed  Google Scholar 

  4. Rossi, E. C. et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol. 18, 384–392 (2017).

    Article  PubMed  Google Scholar 

  5. Soliman, P. T. et al. A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer. Gynecol. Oncol. 146, 234–239 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), Cervical Cancer. Version 2.2024. https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf (2024).

  7. Cibula, D. et al. The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology guidelines for the management of patients with cervical cancer. Int. J. Gynecol. Cancer 28, 641–655 (2018).

    Article  PubMed  Google Scholar 

  8. Cibula, D. et al. ESGO/ESTRO/ESP guidelines for the management of patients with cervical cancer - update 2023. Int. J. Gynecol. Cancer 33, 649–666 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Margioula-Siarkou, C. et al. Sentinel lymph node staging in early-stage cervical cancer: a comprehensive review. J. Clin. Med. https://doi.org/10.3390/jcm13010027 (2023).

  10. Ronsini, C. et al. The oncological implication of sentinel lymph node in early cervical cancer: a meta-analysis of oncological outcomes and type of recurrences. Medicina https://doi.org/10.3390/medicina58111539 (2022).

  11. Dundr, P. et al. Pathologic protocols for sentinel lymph nodes ultrastaging in cervical cancer. Arch. Pathol. Lab. Med. https://doi.org/10.5858/arpa.2019-0249-RA (2019).

  12. Mauro, J. et al. Survival after sentinel node biopsy alone in early-stage cervical cancer: a systematic review. Int. J. Gynecol. Cancer 33, 1370–1375 (2023).

    Article  PubMed  Google Scholar 

  13. Cibula, D. et al. The annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer. Eur. J. Cancer 158, 111–122 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Chiva, L. SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer. Int. J. Gynecol. Cancer 30, 449–450 (2020).

    Article  Google Scholar 

  15. Mathevet, P. et al. Sentinel lymph node biopsy and morbidity outcomes in early cervical cancer: results of a multicentre randomised trial (SENTICOL-2). Eur. J. Cancer 148, 307–315 (2021).

    Article  PubMed  Google Scholar 

  16. Ramirez, P. T. et al. Minimally invasive versus abdominal radical hysterectomy for cervical cancer. New Engl. J. Med. 379, 1895–1904 (2018).

    Article  PubMed  Google Scholar 

  17. Plante, M. et al. Simple versus radical hysterectomy in women with low-risk cervical cancer. New Engl. J. Med. 390, 819–829 (2024).

    Article  PubMed  Google Scholar 

  18. Schmeler, K. M. et al. ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer. Int. J. Gynecol. Cancer 31, 1317–1325 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kocian, R. et al. Sentinel lymph node pathological ultrastaging: final outcome of the SENTIX prospective international study in patients with early-stage cervical cancer. Gynecol. Oncol. 188, 83–89 (2024).

    Article  PubMed  Google Scholar 

  20. Lecuru, F. R. et al. SENTICOL III: an international validation study of sentinel node biopsy in early cervical cancer. A GINECO, ENGOT, GCIG and multicenter study. Int. J. Gynecol. Cancer 29, 829–834 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Tu, H. et al. Sentinel lymph node biopsy versus pelvic lymphadenectomy in early-stage cervical cancer: a multi-center randomized trial (PHENIX/CSEM 010). Int. J. Gynecol. Cancer 30, 1829–1833 (2020).

    Article  PubMed  Google Scholar 

  22. Vergote, I. et al. European Network of Gynaecological Oncological Trial Groups’ requirements for trials between academic groups and pharmaceutical companies. Int. J. Gynecol. Cancer 20, 476–478 (2010).

    Article  PubMed  Google Scholar 

  23. Cibula, D. et al. A prospective multicenter trial on sentinel lymph node biopsy in patients with early-stage cervical cancer (SENTIX). Int. J. Gynecol. Cancer 29, 212–215 (2019).

    Article  PubMed  Google Scholar 

  24. Cibula, D. et al. Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: the SENTIX trial. Eur. J. Cancer 137, 69–80 (2020).

    Article  PubMed  Google Scholar 

  25. Pecorelli, S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int. J. Gynaecol. Obstet. 105, 103–104 (2009).

    Article  PubMed  Google Scholar 

  26. Querleu, D., Cibula, D. & Abu-Rustum, N. R. 2017 update on the Querleu-Morrow classification of radical hysterectomy. Ann. Surg. Oncol. 24, 3406–3412 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Nemejcova, K. et al. Central pathology review in SENTIX, a prospective observational international study on sentinel lymph node biopsy in patients with early-stage cervical cancer (ENGOT-CX2). Cancers https://doi.org/10.3390/cancers12051115 (2020).

