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Primary cytoreductive surgery compared with neoadjuvant chemotherapy in patients with BRCA mutated advanced high grade serous ovarian cancer: 10 year survival analysis
  1. Soyoun Rachel Kim1,
  2. Ashna Parbhakar2,
  3. Xuan Li3,
  4. Marcus Q Bernardini4,
  5. Liat Hogen5 and
  6. Taymaa May6,7
    1. 1Division of Gynaecologic Oncology, Princess Margaret Cancer Centre/University Health Network/Sinai Health Systems, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
    2. 2University of Toronto, Toronto, Ontario, Canada
    3. 3Department of Biostatistics, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
    4. 4Princess Margaret Cancer Centre/University Health Network/Sinai Health Systems, Princess Margaret Hospital, Toronto, Ontario, Canada
    5. 5Gynaecologic Oncology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
    6. 6Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
    7. 7Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada
    1. Correspondence to Dr Taymaa May, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2MP, Canada; taymaamay{at}gmail.com

    Abstract

    Objectives Given the high response to platinum based chemotherapy in BRCA 1/2 mutated high grade serous ovarian cancers, there is uncertainty about the relative benefits of primary cytoreductive surgery versus neoadjuvant chemotherapy in this population. We aimed to compare the survival outcomes for women with BRCA 1/2 mutated high grade serous ovarian cancers undergoing either primary cytoreductive surgery or neoadjuvant chemotherapy.

    Methods We conducted a retrospective cohort study of all stage III/IV BRCA mutated high grade serous ovarian cancers treated with primary cytoreductive surgery or neoadjuvant chemotherapy at a single tertiary cancer center between 1991 and 2020. Baseline demographics, initial disease burden, surgical complexity, and survival outcomes were examined.

    Results Of 314 women with germline or somatic BRCA mutations, 194 (62%) underwent primary cytoreductive surgery and 120 (38%) underwent neoadjuvant chemotherapy followed by interval cytoreductive surgery. Those undergoing primary cytoreductive surgery were younger (median age 53 years (range 47–59) vs 59 years (50–65), p<0.001), but there were no differences in functional status or underlying comorbidities. The initial disease burden was lower (disease score high (40% vs 44%; p<0.001) but surgical complexity was higher (surgical complexity score high (18% vs 3%; p<0.001) in the primary cytoreductive surgery cohort. The rate of optimal or complete cytoreduction was similar in both groups (89% vs 90%; p=0.23) as well as the rate of poly (ADP-ribose) polymerase inhibitor use (62% vs 68%; p=0.3). The 10 year overall survival and recurrence free survival were superior in the primary cytoreductive surgery cohort (overall survival 49% vs 25%, p<0.001 and progression free survival 25% vs 10%, p<0.001). After controlling for confounders, primary cytoreductive surgery remained a significant predictor of improved overall survival (hazard ratio (HR) 0.45; 95% confidence interval (CI) 0.27 to 0.74; p=0.002) and recurrence free survival (HR 0.55; 95% CI 0.37 to 0.80; p=0.002).

    Conclusions Primary cytoreductive surgery was associated with improved survival in women with stage III/IV BRCA mutated high grade serous ovarian cancers compared with neoadjuvant chemotherapy.

    • Ovarian Cancer
    • BRCA1 Protein
    • BRCA2 Protein
    • Cystadenocarcinoma, Serous
    • Cytoreduction surgical procedures

    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • Contributors SRK: data curation, formal analysis, project administration, visualization, writing—original draft, and writing—review and editing. AP: data curation, writing—original draft, and writing—review and editing. XL: formal analysis, writing—original draft, and writing—review and editing. MQB: data curation and writing—review and editing. LH: data curation and writing—review and editing. TM: conceptualization, data curation, formal analysis, funding acquisition, project administration, investigation, methodology, supervision, writing—review and editing and guarantor.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

    • Competing interests None declared.

    • 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.