Does neoadjuvant chemotherapy impair long-term survival for ovarian cancer patients? A nationwide Danish study
Introduction
Ovarian cancer is the leading cause of death among women with gynecological malignancies [1], [2], and a majority of patients are diagnosed at advanced stages of the disease, for which the prognosis is generally poor [1]. For decades, the traditional treatment has consisted of primary debulking surgery (PDS) and adjuvant chemotherapy, and there is a general consensus that the most important factor regarding survival is the presence of a residual tumor after surgery [3], [4]. Accordingly, extensive and aggressive surgery has been shown to be an effective method to achieve complete tumor resection and improve survival [5], [6]. However, this approach may not be beneficial for a subgroup of patients for whom surgery-related morbidity outweighs the benefit of a smaller residual tumor [7]. Recently, the use of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) has been suggested as an alternative first-line treatment. The potential benefit of NACT–IDS is that the debulking is more feasible and therefore better tolerated by patients than PDS, which may be important for patients in poor medical condition or advanced age or with extensive tumor load, as well as patients for whom preoperative diagnostics suggest an inadequate surgical outcome. Several studies have shown that IDS causes shorter hospital stay lengths [8], [9], [10], [11], [12], [13], [14], less intraoperative blood loss [8], [9], [10], [11], [13], [14], [15], [16], [17], less invasive surgery [9], [10], [12], [14], [18], [19], [20], fewer complications [12], [13], [18], [21], and better surgical outcomes with regard to residual tumor after surgery [9], [10], [11], [13], [16], [17], [18], [19], [20], [22], [23], [24], [25] compared with PDS.
Additionally, several studies have shown that NACT–IDS does not impair survival [9], [10], [11], [13], [14], [16], [17], [18], [19], [22], [23], [25], [26], in particular if the population is older or has stage IV disease [9], [10], [13], [18], [25], [26]. However, other studies have demonstrated that PDS is a superior treatment strategy compared with NACT–IDS [20], [27], [28], [29], and two meta-analyses have shown conflicting results [30], [31]. In 2010, Vergote et al. published data from the European Organisation for Research and Treatment of Cancer (EORCT) trial comparing survival for women with bulky stage IIIC or IV disease treated with PDS or NACT [32]. The study found no difference in survival between the two groups except for patients with tumor metastases < 5 cm, for whom overall survival was longer when treated with PDS. Also in 2010, Kumar et al. presented an abstract in which the survival of 147 women with stages IIIC and IV randomly assigned to PDS or NACT–IDS was found to be similar [33].
In Denmark, the use of NACT has increased in the previous decade for patients with advanced ovarian cancer [34]. Therefore, the aims of our study were to evaluate the treatment principles for advanced epithelial ovarian cancer in Denmark and to investigate the effect of the first-line treatments on overall survival and surgical outcomes.
Section snippets
Study population
Patients treated in the five Danish gynecological–oncological tertiary referral centers between January 1, 2005 and October 31, 2011 with primary epithelial stage IIIC or IV cancer in the ovaries, fallopian tubes, or peritoneum were included. In Denmark, treatment of ovarian cancer is centralized to the five tertiary referral centers, which treated 82% of patients from 2005 to 2011 and 94% of patients from 2009 to 2011 [1]. Patients were followed until February 14, 2013 or death, whichever came
Results
Of the 1677 women eligible for the study, 990 (59%) were treated with PDS (Group I), 515 (31%) were referred to NACT (Group II), and 172 (10%) were classified as having palliative treatment (Group III). Among the five centers, the use of PDS varied from 44% to 74% (p < 0.001). Of the 515 women referred to NACT, 335 (65%) underwent IDS (Group IIa) and 180 (35%) did not have IDS (Group IIb). A total of 352 women (21%) had no debulking surgery at any time during their treatment. Baseline
Discussion
This nationwide Danish retrospective cohort study aimed to evaluate whether treatment with NACT prior to debulking surgery affected overall survival and surgical outcomes. We found that NACT–IDS was associated with better surgical outcomes and with an increased risk of death after two years of follow-up. Patients without residual tumor after surgery had better survival when treated with PDS. For patients with stage IV disease and patients with residual tumor, no difference in survival between
Conflict of interests
All authors declare no conflict of interest.
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