Elsevier

Gynecologic Oncology

Volume 112, Issue 1, January 2009, Pages 265-274
Gynecologic Oncology

Review
Cytoreductive surgery for recurrent ovarian cancer: A meta-analysis

https://doi.org/10.1016/j.ygyno.2008.08.033Get rights and content

Abstract

Objective

To determine the relative effect of multiple prognostic variables on overall post-recurrence survival time among cohorts of patients with recurrent ovarian cancer undergoing cytoreductive surgery.

Methods

Forty cohorts of patients with recurrent ovarian cancer (2019 patients) meeting study inclusion criteria were identified from the MEDLINE database (1983–2007). Simple and multiple linear regression analyses, with weighted correlation calculations, were used to assess the effect on median post-recurrence survival time of the following variables: year of publication, age, disease-free interval, localized disease, tumor grade and histology, the proportion of patients undergoing complete cytoreductive surgery, requirement for bowel resection, and the sequence of cytoreductive surgery and salvage chemotherapy.

Results

The mean weighted median disease-free interval prior to cytoreductive surgery was 20.2 months, and the mean weighted median overall post-recurrence survival time was 30.3 months. The weighted mean proportion of patients in each cohort undergoing complete cytoreductive surgery was 52.2%. Median survival improved with increasing year of publication (p = 0.009); however, the only statistically significant clinical variable independently associated with post-recurrence survival time was the proportion of patients undergoing complete cytoreductive surgery (p = 0.019). After controlling for all other factors, each 10% increase in the proportion of patients undergoing complete cytoreductive surgery was associated with a 3.0 month increase in median cohort survival time.

Conclusions

Among patients undergoing operative intervention for recurrent ovarian cancer, the proportion of patients undergoing complete cytoreductive surgery is independently associated with overall post-recurrence survival time. For this select group of patients, the surgical objective should be resection of all macroscopic disease.

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.

References (66)

  • V. Loizzi et al.

    Survival outcomes in patients with recurrent ovarian cancer who were treated with chemoresistance assay-guided chemotherapy

    Am J Obstet Gynecol

    (2003)
  • M.M. Leitao et al.

    Tertiary cytoreduction in patients with recurrent ovarian carcinoma

    Gynecol Oncol

    (2004)
  • B. Gronlund et al.

    Surgical cytoreduction in recurrent ovarian carcinoma in patients with complete response to paclitaxel-platinum

    Eur J Surg Oncol

    (2005)
  • M. Güngör et al.

    The role of secondary cytoreductive surgery for recurrent ovarian cancer

    Gynecol Oncol

    (2005)
  • O.W.S. Yap et al.

    Intraoperative radiation therapy in recurrent ovarian cancer

    Int J Radiation Oncology Biol Phys

    (2005)
  • A. Ayhan et al.

    The role of secondary cytoreduction in the treatment of ovarian cancer: Hacettepe University experience

    Am J Obstet Gynecol

    (2006)
  • C.W. Helm et al.

    Hyperthermic intraperitoneal chemotherapy in conjunction with surgery for the treatment of recurrent ovarian carcinoma

    Gynecol Oncol

    (2007)
  • A. Santillan et al.

    Secondary cytoreductive surgery for isolated nodal recurrence in patients with epithelial ovarian cancer

    Gynecol Oncol

    (2007)
  • A.R. Munkarah et al.

    Critical evaluation of secondary cytoreduction in recurrent ovarian cancer

    Gynecol Oncol

    (2004)
  • R.E. Bristow et al.

    Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: a meta-analysis

    Gynecol Oncol

    (2006)
  • H.R. Balvert-Locht et al.

    Improved prognosis of ovarian cancer in the Netherlands during the period 1975–1985: a registry-based study

    Gynecol Oncol

    (1991)
  • S.M. Eisenkop et al.

    Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial ovarian cancer: a prospective study

    Gynecol Oncol

    (1998)
  • Y. Ben-David et al.

    Meta-analysis comparing cisplatin total dose intensity and survival

    Gynecol Oncol

    (1995)
  • E.E. Voest et al.

    A meta-analysis of prognostic factors in advanced ovarian cancer with median survival and overall survival (measured with the log [relative risk]) as main objective

    Eur J Cancer Clin Oncol

    (1989)
  • G. Bolis et al.
  • A.N. Gordon et al.

    Long-term survival advantage for women treated with pegylated doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer

    Gynecol Oncol

    (2004)
  • A. Jemal et al.

    Cancer statistics 2008

    CA Cancer J Clin

    (2008)
  • J.V. Meigs

    Tumors of the female pelvic organs

    (1934)
  • C.T. Griffiths

    Surgical resection of tumor bulk in the primary treatment of ovarian carcinoma

    Natl Cancer Inst Monogr

    (1975)
  • W.J. Hoskins et al.

    The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma

    Am J Obstet Gynecol

    (1994)
  • R.E. Bristow et al.

    Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis

    J Clin Oncol

    (2002)
  • J.S. Berek et al.

    Survival of patients following secondary cytoreductive surgery in ovarian cancer

    Obstet Gynecol

    (1983)
  • R.E. Bristow et al.

    Secondary surgical cytoreduction for advanced epithelial ovarian cancer: patient selection and review of the literature

    Cancer

    (1996)
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