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CERVANTES: an international randomized trial of radical surgery followed by adjuvant (chemo) radiation versus no further treatment in patients with early-stage, intermediate-risk cervical cancer (CEEGOG-CX-05; ENGOT-CX16)
  1. David Cibula1,2,
  2. Martina Borčinová1,2,
  3. Roman Kocian1,2,
  4. David Feltl3,
  5. Sona Argalacsova3,
  6. Pavel Dvorak3,
  7. Daniela Fischerová2,3,
  8. Pavel Dundr2,4,
  9. Jiri Jarkovsky5,
  10. Eva Höschlová6,
  11. Jiri Slama1,2 and
  12. Giovanni Scambia7
  1. 1Gynaecologic Oncology Centre, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
  2. 2Central and Eastern European Gynecologic Oncology Group (CEEGOG), Prague, Czech Republic
  3. 3Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
  4. 4Department of Pathology, Charles University and General University Hospital in Prague, Prague, Czech Republic
  5. 5Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic
  6. 6Department of Psychology, Faculty of Arts, Charles University in Prague, Prague, Czech Republic
  7. 7Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
  1. Correspondence to Dr David Cibula, Gynaecologic Oncology Centre, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12000 Prague, Czech Republic; dc{at}davidcibula.cz

Abstract

Background The role of adjuvant treatment in the intermediate-risk group of patients with early-stage cervical cancer is controversial and is supported by a single randomized Gynecologic Oncology Group (GOG) 92 study performed more than 20 years ago. Recent retrospective studies have shown excellent local control in this group of patients after radical surgery with no additional adjuvant treatment.

Primary Objective To evaluate if adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with intermediate-risk cervical cancer.

Study Hypothesis Radical surgery alone is non-inferior to the combined treatment of radical surgery followed by adjuvant (chemo)radiation in disease-free survival in patients with intermediate-risk cervical cancer.

Trial Design This is a phase III, international, multicenter, randomized, non-inferiority trial in which patients with intermediate-risk cervical cancer will be randomized 1:1 into arm A, with no additional treatment after radical surgery, and arm B, receiving adjuvant external beam radiotherapy±brachytherapy ± concomitant chemotherapy. Patient data will be collected over 3 years post-randomization of the last enrolled patient for primary endpoint analysis or for 6 years for the overall survival analysis.

Major Inclusion/Exclusion Criteria Patients with intermediate-risk early-stage cervical cancer (IB1–IIA), defined as lymph node-negative patients with a combination of negative prognostic factors (tumor size >4 cm; tumor size >2 cm and lymphovascular space invasion; deep stromal invasion >2/3; or tumor-free distance <3 mm) with squamous cell carcinoma or human papillomavirus (HPV)-related adenocarcinoma, are eligible for the trial.

Primary Endpoint Disease-free survival defined as time from randomization to recurrence diagnosis.

Sample Size 514 patients from up to 90 sites will be randomized.

Estimated Dates for Completing Accrual and Presenting Results It is estimated that the accrual will be completed by 2027 (with 3 additional years of follow-up) and primary endpoint results will be published by 2031. Estimated trial completion is by 2034.

Trial Registration NCT04989647.

  • Cervical Cancer
  • Surgical Oncology
  • Radiotherapy

Data availability statement

Data are available upon request.

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Data availability statement

Data are available upon request.

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Footnotes

  • Contributors All authors planned, designed, and started the trial. DC is the trial chair and guarantor of the article. GS is the international deputy trial chair. JJ developed the statistical methods and is the trial statistician. DC and MB drafted the manuscript. All authors contributed to a critical review of the manuscript and approved the final version.

  • Funding This work was supported by grants from Charles University in Prague (COOPERATIO, UNCE 204065) and the Ministry of Health of the Czech Republic (MH CZ–DRO-VFN64165).

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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