Does neoadjuvant chemotherapy impair long-term survival for ovarian cancer patients? A nationwide Danish study

Highlights

• Treatment with neoadjuvant chemotherapy may impair long-term survival.

• For patients without residual tumor, primary surgery was associated with better survival.

• Interval debulking surgery was associated with peri-operative benefits.

Abstract

Objective

In Denmark, the proportion of women with ovarian cancer treated with neoadjuvant chemotherapy (NACT) has increased, and the use of NACT varies among center hospitals. We aimed to evaluate the impact of first-line treatment on surgical outcome and median overall survival (MOS).

Methods

All patients treated in Danish referral centers with stage IIIC or IV epithelial ovarian cancer from January 2005 to October 2011 were included. Data were obtained from the Danish Gynecological Cancer Database, the Danish National Patient Register and medical records.

Results

Of the 1677 eligible patients, 990 (59%) were treated with primary debulking surgery (PDS), 515 (31%) with NACT, and 172 (10%) received palliative treatment. Of the patients referred to NACT, 335 (65%) received interval debulking surgery (IDS). Patients treated with NACT–IDS had shorter operation times, less blood loss, less extensive surgery, fewer intraoperative complications and a lower frequency of residual tumor (p < 0.05 for all). No difference in MOS was found between patients treated with PDS (31.9 months) and patients treated with NACT–IDS (29.4 months), p = 0.099. Patients without residual tumor after surgery had better MOS when treated with PDS compared with NACT–IDS (55.5 and 36.7 months, respectively, p = 0.002). In a multivariate analysis, NACT–IDS was associated with increased risk of death after two years of follow-up (HR: 1.81; CI: 1.39–2.35).

Conclusions

No difference in MOS was observed between PDS and NACT–IDS. However, patients without residual tumor had superior MOS when treated with PDS, and NACT–IDS could be associated with increased risk of death after two years of follow-up.

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.