  28. Borčinová, M. et al. Challenges in lower limb lymphoedema assessment based on limb volume change: lessons learnt from the SENTIX prospective multicentre study. Gynecol. Oncol. 164, 76–84 (2022).

    Article  PubMed  Google Scholar 

  29. Zapardiel, I. et al. Voiding recovery after radical parametrectomy in cervical cancer patients: an international prospective multicentre trial - SENTIX. Gynecol. Oncol. 160, 729–734 (2021).

    Article  PubMed  Google Scholar 

  30. Cibula, D. et al. Bilateral ultrastaging of sentinel lymph node in cervical cancer: lowering the false-negative rate and improving the detection of micrometastasis. Gynecol. Oncol. 127, 462–466 (2012).

    Article  PubMed  Google Scholar 

  31. Cibula, D. et al. Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer. Gynecol. Oncol. 124, 496–501 (2012).

    Article  CAS  PubMed  Google Scholar 

  32. Ayhan, A. et al. Prognostic factors in FIGO stage IB cervical cancer without lymph node metastasis and the role of adjuvant radiotherapy after radical hysterectomy. Int. J. Gynecol. Cancer 14, 286–292 (2004).

    Article  CAS  PubMed  Google Scholar 

  33. Bodurka-Bevers, D. et al. Posttherapy surveillance of women with cervical cancer: an outcomes analysis. Gynecol. Oncol. 78, 187–193 (2000).

    Article  CAS  PubMed  Google Scholar 

  34. Chittithaworn, S., Hanprasertpong, J., Tungsinmunkong, K. & Geater, A. Association between prognostic factors and disease-free survival of cervical cancer stage IB1 patients undergoing radical hysterectomy. Asian Pac. J. Cancer Prev. 8, 530–534 (2007).

    PubMed  Google Scholar 

  35. Hoogendam, J. P., Verheijen, R. H., Wegner, I. & Zweemer, R. P. Oncological outcome and long-term complications in robot-assisted radical surgery for early stage cervical cancer: an observational cohort study. BJOG 121, 1538–1545 (2014).

    Article  CAS  PubMed  Google Scholar 

  36. Landoni, F. et al. Class II versus class III radical hysterectomy in stage IB-IIA cervical cancer: a prospective randomized study. Gynecol. Oncol. 80, 3–12 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. Laterza, R. M. et al. Recurrence of early stage cervical cancer after laparoscopic versus open radical surgery. Int. J. Gynecol. Cancer 26, 547–552 (2016).

    Article  PubMed  Google Scholar 

  38. Lee, C. L., Wu, K. Y., Huang, K. G., Lee, P. S. & Yen, C. F. Long-term survival outcomes of laparoscopically assisted radical hysterectomy in treating early-stage cervical cancer. Am. J. Obstet. Gynecol. 203, 165.e161–167 (2010).

    Article  Google Scholar 

  39. Lim, K. C., Howells, R. E. & Evans, A. S. The role of clinical follow up in early stage cervical cancer in South Wales. BJOG 111, 1444–1448 (2004).

    Article  CAS  PubMed  Google Scholar 

  40. Park, J. Y. et al. Outcomes after radical hysterectomy in patients with early-stage adenocarcinoma of uterine cervix. Br. J. Cancer 102, 1692–1698 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Park, N. Y. et al. Oncologic results and surgical morbidity of laparoscopic nerve-sparing radical hysterectomy in the treatment of FIGO stage IB cervical cancer: long-term follow-up. Int. J. Gynecol. Cancer 21, 355–362 (2011).

    Article  PubMed  Google Scholar 

  42. Sartori, E. et al. Early stage cervical cancer: adjuvant treatment in negative lymph node cases. Gynecol. Oncol. 107, S170–S174 (2007).

    Article  PubMed  Google Scholar 

  43. Togami, S., Kamio, M., Yanazume, S., Yoshinaga, M. & Douchi, T. Can pelvic lymphadenectomy be omitted in stage IA2 to IIB uterine cervical cancer? Int. J. Gynecol. Cancer 24, 1072–1076 (2014).

