Elsevier

Gynecologic Oncology

Volume 131, Issue 1, October 2013, Pages 15-20
Gynecologic Oncology

The time interval from surgery to start of chemotherapy significantly impacts prognosis in patients with advanced serous ovarian carcinoma — Analysis of patient data in the prospective OVCAD study

https://doi.org/10.1016/j.ygyno.2013.07.086Get rights and content

Highlights

  • Performance status, extent of surgery and complications correlated with timing of chemotherapy.

  • Delayed start of chemotherapy was associated with impaired prognosis.

Abstract

Objective

Cytoreductive surgery and platinum-based systemic therapy constitute the standard treatment of patients with advanced ovarian cancer. The aim of the present study was to evaluate whether the time interval from surgery to start of chemotherapy has an impact on clinical outcome.

Methods

Data of 191 patients with advanced serous (FIGO III–IV) ovarian cancer from the prospective multicenter study OVCAD (OVarian CAncer Diagnosis) were analyzed. All patients underwent primary surgery followed by platinum-based chemotherapy.

Results

The 25%, 50%, and 75% quartiles of intervals from surgery to start of chemotherapy were 22, 28, and 38 days, respectively (range, 4–158 days). Preoperative performance status (P < 0.001), extent of surgery (P < 0.001), and perioperative complications (P < 0.001) correlated with intervals from surgery to initiation of chemotherapy. Timing of cytotoxic treatment [≤ 28 days versus > 28 days; hazard ratio (HR) 1.73 (95% confidence interval 1.08–2.78), P = 0.022], residual disease [HR 2.95 (95% confidence interval 1.87–4.67), P < 0.001], and FIGO stage [HR 2.26 (95% confidence interval 1.41–3.64), P = 0.001] were significant prognostic factors for overall survival in multivariate analysis. While the interval from surgery to start of chemotherapy did not possess prognostic significance in patients without postoperative residual disease (n = 121), it significantly correlated with overall survival in patients with postoperative residual disease [n = 70, HR 2.24 (95% confidence interval 1.08–4.66), P = 0.031].

Conclusion

Our findings suggest that delayed initiation of chemotherapy might compromise overall survival in patients with advanced serous ovarian cancer, especially when suboptimally debulked.

Introduction

Due to the lack of an effective screening method and unspecific symptoms, 75% of patients with ovarian cancer are diagnosed in advanced stages of the disease [1]. Current standard treatment consists of surgery aimed at maximal cytoreduction and platinum-based chemotherapy. Studies on which this practice is based did not define the optimal timing of chemotherapy after surgery [2]. It is unclear whether delayed commencement of cytotoxic treatment adversely affects prognosis of patients with ovarian cancer. Patient factors such as postoperative complications or health-system logistic factors such as delays in referral or wait time may cause delays in time to chemotherapy. Most clinicians, however, assume that adjuvant chemotherapy should commence as soon as possible. This hypothesis is supported by studies in animal models that show that the time interval from surgery to chemotherapy influences growth of metastases [3]. Also, clinical studies in patients with breast and colon cancer demonstrate an increased mortality among patients with delayed initiation of cytotoxic treatment [4], [5].

To date, few studies have evaluated the prognostic importance of the interval from surgery to chemotherapy in patients with ovarian cancer. Initial reports did not observe an association between the timing of cytotoxic treatment after surgery and survival [6], [7], [8], [9], [10], [11]. Recently, two studies reported an impaired prognosis in patients with a delayed start of postoperative chemotherapy in elderly women and in patients without residual tumor after primary surgery [12], [13], [14]. These results must be interpreted with caution, as most studies included heterogeneous patient cohorts comprising various histological subtypes and different chemotherapeutic regimens.

The aim of the present study was to analyze the prognostic relevance of the time interval from surgery to platinum-based chemotherapy in a homogeneous group of patients with advanced serous ovarian cancer enrolled in the prospective multicenter OVCAD (OVarian CAncer Diagnosis) study.

Section snippets

Patients

Between August 2005 and December 2008, 275 consecutive patients diagnosed with primary advanced ovarian carcinoma at the Departments of Gynecology and Obstetrics in Berlin (n = 98), Leuven (n = 79), Hamburg (n = 46), Vienna (n = 42), and Innsbruck (n = 11) were enrolled in the OVCAD (Ovarian Cancer Diagnosis of a Silent Killer) project. This project aimed to investigate new predictors for early detection of minimal residual disease in epithelial ovarian cancer. Five European gynecologic cancer centers

Results

Clinicopathological parameters of the 191 patients with primary advanced ovarian cancer are provided in Table 1. The median follow-up was 42 months (range, 4–69 months).

The median time interval from primary surgery to the start of platinum-based chemotherapy was 28 days (range, 4–158 days). The 25th and 75th percentiles are 22 and 38 days, respectively.

Preoperative ECOG performance status (P < 0.001), extent of primary surgery (P < 0.001), and perioperative complications (P < 0.001) correlated with timing

Discussion

The present study demonstrates impaired overall survival in patients with advanced serous ovarian cancer and prolonged interval from surgery to platinum-based chemotherapy.

A previous study similarly reported an impact of interval between surgery and chemotherapy on prognosis. However, in contrast to the present study, the authors found that only patients without residual disease are affected by the timing of chemotherapy initiation [14]. This discrepancy may reflect key differences in the study

Conflict of interest statement

The authors do not have any conflicts of interest to disclose.

Acknowledgments

The OVCAD project was a Sixth Framework Program Project of the European Union (www.ovcad.eu).

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