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.

Revised 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. Uterus-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. A 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). Our 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.

Marnitz S ，Tsunoda AT ，Martus P ，Vieira M ，Affonso Junior RJ ，Nunes J ，Budach V ，Hertel H ，Mustea A ，Sehouli J ，Scharf JP ，Ulrich U ，Ebert A ，Piwonski I ，Kohler C ... -  《-》

Perioperative morbidity and rate of upstaging after laparoscopic staging for patients with locally advanced cervical cancer: results of a prospective randomized trial.

The International Federation of Gynecology and Obstetrics (FIGO) staging for cervical cancer is based on clinical examination. Previous studies have demonstrated significant upstaging with surgical staging. However, no randomized trial has ever shown a survival benefit when radiation combined with chemoradiation (RCTX) is modified according to surgical staging. The objective of the study was to evaluate the feasibility and outcomes of surgical staging prior to radical RCTX treatment among patients with locally advanced cervical cancer in the setting of a larger, prospective, randomized study (the Uterus-11 study of the German Gynecologic Oncology Group). Between 2009 and 2013, 255 patients with advanced cervical cancer (FIGO IIB-IVA) were randomized to surgical staging and RCTX (arm A) or RCTX (arm B). RCTX in both arms included pelvic external beam radiotherapy with weekly cisplatin at 40 mg/m(2) and brachytherapy. Extended-field radiation was performed in cases of confirmed paraaortic metastases. One hundred thirty patients were randomized to surgical staging; 121 were eligible for this analysis. The mean patient age was 47.2 years, and the mean body mass index was 26.2 kg/m(2); the FIGO stages were IIB, IIIA, IIIB, and IVA in 85 (70.2%), 4 (3.3%), 29 (24%), and 3 (2.5%) patients, respectively. Arm A and arm B were similar with respect to Karnofsky performance status, histology, comorbidities, and lymphovascular space involvement. The surgical approach was transperitoneal laparoscopy in nearly all patients (93.4%), with no operative mortality. One patient (0.8%) had a conversion to laparotomy; 2 patients had more than 500 mL blood loss; the early postoperative complication rate was 7.3%. A mean of 19 pelvic and 17 paraaortic nodes were removed, with means of 2.4 and 1.3 positive nodes, respectively. RCTX began between 7 and 21 days after surgery. Operative staging led to upstaging in 40 of 121 (33%). Surgical staging in patients with locally advanced cervical cancer is safe and does not delay primary RCTX in a randomized study.

Köhler C ，Mustea A ，Marnitz S ，Schneider A ，Chiantera V ，Ulrich U ，Scharf JP ，Martus P ，Vieira MA ，Tsunoda A ... -  《-》

Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients-Acute Toxicity and Treatment Quality of the Uterus-11 Multicenter Phase III Intergroup Trial of the German Radiation Oncology Group and the Gynecologic C

The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique. A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratified by treatment arm and radiation technique. A total of 240 patients were eligible (n=121 in arm A; n=119 in arm B). Of the 240 patients, 236 (98.3%) underwent external beam RT with a median total dose of 50.4 Gy. The mean treatment duration was 53 days. Of the patients, 60% underwent intensity modulated RT (IMRT). A total of 234 patients (97.5%) underwent chemotherapy, and 231 (96.3%) underwent brachytherapy, with a median single dose of 6 Gy covering the tumor to a median nominal total dose of 28 Gy. Treatment was well tolerated, with 0% grade ≥3 genitourinary and gastrointestinal toxicity, 6% grade 3 nausea, 3% grade 3 vomiting, and <2% grade 3 diarrhea. More patients after surgical staging experienced grade 2 anemia (54.3% in arm A vs 45.3% in arm B; P=.074) and grade 2 leukocytopenia (41.4% vs 31.6%; P=.56). Of the patients who received IMRT versus a 3-dimensional technique, 65.3% versus 33.7% presented with grade 2 anemia. Grade 3 gastrointestinal and grade 2 bladder toxicity were significantly reduced with the use of IMRT. The incidence and severity of acute therapy-related toxicity compared favorably with those from other randomized trials. Excellent adherence to treatment and treatment quality was achieved compared with patterns of care analyses. Surgical staging led to a doubled number of patients treated with extended field RT. The question of whether surgical staging is beneficial in the context of primary CRT requires further study.

Marnitz S ，Martus P ，Köhler C ，Stromberger C ，Asse E ，Mallmann P ，Schmidberger H ，Affonso Júnior RJ ，Nunes JS ，Sehouli J ，Budach V ... -  《-》

Is there a benefit of pretreatment laparoscopic transperitoneal surgical staging in patients with advanced cervical cancer?

Marnitz S ，Köhler C ，Roth C ，Füller J ，Hinkelbein W ，Schneider A ... -  《GYNECOLOGIC ONCOLOGY》

Pre-treatment surgical para-aortic lymph node assessment in locally advanced cervical cancer.

Brockbank E ，Kokka F ，Bryant A ，Pomel C ，Reynolds K ... -  《Cochrane Database of Systematic Reviews》