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External beam radiotherapy versus vaginal brachytherapy in patients with stage II endometrial cancer: a systematic review and meta-analysis
  1. Deepa Maheswari Narasimhulu1,
  2. Adela Cope1,
  3. Irbaz Bin Riaz2,
  4. Ivy Petersen3,
  5. William Cilby1,
  6. Carrie Langstraat1,
  7. Gretchen Glaser1,
  8. Amanika Kumar1,
  9. Serena Cappuccio1,4,
  10. Mohammad Hassan Murad5,
  11. Colin West6,7 and
  12. Andrea Mariani1
  1. 1 Gynecologic Surgery, Mayo Clinic, Rochester, New York, USA
  2. 2 Hematology and Oncology, Mayo Clinic Rochester, Rochester, Minnesota, USA
  3. 3 Radiation Oncology, Mayo Clinic Rochester, Rochester, Minnesota, USA
  4. 4 Fondazione Policlinico Universitario A. Gemelli irccs, Roma, Italy
  5. 5 Center for Science of Health Care Delivery, Mayo Clinic Rochester, Rochester, Minnesota, USA
  6. 6 Internal Medicine, Mayo Clinic Rochester, Rochester, Minnesota, USA
  7. 7 Biomedical Statistics and Informatics, Mayo Clinic Rochester, Rochester, Minnesota, USA
  1. Correspondence to Dr Andrea Mariani, Gynecologic Surgery, Mayo Clinic, Rochester, MN 55905, USA; mariani.andrea{at}mayo.edu

Abstract

Objective The choice of adjuvant treatment for women with stage II endometrial cancer is challenging, given the known increase in morbidity with external beam radiation compared with vaginal brachytherapy, and the lack of consensus on its benefits. We summarized the evidence on survival and recurrence for stage II endometrial cancer, defined as cervical stromal invasion, after adjuvant postoperative external beam radiotherapy and vaginal brachytherapy.

Methods We searched the MEDLINE, EMBASE, CENTRAL, and Scopus databases from inception to January 2019 to identify studies that compared adjuvant postoperative external beam radiotherapy with or without vaginal brachytherapy and vaginal brachytherapy alone in stage II endometrial cancer. Our primary outcome was the locoregional recurrence rate, defined as recurrence in the pelvis or vagina. Secondary outcomes included the rate of recurrence at any site, distant recurrence rate, vaginal recurrence rate, pelvic recurrence rate, and 5 year overall survival. Study selection, assessment, and data abstraction were performed by an independent set of reviewers. Random effects models were used to synthesize quantitative data.

Results We included 15 cohort studies reporting data on 1070 women. Most women with stage II endometrial cancer (848/1070, 79.3%) were treated with external beam radiotherapy with or without vaginal brachytherapy. Subgroup analysis was stratified by whether >90% of the women included underwent pelvic lymph node assessment (sampling or full dissection). Locoregional recurrence (pelvic and vaginal recurrence) was significantly reduced with external beam radiotherapy with or without vaginal brachytherapy compared with vaginal brachytherapy alone (14 studies (n=1057); odds ratio (OR) 0.33 (95% confidence interval (CI) 0.16 to 0.68); I2=5%) regardless of pelvic lymph node assessment. Most women (81.8%) who recurred locoregionally had a least one uterine risk factor (grade 3 tumor, myometrial invasion >50%, or lymphovascular invasion). There was no difference in overall survival with external beam radiotherapy with or without vaginal brachytherapy compared with vaginal brachytherapy alone (five studies (n=463); OR 0.78 (95% CI 0.34 to 1.80); I2=48%).

Conclusions External beam radiotherapy with or without vaginal brachytherapy decreased the locoregional recurrence threefold for stage II endometrial cancer, regardless of pelvic lymph node assessment. Most women who suffered recurrence locoregionally had a least one high risk factor. Vaginal brachytherapy alone may be sufficient therapy for node negative stage II endometrial cancer without uterine risk factors, while those with uterine risk factors should be considered for external beam radiotherapy with or without vaginal brachytherapy to improve locoregional control.

  • endometrial neoplasms
  • radiation
  • brachytherapy
  • neoplasm recurrence, local
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Footnotes

  • Contributors Study conception and design: DMN, AC, AM, IP, HM, and CW. Acquisition of the data: DMN and AC. Analysis and interpretation of the data: DMN. Drafting of the manuscript: DMN. Critical revision: AM, AC, IBR, IP, WC, CL, GG, AK, SC, HM, and CW. DMN is responsible for the statistical analyses.

  • Funding This publication was supported by CTSA grant No UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH. NIH had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data sharing not applicable as no datasets generated and/or analyzed for this study. Not applicable for meta-analysis.

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