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)

Abstract

BackgroundThe 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 ObjectiveTo evaluate if adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with intermediate-risk cervical cancer.Study HypothesisRadical 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 DesignThis 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 CriteriaPatients 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 EndpointDisease-free survival defined as time from randomization to recurrence diagnosis.Sample Size514 patients from up to 90 sites will be randomized.Estimated Dates for Completing Accrual and Presenting ResultsIt 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 RegistrationNCT04989647.

Evaluation of Surgical Approaches and Use of Adjuvant Radiotherapy with Respect to Oncologic Outcomes in the Management of Clinically Early-Stage Cervical Carcinoma

“…Some have suggested de-escalation of treatment for patients who meet Sedlis criteria, with improved surgical techniques compared to when Sedlis was originally published, and advocate for a personalized approach [ 24 ] and the excellent outcomes herein may support this. This is being investigated in the CERVANTES study currently [ 25 ] and may allow for de-escalation in these patients.…”

Interviews conducted at the European Society of Gynaecological Oncology 2022 Congress: a ENYGO-IJGC Fellows initiative

“…Professor Cibula strongly believes in the SLN concept in view of the step-by-step lymphatic spread of cervical cancer, also recently demonstrated by the results of the SENTIX study 17. Regarding radical hysterectomy, “the new challenge is represented by the role of radical surgery alone in the ‘intermediate-risk’ disease and the ongoing CERVANTES trial18 is aiming to assess the role of adjuvant (chemo)radiotherapy in this setting”, he stated. “We are also awaiting the results of the SHAPE trial to understand the role of radical surgery in low risk disease”, he added.…”

Can we improve survival with less overall morbidity for patients with intermediate-risk cervical cancer without the use of external beam radiotherapy?

“…The CERVANTES trial is currently evaluating the therapeutic impact of adjuvant external beam radiotherapy (±brachytherapy and ±concomitant chemotherapy) in an intermediate-risk group randomized 1:1 between surgery only (arm A) and surgery followed by external beam radiotherapy (arm B) in a non-inferiority design with disease-free survival as the primary endpoint 3. The sample size should yield a power of 80% to detect a non-inferiority margin of 5%, assuming 2-year disease-free survival for arm B of 85%.…”