Maximal Cytoreduction May Be of Merit in Advanced/Recurrent Endometrial Cancer
Abstract & Commentary
By Robert L. Coleman, MD, Professor, University of Texas; M.D. Anderson Cancer Center, Houston, is Associate Editor for OB/GYN Clinical Alert.
Dr. Coleman reports no financial relationship to this field of study.
Synopsis: surgical cytoreduction in women with advanced or recurrent endometrial cancer was associated with improved overall survival (OS). Each 10% increase in tumor cytoreduction was associated with 9.3 months gain in OS. Like ovarian cancer, cytoreduction to microscopic disease appears to be a reasonable goal in medically fit patients.
Source: Barlin JN, et al. Cytoreductive surgery for advanced or recurrent endometrial cancer: A meta-analysis. Gynecol Oncol 2010;118:14-18.
Patients with evidence of metastatic endometrial cancer are typically considered for surgical debulking to establish a diagnosis, reduce tumor burden, and plan adjuvant therapy. The value of the extent to which this is carried out is not well described. Since much of the existing data comes from small retrospective series, a meta-analysis was conducted to examine more closely the prognostic and therapeutic impact that surgical cytoreduction has on this condition. The authors identified 14 studies where at least one cohort underwent surgery for cytoreduction and where the outcomes in those meeting the study definition of "optimal" vs "suboptimal" were compared. From these reports, 672 patients were eligible for analysis. Three variables were associated with OS: proportion of patients with complete surgical cytoreduction, adjuvant radiation, and adjuvant chemotherapy. The former two were positively associated with outcome with each 10% increase in proportion associated with 9.3-month (cytoreduction) and 11.0-month (radiation) increases in OS. Each 10% increase in the proportion of patients receiving chemotherapy was associated with a 10.4-month decrease in OS. Noting the obvious limitations to a meta-analysis of all retrospective reports, the analysis supports aggressive efforts to surgically reduce tumor bulk. The disparate associations of adjuvant therapy use may have been biased by disease status, debulking status, performance status, and location of disease following surgery.
Commentary
It is remarkable that while only 10%-15% of all endometrial cancer patients have metastatic disease at presentation, they account for more than 50% of the deaths due to disease. In addition, rare histology, such as clear cell and serous cancer, are more frequently associated with metastatic disease on presentation and are more commonly identified in elderly and more infirm patients. All patients with metastatic or recurrent disease deserve consideration of adjuvant therapy. However, the intensity and type of this treatment must take into account the medical performance of the patient, prior or existing toxicities, and the distribution of disease. These factors are important to consider when reviewing a paper such as the current one, in which healthier patients with small volume or localized disease are more likely to receive aggressive surgery and postoperative localized treatment. The inherent bias from case selection in retrospective series cannot be overcome by increasing the sample for meta-analysis. This is highlighted by the disparate impact on outcome by treatment modality: radiation vs chemotherapy. When this question was asked in a large prospective randomized clinical trial in a similar patient population, chemotherapy was found to have a superior impact on OS vs radiation therapy. The bulk of this effect was seen in patients with stage IV disease where radiation is problematic for controlling macroscopic tumor residuum.
Two other caveats should be considered in the current analysis. First, several randomized clinical trials assessing the impact of adjuvant therapy have been conducted but were not included. Each of these study's eligibility criteria required documentation of stage and many required postoperative surgical residuum prior to randomization. The analysis would be more robust if these data could have been retrieved. Second, recurrent disease patients represent a very heterogeneous cohort, which may be confounded by prior therapy, prior surgery, and performance status.
Overall, the conclusions do make some sense because endometrial cancer is a disease where adjuvant therapy has independent clinical efficacy. It is because of this primary feature that surgery could leverage some impact on outcome. However, until a randomized trial can be conducted to address the issue prospectively, as was recently done in ovarian cancer, we will be left to speculate.
Patients with evidence of metastatic endometrial cancer are typically considered for surgical debulking to establish a diagnosis, reduce tumor burden, and plan adjuvant therapy.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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