Surgical versus clinical staging prior to primary chemoradiation in patients with cervical cancer FIGO stages IIB–IVA: oncologic results of a prospective randomized international multicenter (Uterus-11) intergroup study

Abstract

ObjectiveRevised staging of patients with locally advanced cervical cancer is based on clinical examination, imaging, and potential surgical findings. A known limitation of imaging techniques is an appreciable rate of understaging. In contrast, surgical staging may provide more accurate information on lymph node involvement. The aim of this prospective study was to evaluate the impact of pre-treatment surgical staging, including removal of bulky lymph nodes, on disease-free survival in patients with locally advanced cervical cancer.MethodsUterus-11 was a prospective international multicenter study including patients with locally advanced cervical cancer who were randomized 1:1 to surgical staging (experimental arm) or clinical staging (control arm) followed by primary platinum-based chemoradiation. Patients with histologically proven squamous cell carcinoma, adenocarcinoma, or adenosquamous cancer International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIB–IVA underwent gynecologic examination and pre-treatment imaging including abdominal computed tomography (CT) and/or abdominal magnetic resonance imaging (MRI). Patients had chest imaging (any of the following: X-ray, CT, or PET-CT). The primary endpoint was disease-free survival and the secondary endpoint was overall survival. An ad hoc analysis was performed after trial completion for cancer-specific survival. Randomization was conducted from February 2009 to August 2013.ResultsA total of 255 patients (surgical arm, n=130; clinical arm, n=125) with locally advanced cervical cancer were randomized. Of these, 240 patients were eligible for analysis. The two groups were comparable with respect to patient characteristics. The surgical approach was transperitoneal laparoscopy in most patients (96.6%). Laparoscopic staging led to upstaging in 39 of 120 (33%) patients. After a median follow-up of 90 months (range 1–123) in both arms, there was no difference in disease-free survival between the groups (p=0.084). For patients with FIGO stage IIB, surgical staging is superior to clinical staging with respect to disease-free survival (HR 0.51, 95% CI 0.30 to 0.86, p=0.011). In the post-hoc analysis, surgical staging was associated with better cancer-specific survival (HR 0.61, 95% CI 0.40 to 0.93, p=0.020).ConclusionOur study did not show a difference in disease-free survival between surgical and clinical staging in patients with locally advanced cervical cancer. There was a significant benefit in disease-free survival for patients with FIGO stage IIB and, in a post-hoc analysis, a cancer-specific survival benefit in favor of laparoscopic staging. The high risk of distant metastases in both arms emphasizes the need for further evaluation.

Value of PET imaging for radiation therapy

“…Thus, laparoscopic staging is widely applied leading to upstaging in > 30% of locally advanced cervical cancer patients and allowing for treatment triage (radical hysterectomy versus definitive RCHT). Recently, the randomized trial Uterus-11 has shown that laparoscopic staging did not only avoid under-or overtreatment, but had an impact on disease-free survival and cancer-specific survival, respectively, without increased toxicity rates [137].…”

Laparoscopic Debulking of Enlarged Pelvic Nodes during Surgical Para-aortic Staging in Locally Advanced Cervical Cancer: A Retrospective Comparative Cohort Study

“…The recent results of the prospective trial Uterus-11 showed no differences in OS and PFS globally, although a significant benefit in DFS was found for patients with FIGO stage IIB and, in a post-hoc analysis, a cancer-specific survival benefit in favor of laparoscopic staging (27). However, in this study aortic lymphadenectomy was performed at the same time as pelvic lymphadenectomy, even in those cases that presented bulky pelvic nodes, and therefore the effects only at the pelvic level were not evaluated.…”

Value of PET imaging for radiation therapy

“…A prospective trial evaluated the use of laparoscopic staging after (false) negative FDG-PET/CT and showed significantly superior oncological outcomes for patients with lymph node metastases < 5 mm vs. > 5 mm after surgical staging and RCHT [141]. The shortcoming of the above mentioned Uterus-11 trial [137] is that FDG-PET/CT was not used in that study. The idea of combining the validation of FDG-PET/CT and laparoscopic staging has been discussed by the LilACS study group.…”

“…Thus, laparoscopic staging is widely applied leading to upstaging in > 30 % of locally advanced cervical cancer patients and allowing for treatment triage (radical hysterectomy versus definitive RCHT). Recently, the randomized trial Uterus-11 has shown that laparoscopic staging did not only avoid under-or overtreatment, but had an impact on disease-free survival and cancer-specific survival, respectively, without increased toxicity rates [137]. Laparoscopic staging therefore remains the gold standard for FIGO stage IIB and >IIB patients [137][138][139].…”

“…Recently, the randomized trial Uterus-11 has shown that laparoscopic staging did not only avoid under-or overtreatment, but had an impact on disease-free survival and cancer-specific survival, respectively, without increased toxicity rates [137]. Laparoscopic staging therefore remains the gold standard for FIGO stage IIB and >IIB patients [137][138][139].…”