Elsevier

Gynecologic Oncology

Volume 105, Issue 3, June 2007, Pages 712-715
Gynecologic Oncology

The lack of significance of Ca125 response in epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and delayed primary surgical debulking

https://doi.org/10.1016/j.ygyno.2007.02.022Get rights and content

Abstract

Objectives.

To examine the prognostic significance of Ca125 response to neoadjuvant chemotherapy and delayed primary surgical debulking in epithelial ovarian cancer patients.

Methods.

Retrospective chart reviews were carried out from 1997 to 2005 to identify ovarian cancer patients treated with neoadjuvant chemotherapy. Ca125 response was defined as being a decrease of at least 50% from baseline assessment. Ca125 response was assessed in two phases: prior to surgical debulking to reflect the response to neoadjuvant chemotherapy and at the end of primary chemotherapy to assess the response to debulking surgery and further chemotherapy. Cox proportional hazard models were built to model progression-free intervals using predictor variables of: age, cancer stage, tumour grade, residual disease, and Ca125 response.

Results.

Ninety-one patients were included. About 83% had a positive Ca125 response following three cycles of neoadjuvant chemotherapy preoperatively. Cox regressions revealed two significant predictive variables of prolonged time to first progression: younger age (p = 0.002) and microscopic residual disease compared to suboptimal residual disease (p = 0.003). Ca125 response to neoadjuvant chemotherapy was not significantly predictive of progression-free survivals. The estimated median survival was 71.42 months (95% CI: 44.34–78.50) in patients with > 50% Ca125 decrease from surgery and further chemotherapy whereas in those with no response, the corresponding survival estimate was 44.02 months (95% CI: 33.26–54.79).

Conclusion.

The lack of Ca125 response from neoadjuvant chemotherapy is not an independent prognostic factor. All patients treated with neoadjuvant chemotherapy should undergo radical debulking surgery.

Introduction

Treatment of metastatic epithelial ovarian cancer includes a combination of aggressive surgical tumour debulking and combination platinum and taxanes-based cytotoxic chemotherapy [1], [2]. The optimal sequence of surgery and chemotherapy in the primary setting has not been established by prospective randomized trials comparing oncologic outcomes, patients' quality of life, and peri-operative morbidity and mortality. Traditionally, surgical exploration has been performed first to confirm the diagnosis and to maximally debulk metastatic disease based on retrospective data identifying minimal tumour residual postsurgery to be a strong prognostic indicator for improved prognosis and prolonged survival [3], [4], [5]. Even in patients who were initially suboptimally debulked, optimal interval surgical debulking after chemotherapy has been shown to be of further benefits [6]. Furthermore, in view of the results of a number of mature phase 3 studies, which support an added advantage of intraperitoneal chemotherapy over intravenous chemotherapy in optimally surgically debulked patients, the role of surgery in the primary setting is clear.

More recently, neoadjuvant chemotherapy prior to attempted surgical resection has been reported in a number of retrospective case series, where selected patients thought to be of poor surgical risk and/or not debulkable, to have comparable oncologic outcomes when compared to historical patient cohorts who were primarily surgically treated. Both groups of patients were treated with similar adjuvant chemotherapy peri-operatively. In patients treated with neoadjuvant chemotherapy, lower postoperative mortality, morbidity, and shorter postoperative hospital stays were observed [7], [8], [9], [10]. A current randomized phase 3 trial (EORTC protocol 55971) has recently completed accrual comparing the two treatment sequences. However, the final results are not expected for a few years while data is maturing. In patients treated with neoadjuvant chemotherapy, the best course of action is unclear when response to chemotherapy is deemed suboptimal after three or four cycles of treatment as Ca125 response during primary chemotherapy has been shown to be an independent prognostic factor in advanced ovarian cancer patients treated with primary surgery [11], [12], [13].

At our institution, based on the encouraging results of lower morbidities and equivalent oncologic outcomes in above referenced case series, a neoadjuvant chemotherapy approach with planned delayed primary surgical debulking was adopted since 1997. All patients treated with neoadjuvant chemotherapy were scheduled to undergo attempts at maximal surgical debulking regardless of the degree of response to chemotherapy followed by a further three or four more cycles of combination platinum taxane regimen. This have allowed us to explore the role of surgery in sub optimally responsive disease to neoadjuvant treatment. The objective of this study was to examine the impact of Ca125 response to neoadjuvant chemotherapy and delayed primary debulking surgery on time to first clinical recurrence and overall survival of advanced stage ovarian cancer patients.

Section snippets

Materials and methods

Retrospective chart reviews were carried out from 1997 to 2005 to identify epithelial ovarian cancer patients treated with neoadjuvant chemotherapy with primary intention to perform delayed surgical debulking. All included patients had an elevated Ca125 level at time of initial assessment. All borderline, stromal tumours, or germ cell tumours were excluded. All patients with unknown primary tumours were excluded including those with mucinous tumour of unknown origin. All pathology with

Results

Over this 7-year period, 130 patients with advance stage ovarian/primary peritoneal cancer were identified from the division of gynecologic oncology electronic ovarian cancer database. Out of this cohort, 91 patients with abnormal Ca125 levels who were started on neoadjuvant chemotherapy were identified, forming the current study population. In contrast to most other studies on neoadjuvant chemotherapy, none of our patients had major contraindications to primary surgery and 71% has no

Discussion

The current study examined in detail the pattern of Ca125 changes during neoadjuvant chemotherapy and after interval surgical debulking, followed by further chemotherapy in a group of epithelial ovarian/primary peritoneal cancer patients with no relative contraindication for initial surgical exploration. This minimizes the selection bias which exists in other reports where only poor surgical candidates are selected for a neoadjuvant approach [15], [16], [17]. We believe this represents a more

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