ReviewCytoreductive surgery for recurrent ovarian cancer: A meta-analysis
Introduction
The American Cancer Society has estimated that 21,650 women in the United States will be diagnosed with ovarian cancer annually, and 15,520 women will die of this disease [1]. The concept of cytoreductive surgery for ovarian cancer has evolved since Meigs, in 1934, first proposed that as much tumor as possible should be removed to enhance the effects of post-operative irradiation [2]. Forty years after Meigs' initial proposition, Griffiths published the landmark study that first clearly delineated the inverse relationship between post-operative residual tumor size and patient survival [3]. More contemporary studies published by Hoskins et al., writing for the Gynecologic Oncology Group, demonstrated two important principles with respect to residual disease after primary surgery for advanced-stage ovarian cancer. First, there is a threshold effect, or a maximal diameter of residual disease above which even extensive efforts at cytoreduction will not impact survival [4]. Secondly, below this threshold there is also a continuum effect, such that the smaller the residuum, the better the survival outcome, with patients left with no gross residual disease having the most favorable prognosis [5].
Although the basic treatment paradigm of a maximum cytoreductive surgical effort prior to initiating platinum and taxane-based chemotherapy is well established, the majority of patients with advanced-stage epithelial ovarian cancer will ultimately experience tumor recurrence [6], [7]. For this reason, the therapeutic value of repeating the initial surgical treatment plan (cytoreduction) has been widely debated. Since the publication by Berek et al. in 1983, which first introduced the term “secondary cytoreduction”, the clinical scenarios, indications for, and anticipated outcomes of repeat tumor reductive operations for recurrent ovarian cancer have been more precisely defined [8], [9]. By most accounts, repeat or secondary cytoreductive surgery for recurrent ovarian cancer is defined as an operative procedure performed at some time remote (disease-free interval of more than 6 to 12 months) from the completion of primary therapy with the intended purpose of tumor reduction. Even within this narrowly defined clinical scenario, the potential utility of surgical cytoreduction remains controversial. Specifically, the survival impact of successful tumor reduction has been difficult to quantify in relation to other relevant clinical and biological prognostic characteristics. The objective of the current study was to aggregate the published literature on cytoreductive surgery for recurrent ovarian cancer to determine the relative effect of multiple prognostic variables on overall post-recurrence survival time among cohorts of surgical patients. The main research hypothesis concerning residual disease was that median overall post-recurrence survival time would be positively correlated with the proportion of patients in each cohort undergoing successful secondary cytoreductive surgery.
Section snippets
Study selection and data extraction
Using the headings and keywords “recurrent ovarian carcinoma,” “recurrent ovarian cancer,” “secondary cytoreductive surgery,” and “secondary surgical cytoreduction,” a MEDLINE search for English-language articles published between January 1, 1983 and July 31, 2007 was conducted. Research published only in abstract format was not included. Publications were selected for initial review if the study contained at least one cohort of patients with recurrent epithelial ovarian cancer undergoing
Study characteristics
The initial MEDLINE search yielded 876 articles. The full-length published reports of 101 of these studies were formally reviewed. Ultimately, 40 studies, encompassing 2019 patients, were identified as meeting the minimum study inclusion criteria (Table 1) [8], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50].
Discussion
For women with advanced-stage ovarian cancer, the treatment paradigm of maximal primary cytoreductive surgery followed by platinum and paclitaxel-based chemotherapy is well established, and a complete clinical response can be expected in over 50% of patients [51], [52]. For patients with progressive disease on front-line therapy or recurring shortly after completing initial chemotherapy, treatment options are limited and the prognosis is poor. On the other hand, ovarian cancer recurrence after
Conflict of interest statement
DSC has served on the Speakers' Bureau for Genzyme Inc. REB and IP have no conflicts of interest to declare.
Acknowledgments
This work supported by a grant from the Entertainment Industry Foundation and the Callaway Foundation Women's Cancer Initiative. The authors gratefully acknowledge the assistance of Dr. Bo Gronlund for providing additional unpublished data for inclusion in this study.
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