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Management of patients with early-stage ovarian clear cell carcinoma: risk stratification and fertility conservation
  1. Beryl Manning-Geist1,
  2. Sushmita Gordhandas1,
  3. Anjelica Hodgson2,
  4. Qin C Zhou3,
  5. Alexia Iasonos3,
  6. Dennis S Chi1,
  7. Lora Ellenson2,
  8. Carol A Aghajanian4,
  9. Nadeem R Abu-Rustum1,
  10. Mario Leitao1,
  11. Kara Long1,
  12. Maria M Rubinstein4,
  13. Yukio Sonoda1,
  14. Kaled Alektiar5,
  15. Britta Weigelt2,
  16. Oliver Zivanovic1 and
  17. Rachel N Grisham4
  1. 1Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
  2. 2Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
  3. 3Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
  4. 4Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
  5. 5Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
  1. Correspondence to Dr Rachel N Grisham, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; grishamr{at}mskcc.org

Abstract

Objective We sought to describe clinicopathologic and treatment factors associated with oncologic outcomes in patients with early-stage ovarian clear cell carcinoma undergoing complete staging and in a sub-set of these patients undergoing fertility-conserving surgery.

Methods We retrospectively identified patients with ovarian clear cell carcinoma initially treated at our institution from January 1, 1996 to March 31, 2020. Survival was estimated using Kaplan–Meier curves and compared by log-rank test. Survival-associated variables were identified by Cox proportional hazards regression.

Results Of 182 patients, mismatch repair and p53 protein expression were assessed by immunohistochemistry on 82 and 66 samples, respectively. There were no significant differences in progression-free survival or overall survival between mismatch repair-deficient (n=6, including 4 patients with Lynch syndrome; 7.3%) and mismatch repair-proficient patients, whereas aberrant p53 expression (n=3; 4.5%) was associated with worse progression-free (p<0.001) and overall survival (p=0.01). Patients with stage IA/IC1 disease had a 95% 5-year overall survival rate (95% CI 88% to 98%); patients with stage IC2/IC3 disease had a similar 5-year overall survival rate (76%; 95% CI 54% to 88%) to that of patients with stage IIA/IIB disease (82%; 95% CI 54% to 94%). There was no difference in 5-year overall survival in patients with stage IA/IC1 undergoing chemotherapy versus observation (94% vs 100%). Nine patients underwent fertility-sparing surgery and none experienced recurrence. Of five patients who pursued fertility, all had successful pregnancies.

Conclusions In patients with completely staged ovarian clear cell carcinoma, those with stage IA/IC1 disease have an excellent prognosis, regardless of chemotherapy. Aberrant p53 expression may portend worse outcomes. Additional investigation is warranted on the safety of fertility conservation in patients with stage IA/IC1 disease.

  • ovarian cancer

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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Footnotes

  • Twitter @leitaomd

  • BM-G and SG contributed equally.

  • Contributors Conceptualization: BM-G, SG, AH, DSC, BW, OZ, RG. Data curation: BM-G, SG, AH. Formal analysis: BM-G, SG, QCZ, AI. Methodology: QCZ, AI. Supervision: OZ, RG, BW, LE. RG is Guarantor.

  • Funding Research reported in this publication was supported in part by NCI Cancer Center Support Grant P30 CA008748 to the institution (supporting core resources). BW’s research is funded by NIH/NCI P50 CA247749, the Breast Cancer Research Foundation, and Cycle for Survival.

  • Competing interests AI has served as a consultant for Mylan. DSC has provided speaking services for AstraZeneca, served on advisory boards for Apyx Medical and Biom’Up, and holds or has held stock or stock options in Moderna, BioNTech, Doximity, and Apyx Medical. CAA has received research grants from Abbvie, Clovis, Genentech, and Astra Zeneca and served on advisory boards for Abbvie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, and Roche/Genentech. NRA-R has received research grants from GRAIL and Stryker/Novadaq. ML has received research grant(s) from KCI/Acelity, provided speaking services for Intuitive Surgical, and served on advisory boards for Johnson & Johnson/Ethicon and Takeda. MMR has received research grants from AstraZeneca, Merck, and Zentalis. BW has served on a scientific advisory board for Repare Therapeutics. RG has consulted for AstraZeneca, Corcept, GlaxoSmithKline, MJH Life Sciences, Natera, PER, and SpringWorks. All research grants were awarded to and administered by the institution.

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

  • 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.