Elsevier

Gynecologic Oncology

Volume 108, Issue 2, February 2008, Pages 276-281
Gynecologic Oncology

The effect of maximal surgical cytoreduction on sensitivity to platinum-taxane chemotherapy and subsequent survival in patients with advanced ovarian cancer

https://doi.org/10.1016/j.ygyno.2007.10.022Get rights and content

Abstract

Objective. In advanced ovarian cancer, patients cytoreduced to no visible disease appear to have improved survival compared to patients with visible residual tumor ≤ 10 mm. It remains unresolved whether this is due to better chemotherapy response and/or simply “re-setting the clock,” such that patients with less residual disease take longer to recur and succumb to their disease.

Methods. We reviewed the records of all patients who had primary surgery for stage IIIC–IV ovarian cancer at our institution from 1998–2004, followed by intravenous platinum-taxane chemotherapy. Primary outcome measures were complete response (CR) to initial chemotherapy, platinum resistance at 6 months, progression-free (PFS), and overall survival (OS).

Results. A total of 296 patients met study criteria, of whom 64 (22%) had cytoreduction to no visible disease, 145 (49%) had 1–10 mm residual disease, and 87 (29%) had > 10 mm residual disease. After multivariate analyses, patients cytoreduced to no visible disease demonstrated significant improvements in rates of initial complete response and incidence of platinum resistance, as well as subsequent improvement in PFS and OS, compared to the other two groups. Similarly, patients with 1–10 mm residual disease had improved outcomes compared to patients with > 10 mm residual disease for each endpoint.

Conclusions. In ovarian cancer patients with < 10 mm residual disease who began platinum-taxane therapy, maximal cytoreduction to no visible residual disease was associated with improved initial chemotherapy response, less platinum resistance, and improved survival. Maximal cytoreduction may improve survival through increased sensitivity to initial chemotherapy and should be the goal of initial surgery in these patients.

Introduction

Of the 22,430 women estimated to be diagnosed with ovarian cancer in 2007, the majority will present at an advanced stage [1]. For these patients, standard initial therapy will entail primary cytoreductive surgery followed by combination platinum-taxane chemotherapy [2]. Of the many pretreatment prognostic factors associated with improved survival, few have had the durable effect of optimal primary cytoreduction [3].

The benefit of optimal primary cytoreduction is dependent on the availability of highly active chemotherapy, which should be more effective when tumor volume is reduced below a certain threshold. The Gynecologic Oncology Group (GOG) has used the threshold of ≤ 1 cm residual disease in greatest dimension to define “optimal” cytoreduction since 1986 [4]. Increasingly, reports have demonstrated that there may be an additional survival advantage associated with cytoreduction to no visible residual disease [5], [6], [7], [8], [9], [10]. It remains unresolved as to whether this improvement is due to increased chemotherapy sensitivity, more favorable “tumor biology,” and/or simply “re-setting the clock,” such that those with less residual disease take longer to recur and succumb to their disease.

The objective of this study was to explore the associations between residual disease categories after primary cytoreduction on initial chemotherapy response and resistance in patients with advanced ovarian cancer, and whether these associations had subsequent relevance to their time to recurrence and ultimate survival.

Section snippets

Methods

After obtaining Institutional Review Board approval, we identified all patients who underwent primary cytoreductive surgery at our institution between 1/98 and 12/04. The records of all patients with stage IIIC–IV epithelial ovarian cancer who subsequently received intravenous platinum-taxane chemotherapy were reviewed and compared as three groups based on residual disease at the completion of primary cytoreduction—no visible tumor, 1–10 mm residual, and > 10 mm residual disease. Exclusion

Results

During the study period, 296 patients met criteria for inclusion and were compared as three groups—no visible residual, 64 patients (22%); 1–10 mm residual, 145 patients (49%); and > 10 mm residual, 87 patients (29%). Patient characteristics, tumor features, and intraoperative findings between the three groups were compared (Table 1). The majority of patients in all three groups had stage IIIC disease, grade 3 tumors, and serous histology. Age at the time of surgery was equivalent, but patients

Discussion

Since the initial observations by Meigs, expanded more completely by Griffiths, a growing body of literature has supported the association between surgical cytoreduction and improved survival in advanced ovarian cancer [5], [6], [7], [8], [9], [10], [18], [19], [20], [21]. Two meta-analyses have summarized many of the reported studies thus far, and have demonstrated the longest survival in patients cytoreduced to no visible tumor [3], [22]. In their study, Bristow et al. evaluated 81 studies

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