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Adjuvant chemotherapy in early-stage endometrioid endometrial cancer with >50% myometrial invasion and negative lymph nodes
  1. Francesco Multinu1,2,
  2. Simone Garzon1,3,
  3. Amy L Weaver4,
  4. Michaela E. McGree4,
  5. Enrico Sartori5,
  6. Fabio Landoni6,
  7. Paolo Zola7,
  8. Giorgia Dinoi1,8,
  9. Giovanni Aletti2,9,
  10. Matthew S Block10,
  11. Angiolo Gadducci11 and
  12. Andrea Mariani1
  1. 1Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA
  2. 2Division of Gynecologic Oncology, IEO, European Institute of Oncology IRCCS, Milan, Lombardia, Italy
  3. 3Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, Varese, Lombardia, Italy
  4. 4Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
  5. 5Department of Obstetrics and Gynecology, University of Brescia, Brescia, Lombardia, Italy
  6. 6Department of Medicine and Surgery, Clinic of Obstetrics and Gynecology, San Gerardo Hospital, University of Milan-Bicocca, Monza, Lombardia, Italy
  7. 7Department of Surgical Sciences, University of Turin, Torino, Piemonte, Italy
  8. 8Division of Gynecologic Oncology, Department of Women and Child Health, Catholic University of the Sacred Heart, Roma, Lazio, Italy
  9. 9Department of Hematology and Hemato-Oncology, European Institute of Oncology, Milano, Lombardia, Italy
  10. 10Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA
  11. 11Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Toscana, Italy
  1. Correspondence to Dr Andrea Mariani, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN 55905, USA; mariani.andrea{at}


Objective The role of adjuvant chemotherapy as an addition or alternative to radiotherapy for early-stage high-risk endometrioid endometrial cancer is controversial. This study aimed to investigate the role of adjuvant chemotherapy in early-stage high-risk endometrioid endometrial cancer.

Methods We identified patients with stage I or II endometrioid grade 2 or 3 endometrial cancer with myometrial invasion >50% and negative lymph nodes after pelvic with or without para-aortic lymphadenectomy at four institutions (USA and Italy). Associations between chemotherapy and cause-specific and recurrence-free survival were assessed with Cox proportional hazards models. Hematogenous, peritoneal, and lymphatic recurrences were defined as 'non-vaginal'.

Results We identified 329 patients of mean (SD) age 66.4 (9.8) years. The median follow-up among those alive was 84 (IQR 44–133) months. The 5-year cause-specific survival was 86.1% (95% CI 82.0% to 90.4%) and the 5-year recurrence-free survival was 82.2% (95% CI 77.9% to 86.8%). Stage II (vs stage IB) was associated with poorer cause-specific and recurrence-free survival. A total of 58 (90.6%) of 64 patients who had chemotherapy had 4–6 cycles of platinum-based regimen. In adjusted analysis, we did not observe a statistically significant improvement in cause-specific survival (HR 0.34; 95% CI 0.11 to 1.03; p=0.06) or non-vaginal recurrence-free survival (HR 0.36; 95% CI 0.12 to 1.08; p=0.07) with adjuvant chemotherapy. Sixteen of 18 lymphatic recurrences (88.9%; 3/5 pelvic, all 13 para-aortic) were observed in the 265 patients who did not receive adjuvant chemotherapy. Among stage II patients, no deaths (100% 5-year recurrence-free survival) were observed in the eight patients who received adjuvant chemotherapy compared with 66% 5-year recurrence-free survival in the 34 patients who did not.

Conclusion Although we observed that adjuvant chemotherapy was associated with improved oncologic outcomes in early-stage high-risk endometrioid endometrial cancer, the associations did not meet conventional levels of statistical significance. Further research is warranted in this relatively uncommon subgroup of patients.

  • endometrial neoplasms

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  • FM and SG are joint first authors.

  • AG and AM are joint senior authors.

  • Twitter @Fmultinu

  • FM and SG contributed equally.

  • Contributors Conception and design of the study: FM, AM, AG, and SG. Data collection, analysis, and interpretation: ALW, MM, SG, FM, AM, AG, ES, FL, and PZ. Writing, review, and editing the manuscript: all authors.

  • Funding This publication was made possible by the Clinical and Translational Science Awards (CTSA) Program through grant number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). This work was partially supported by the Italian Ministry of Health with Ricerca Corrente and 5×1000 funds.

  • Disclaimer The funders had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

  • Competing interests MSB received institutional (not personal) research support from Bristol-Myers Squibb Co, Merck & Co, Genentech, Pharmacyclics, Transgene, Immune Design, and Marker Therapeutics outside the present work.

  • Patient consent for publication Not required.

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

  • Data availability statement Data are available upon reasonable request. In accordance with the journal’s guidelines, we will provide our data for the reproducibility of this study in other centers if such is requested.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.