    Article  PubMed  Google Scholar 

  44. Zanagnolo, V. et al. Clinical and oncologic outcomes of robotic versus abdominal radical hysterectomy for women with cervical cancer: experience at a referral cancer center. Int. J. Gynecol. Cancer 26, 568–574 (2016).

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the Czech Health Research Council (NV19-03-00023; no. 16-31643A), Charles University in Prague (UNCE/24/MED/018, UNCE/MED/008 and PROGRES Q28/LF1) and the Charles University Research program (Cooperatio – Maternal and Childhood Care, Neonatology) and by an institutional grant from the General University Hospital in Prague (CZ-DRO-VFN64165). The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. We acknowledge the investigators from all 47 sites participating in the SENTIX trial. We also thank all the medical specialists, data and case managers, secretaries, study coordinators and other people involved in the SENTIX trial. We also acknowledge the support of N. D. Smith (Freelance Medical Writer, Auckland, New Zealand) for providing English-language editorial support in the preparation of this article under guidance from the authors.

Author information

Authors and Affiliations

  1. Gynecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    David Cibula, Roman Kocián, Jiří Sláma & Daniela Fischerová

  2. Radiation Oncology Vosspalais, Berlin, Germany

    Simone Marnitz

  3. Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic

    Jiří Jarkovský

  4. Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic

    Pavel Dundr & Kristyna Nemejcova

  5. University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic

    Jaroslav Klát

  6. Gynecologic Oncology Unit, La Paz University Hospital, Madrid, Spain

    Ignacio Zapardiel

  7. Unit Gynecology Oncology, Hospital Universitario Materno Infantil de Canarias, Las Palmas, Spain

    Octavio Arencibia

  8. UNIMIB-IRCCS-San Gerardo Monza, Monza, Italy

    Fabio Landoni

  9. Department of Gynecology and Obstetrics, University Hospital Pilsen, Charles University Faculty of Medicine in Pilsen, Pilsen, Czech Republic

    Jiri Presl

  10. Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

    Francesco Raspagliesi

  11. Department of Gynecology and Obstetrics, Bulovka University Hospital and Charles University – First Faculty of Medicine, Prague, Czech Republic

    Michal Zikán

  12. Center for Gynecologic Oncology Amsterdam, Amsterdam University Medical Centers, Cancer Center Amsterdam, Amsterdam, The Netherlands

    Luc RCW van Lonkhuijzen

  13. Gynecologic Oncology Unit, Institute Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    Aureli Torne

  14. Department of Gynecology and Obstetrics, University Hospital Brno and Masaryk University, Brno, Czech Republic

    Lubos Minar

  15. Institute of Oncology Angel H. Roffo, Buenos Aires, Argentina

    Marcela Ostojich

  16. University Hospital Olomouc, Palacky University Olomouc, Olomouc, Czech Republic

    Radovan Pilka

  17. Department of Gynecology, Francisco Gentil Portuguese Oncology Institute, Porto, Portugal

    Almerinda Ferreira Petiz

  18. Eviamed, Outpatient Diagnostic & Surgery Center Berlin – Charlottenburg, Berlin, Germany

    Anja Petzel

  19. Department of Radiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    Andrea Burgetová

  20. Department of Gynecology, Asklepios Clinic Hamburg Altona; Department of Gynecology, DRK Klinik Berlin Westend, Berlin, Germany

    Christhardt Köhler

Authors
  1. David Cibula
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Contributions

Conception: D.C. and R.K. Data curation: D.C. and R.K. Formal analysis: J.J. and D.C. Funding acquisition: D.C. Investigation: D.C., S.M., R.K., P.D., J.K., I.Z., O.A., F.L., J.P., F.R., M.Z., L.R.C.W.v.L., A.T., J.S., L.M., M.O., R.P., A.F.P., A.P., A.B., K.N., D.F. and C.K. Methodology: D.C., R.K., P.D., A.B. and D.F. Project administration: D.C. and R.K. Validation: D.C., R.K., J.J., P.D. and K.N. Writing – original draft: D.C. Writing – review and editing: All authors. Accountable for all aspects of the work: All authors.

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Correspondence to David Cibula.

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Cibula, D., Marnitz, S., Jarkovský, J. et al. Sentinel lymph node biopsy without systematic pelvic lymphadenectomy in females with early-stage cervical cancer: final outcome of the SENTIX prospective, single-arm, noninferiority, international trial. Nat Cancer 6, 1585–1594 (2025). https://doi.org/10.1038/s43018-025-01016-y

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