Elsevier

Gynecologic Oncology

Volume 130, Issue 3, September 2013, Pages 493-498
Gynecologic Oncology

Survival impact of complete cytoreduction to no gross residual disease for advanced-stage ovarian cancer: A meta-analysis

https://doi.org/10.1016/j.ygyno.2013.05.040Get rights and content

Highlights

  • The proportion of patients left with no gross residual disease is independently predictive of survival.

  • The proportion of patients receiving intraperitoneal chemotherapy is a significant predictor of cohort survival time.

  • These data underscore the synergy between regional therapeutic efficacy and the completeness of surgical resection.

Abstract

Objective

To quantify the impact of complete cytoreduction to no gross residual disease on overall survival among patients with advanced-stage ovarian cancer treated during the platinum–taxane era.

Methods

PubMed and Cochrane Library databases were searched for all articles on primary cytoreductive surgery for advanced-stage ovarian cancer published from 1/1996 to 7/2011. A total of 18 relevant studies (13,257 patients) were identified for analysis. Simple and multiple linear regression analyses, with weighted correlation calculations, were used to assess the effect on median survival time of clinical and treatment-related factors.

Results

The mean weighted median overall survival time for all cohorts was 44.4 months (range, 27.6–66.9 months). Simple linear regression analysis revealed that residual disease, stage IV disease, and use of intraperitoneal chemotherapy were significantly associated with median survival time. After controlling for other factors on multiple linear regression analysis, each 10% increase in the proportion of patients undergoing complete cytoreduction to no gross residual disease was associated with a significant and independent 2.3-month increase (95%CI = 0.6–4.0, p = 0.011) in cohort median survival compared to a 1.8-month increase (95%CI = 0.6–3.0, p = 0.004) in cohort median survival for optimal cytoreduction (residual disease  1 cm). Each 10% increase in the proportion of patients receiving intraperitoneal chemotherapy was associated with a significant and independent 3.9-month increase (95%CI = 1.1–6.8, p = 0.008) in median cohort survival time.

Conclusions

For advanced-stage ovarian cancer treated during the platinum–taxane era, the proportions of patients left with no gross residual disease and receiving intraperitoneal chemotherapy are independently significant factors associated with the most favorable cohort survival time.

Introduction

Worldwide, approximately 225,000 women are diagnosed with ovarian cancer and 140,000 women die from this disease annually [1]. In the United States, ovarian cancer remains the leading cause of death from gynecological malignancy, with 21,990 new cases and 15,460 deaths in 2011 [1]. The majority of ovarian cancer patients are initially diagnosed with tumor metastases beyond the ovary, which results in diminished chances of long-term survival [2]. Surgical cytoreduction and adjuvant chemotherapy are the cornerstones of management for advanced ovarian cancer. Since the mid-1990s, primary cytoreductive surgery followed by platinum and taxane-based combination chemotherapy has been the standard treatment regimen for advanced-stage disease [3], [4], [5], [6].

Residual disease after cytoreductive surgery for advanced-stage ovarian cancer is estimated as the largest diameter of remaining tumor and is one of the most important prognostic factors [7], [8]. Paradoxically, universal consensus regarding the definition of “optimal” residual disease has been lacking. The Gynecologic Oncology Group (GOG) has defined optimal residual disease as residual tumor  1 cm in the largest diameter [9], [10]. However, optimal residual disease has been variously defined as ranging from no gross residual disease to remaining tumor nodules measuring  2 cm [11], [12], [13], [14]. More contemporary data suggest that the most favorable survival outcomes are associated with complete cytoreduction to no gross residual disease [15], [16], [17], [18], [19], [20], [21], [22]. Despite this observation the relative impact of complete cytoreduction, as opposed to “optimal but visible residual disease”, within the context of contemporary platinum–taxane-based adjuvant therapy has been difficult to determine. Therefore, the objective of the current study was to quantify the impact of complete cytoreduction to no gross residual disease on overall survival among patients with advanced-stage ovarian cancer treated during the platinum–taxane era using the technique of meta-analysis.

Section snippets

Study selection and data extraction

Potential articles for analysis were identified from a literature search of the National Library of Medicine (PubMed) and the Cochrane Library for all English-language publications between January 1, 1996 and July 31, 2011. The keywords used were “ovarian neoplasm,” “ovarian carcinoma,” “ovarian cancer,” and “surgery.” Two authors (S.J.C. and R.E.B.) independently reviewed the titles and abstracts of publications searched, and excluded the unrelated articles. A full-text audit of identified

Study characteristics

The initial electronic search yielded 1203 articles. The full-length published reports of 104 studies were formally reviewed, and 15 studies were identified as containing the minimum study inclusion criteria [5], [15], [16], [17], [18], [19], [20], [21], [23], [24], [25], [26], [27], [28], [29]. Of these 15 studies, 4 studies [18], [19], [20], [21] were ancillary data studies which retrospectively reanalyzed the data collected for 9 previous randomized prospective trials [5], [6], [23], [30],

Discussion

Meigs first described cytoreductive surgery for advanced ovarian cancer in 1934 [36]. Forty years later, Griffiths published a landmark study that conclusively demonstrated an inverse relationship between residual tumor diameter and patient survival [37]. Nearly every retrospective study and prospective study since then has demonstrated that the extent of residual disease and the use of platinum-based chemotherapy are key factors impacting survival in women with advanced staged ovarian cancer.

Conflict of interest statement

The authors do not have any potential conflicts of interest.

Acknowledgment

Dr. Robert E. Bristow was supported by the Queen of Hearts Foundation.

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