Cytoreductive surgery for advanced or recurrent endometrial cancer: A meta-analysis

Abstract

Objective

To determine the relative effect and quantify the impact of multiple prognostic variables on median overall survival time among cohorts of patients with advanced or recurrent endometrial cancer undergoing cytoreductive surgery.

Methods

Fourteen retrospective cohorts with advanced or recurrent endometrial cancer (672 patients) meeting study inclusion criteria were identified. Univariate analysis was used to assess the effect on median overall survival time of multiple variables. The limited number of studies available made multivariate analysis impractical.

Results

Statistically significant clinical variables associated with median overall survival time were the proportion of patients undergoing complete surgical cytoreduction, adjuvant radiation, or receiving adjuvant chemotherapy. Cohort median overall survival time was positively associated with increasing proportion of patients undergoing complete surgical cytoreduction (each 10% increase improving survival by 9.3 months, p = 0.04) and receiving post-operative radiation therapy (each 10% increase improving survival by 11.0 months, p = 0.004), while an increasing proportion of patients receiving chemotherapy was negatively associated with survival (each 10% increase decreasing survival by 10.4 months, p = 0.007).

Conclusions

The current analysis suggests that among patients with advanced or recurrent endometrial cancer, complete cytoreduction to no gross residual disease is associated with superior overall survival outcome. The unexpected correlation between treatment modality and survival may be a surrogate marker for more precise factors such as location of disease, performance status, or cytoreductive status post-operatively, which may have influenced the decision to administer adjuvant radiation versus chemotherapy and were not able to be controlled for given the limitations of the extracted data.

Introduction

The American Cancer Society has estimated that 40,000 women in the United States will be diagnosed with endometrial cancer in 2009, making it the most common gynecologic malignancy in the USA [1]. Fortunately, most women are diagnosed at an early stage and are treated by hysterectomy and surgical staging alone. Patients with advanced-stage endometrial cancer represent only 10-15% of all newly diagnosed cases but account for over half of all uterine cancer-related deaths [2], [3], with a survival rate as low as 5–20% for stage IV disease [4], [5], [6]. An effective treatment regimen has not been established for women with metastatic disease, and the majority of advanced-stage cancer patients will recur. Optimal management in women with advanced-stage or recurrent endometrial cancer is not well defined, but several retrospective studies have investigated the role of surgical cytoreduction in this setting.

Although the role of cytoreductive surgery in advanced and recurrent endometrial cancer is still somewhat controversial, its place in advanced ovarian cancer is well accepted as the standard of care [7]. After the landmark study by Griffiths [8] in 1975 demonstrated the inverse relationship between postoperative residual tumor size and overall patient survival, Hoskins et al. [9], as part of the Gynecologic Oncology Group (GOG), would go on to define “optimal cytoreduction” as a diameter of residual disease above which extensive efforts at cytoreduction do not improve survival, and furthermore that there is a continuum below this threshold, such that survival continues to improve with smaller volume of residual disease [10]. The survival benefit to surgical cytoreduction can be explained by a number of theories such as improvement of perfusion and drug delivery, decrease in adverse metabolic events to improve performance status, and reduction of viable tumor cells with potential for somatic mutations that can cause drug resistance [11], [12], [13].

Historically, the role of surgery in recurrent endometrial cancer was limited to candidates for total pelvic exenteration who had recurrence limited to the vaginal apex within a previously irradiated field [14], [15]. More recently, studies have sought to determine if there is a role for debulking surgery for patients who do not meet criteria for total pelvic exenteration. Articles solely looking at pelvic exenteration for recurrent endometrial cancer were not included because typically, exenteration is performed as a curative procedure. We were more interested in the value of cytoreductive surgery with more disseminated disease similar to the principles of advanced stage ovarian cancer and unlike recurrent cervical cancer. The existing literature investigating cytoreductive surgery for advanced or recurrent endometrial cancer is limited to small, non-randomized, retrospective studies. Given the survival benefit of surgical cytoreduction that has been clearly demonstrated in advanced ovarian cancer and the poor prognosis in patients with advanced or recurrent endometrial cancer, the objective of this study was to utilize meta-analysis to determine the relative effect and quantify the impact of multiple prognostic variables, including surgical cytoreduction, on median overall survival time among cohorts of patients with advanced or recurrent endometrial cancer undergoing cytoreductive surgery.