The optimal time for surgery in women with serous ovarian cancer.

Epithelial ovarian cancer is the most common cause of death from gynecologic malignancy.1 High-grade serous ovarian cancer (HGSC) is the most common type of epithelial ovarian cancer, representing 70% of all diagnosed tumours.2 Most ovarian cancers (70%) are diagnosed at an advanced stage of disease (Stage III/IV), and 80%–90% of these advanced-stage tumours are HGSC.3 As such, the 5-year overall survival rate for women with HGSC is approximately 44%. The standard of care treatment for HGSC has essentially remained the same for the past 2 decades and includes a combination of surgical cytoreduction and platinum-/taxane-based adjuvant chemotherapy.4,5 However, despite aggressive surgery and chemotherapy, cure is rare for the majority of women with HGSC. Survival in these patients largely depends on the tumour sensitivity to platinum-based chemotherapy6,7 and the degree of surgical cytoreduction.8,9 Even extensive surgeries leaving more than 1 cm of residual tumour have limited impact on survival.10–12 Since the original publication by Griffiths,9 which suggested an association between the amount of residual disease and survival, the definition of “optimal” cytoreduction has been shifting from an initial definition of no single residual lesion measuring less than 2 cm in diameter to a definition of less than 1 cm and, most recently, to a definition of no macroscopic disease.13–15 As optimal surgical cytoreduction is one of the strongest predictors of outcome for patients with HGSC, many studies have investigated the use of neoadjuvant chemotherapy as an alternative treatment strategy to reduce tumour burden before surgery.16 There are several putative advantages of the neoadjuvant treatment strategy, including less extensive surgery, reduced morbidity and increased optimal cytoreduction. Furthermore, it currently provides the only means to identify patients with platinum-resistant disease at presentation.17 Many studies suggest equivalent survival in patients receiving adjuvant versus neoadjuvant chemotherapy.18–28 Notably, Vergote and colleagues20 reported the only phase III randomized controlled trial in which patients with advanced-stage HGSC were treated with either primary surgery and adjuvant platinum-based chemotherapy (PCS group) or neoadjuvant platinum-based chemotherapy followed by interval cytoreductive surgery and additional adjuvant chemotherapy (NAC group). Although patients in the NAC group had higher rates of optimal cytoreduction and fewer perioperative complications, this did not translate into improved survival. This trial was criticized by many for poor progression-free and overall survival rates in both study arms.29–31 Importantly, several studies addressing the use of primary surgery versus neoadjuvant chemotherapy indicated that patients in the NAC group have inferior overall survival than patients in the PCS group.32–34 Bristow and Chi16 conducted a meta-analysis that suggested the number of neoadjuvant chemotherapy cycles before surgery was inversely proportional to the median overall survival. In addition, these authors demonstrated that although the difference in survival between the NAC and PCS groups did not reach statistical significance in previous studies, survival was often reduced by up to half in the NAC group.19 Hence, controversy remains about the use of neoadjuvant chemotherapy as a first-line treatment in patients with HGSC. Surveys of members of the Society of Gynecolologic Oncology35 and the European Society of Gynecologic Oncology36 suggest that 18% and 70% of gynecologic oncologists, respectively, routinely recommend neoadjuvant chemotherapy to their patients. Furthermore, the appropriate number of neoadjuvant chemotherapy cycles that should be administered before interval cytoreductive surgery is subject to debate. Hence, a deeper understanding of the effect of the treatment strategy, post-treatment tumour biology and survival outcomes are required. In this study, we examine the progression-free and overall survival of patients in the NAC group as compared with patients in the PCS group. The objective of this work was to study surgical factors, including the timing of surgery, in relation to the number of preoperative neoadjuvant chemotherapy cycles and the rate of optimal cytoreduction in the NAC and PCS groups. We aimed to analyze the impact of these factors on survival in women with HGSC.