The correlation between BRCA status and surgical cytoreduction in high-grade serous ovarian carcinoma

Abstract

<h3>Objectives:</h3> BRCA-associated ovarian cancers are biologically unique, as evident by differential molecular and clinical behaviour of these tumor as compared to sporadic ovarian cancers. It is unclear if these biological differences translate to favorable outcomes at the time of primary cytoreduction. The aim of this study is to compare the amount of residual disease after primary cytoreduction in <i>BRCA</i> mutated and wildtype populations, and to assess whether <i>BRCA</i> status is an independent predictor of optimal cytoreduction. <h3>Methods:</h3> We conducted a retrospective analysis of patients with high-grade serous (HGSC) ovarian cancers with known germline and somatic <i>BRCA</i> mutation status, treated with primary cytoreductive surgery from 2000 to 2017. Post-operative <i>BRCA</i> germline and somatic testing was conducted in all cases. We compared the complete, optimal and suboptimal cytoreduction rates between the <i>BRCA</i> positive and the <i>BRCA</i> negative cohorts and built a predictive model to assess whether the <i>BRCA</i> status was associated with the amount of residual disease after controlling for confounding variables. <h3>Results:</h3> Of 355 women with HGSC ovarian cancers treated with primary cytoreduction, 144 harbored germline or somatic <i>BRCA</i> mutations (41%) and 211 were <i>BRCA</i> wildtype (59%). <i>BRCA</i> positive women tended to be younger (54 vs 59; p<0.001), but there were no differences between the two groups in preoperative CA-125 levels, disease burden (measured by disease score), surgical complexity score, stage distributions, length of surgery, intraoperative or postoperative complications. Comparing residual disease burden at the end of primary cytoreduction, the <i>BRCA</i> positive group had a higher rate of complete cytoreduction to no residual disease (0mm) [75% vs 54%], and a lower rate of optimal cytoreduction (1-9mm) [16% vs 34%] or suboptimal cytoreduction (≥10mm) [9% vs. 12%] (p<0.001). In our predictive model, after accounting for length of surgery, CA-125 level, stage distributions, disease scores and surgical complexity scores, <i>BRCA</i> positive status was predictive of complete cytoreduction to 0mm residual disease with odds ratio (OR) of 4.78 (95% CI 2.32-9.85; p<0.001). Subgroup analysis restricted to patients with stage III/IV HGSC showed similar results, with <i>BRCA</i> positive status having OR of 5.2 (95% CI 2.44-11.09; p<0.001) for complete primary cytoreduction. <h3>Conclusions:</h3> <i>BRCA</i> status is predictive of complete and optimal cytoreduction at the time of primary surgical cytoreduction in patients presenting with newly diagnosed ovarian cancer. This positive correlation should be taken into consideration when deciding between primary cytoreductive surgery or neoadjuvant chemotherapy in women with this disease.