David Cibula1, Roman Kocian2, Andrea Plaikner3, Jiri Jarkovsky4, Jaroslav Klat5, Ignacio Zapardiel6, Radovan Pilka7, Aureli Torne8, Borek Sehnal9, Marcela Ostojich10, Almerinda Petiz11, Octavio A Sanchez12, Jiri Presl13, Alessandro Buda14, Francesco Raspagliesi15, Peter Kascak16, Luc van Lonkhuijzen17, Marc Barahona18, Lubos Minar19, Pawel Blecharz20, Maja Pakiz21, Dariusz Wydra22, Leon C Snyman23, Kamil Zalewski24, Cristina Zorrero25, Pavel Havelka26, Mikulas Redecha27, Alla Vinnytska28, Ignace Vergote29, Solveig Tingulstad30, Martin Michal31, Barbara Kipp32, Jiri Slama2, Simone Marnitz33, Sylva Bajsova5, Alicia Hernandez6, Daniela Fischerova2, Kristyna Nemejcova34, Christhardt Kohler3. 1. Gynecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. Electronic address: david.cibula@vfn.cz. 2. Gynecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. 3. Department of Special Operative and Oncologic Gynaecology, Asklepios-Clinic Hamburg, Hamburg, Germany. 4. Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic. 5. Department of Obstetrics and Gynecology, University Hospital Ostrava, Ostrava Poruba, Czech Republic. 6. Gynecologic Oncology Unit, La Paz University Hospital, Madrid, Spain. 7. Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, Palacky University, University Hospital Olomouc, Olomouc, Czech Republic. 8. Unit of Gynecological Oncology, Institute Clinic of Gynaecology, Obstetrics, and Neonatology, Hospital Clinic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. 9. Department of Obstetrics and Gynecology, Bulovka Hospital, First Faculty of Medicine, Charles University, Prague, Czech Republic. 10. Department of Gynecology, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires Autonomous City, Argentina. 11. Department of Gynecology, Francisco Gentil Portuguese Oncology Institute, Porto, Portugal. 12. Department of Gynecologic Oncology, University Hospital of the Canary Islands, Las Palmas de Gran Canaria, Spain. 13. Department of Gynaecology and Obstetrics, University Hospital Pilsen, Charles University, Prague, Czech Republic. 14. Department of Obstetrics and Gynecology, Unit of Gynecologic Oncology Surgery, San Gerardo Hospital, Monza, Italy. 15. Fondazione IRCCS Istituto Nazionale Tumori - Milan, Milan, Italy. 16. Department of Obstetrics and Gynecology, Faculty Hospital Trencin, Trencin, Slovakia. 17. Center for Gynecologic Oncology, Amsterdam University Medical Center, Amsterdam, the Netherlands. 18. Department of Gynecology, University Hospital of Bellvitge, Biomedical Research Institute of Bellvitge, University of Barcelona, Barcelona, Spain. 19. Department of Gynecology and Obstetrics, Faculty of Medicine, Masaryk University, Brno, Czech Republic. 20. Department of Gynecologic Oncology, Centre of Oncology, M. Sklodowska-Curie Memorial Institute, Cracow Department, Cracow, Poland. 21. University Clinic for Gynaecology and Perinatology, University Medical Centre Maribor, Maribor, Slovenia. 22. Department of Gynecology, Gynecologic Oncology and Gynecologic Endocrinology, Medical University of Gdansk, Poland. 23. Gynaecologic Oncology Unit, Department of Obstetrics and Gynaecology, University of Pretoria, Pretoria, South Africa. 24. Department of Gynecologic Oncology, Holycross Cancer Center, Kielce, Poland. 25. Gynecology Department, Instituto Valenciano de Oncologia (IVO), Valencia, Spain. 26. Department of Obstetrics and Gynecology, KNTB a.s Zlin, Czech Republic. 27. Department of Gynaecology and Obstetrics, University Hospital, Comenius University, Bratislava, Slovakia. 28. LISOD - Israeli Oncological Hospital, Plyuty, Ukraine. 29. Department of Gynecology and Obstetrics, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium. 30. Department of Gynaecology, St Olav's Hospital, Trondheim, Norway. 31. Department of Obstetrics and Gynaecology, Hospital Ceske Budejovice, JSC, Ceske Budejovice, Czech Republic. 32. Department of Obstetrics and Gynecology, Cantonal Hospital of Lucerne, Lucerne, Switzerland. 33. Department of Radiation Oncology, CyberKnife and Radiotherapy University Hospital Cologne, Cologne, Germany. 34. Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Abstract
BACKGROUND: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. METHODS: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02494063). RESULTS: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. INTERPRETATION: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases.
BACKGROUND:SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. METHODS: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02494063). RESULTS: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. INTERPRETATION: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases.