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 Cancer Group

Int J Radiat Oncol Biol Phys. 2016 Feb 1;94(2):243-53. doi: 10.1016/j.ijrobp.2015.10.027. Epub 2015 Oct 20.

Abstract

Purpose: 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.

Methods and materials: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Brachytherapy / adverse effects
  • Carboplatin / therapeutic use
  • Carcinoma, Adenosquamous / mortality
  • Carcinoma, Adenosquamous / psychology
  • Carcinoma, Adenosquamous / therapy
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Chemoradiotherapy / adverse effects*
  • Cisplatin / therapeutic use
  • Disease-Free Survival
  • Female
  • Germany
  • Gynecology
  • Humans
  • Lymph Node Excision / methods
  • Middle Aged
  • Neoplasm Staging / methods*
  • Prospective Studies
  • Radiation Oncology
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / therapy*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Carboplatin
  • Cisplatin