Elsevier

Gynecologic Oncology

Volume 131, Issue 3, December 2013, Pages 531-534
Gynecologic Oncology

Histopathology predicts clinical outcome in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and debulking surgery

https://doi.org/10.1016/j.ygyno.2013.09.030Get rights and content

Highlights

  • We investigate the prognostic factors for advanced ovarian cancer patients treated with neoadjuvant chemotherapy followed by interval debulking surgery.

  • Patients received neoadjuvant chemotherapy every 3 weeks for three to four cycles, followed by interval debulking surgery.

  • The amount of residual disease, stage, and the presence of more viable disease in operative specimens are prognostic factors.

Abstract

Objective

To analyze the factors prognostic of survival in patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery.

Methods

Outcomes were retrospectively in patients with advanced EOC or peritoneal cancer who received neoadjuvant paclitaxel and carboplatin chemotherapy every 3 weeks for three to four cycles, followed by interval debulking surgery and three additional cycles of the same regimens from January 2001 to November 2010. Therapeutic response was assessed histopathologically as grade 0 to 3, based on the degree of disappearance of cancer cells, displacement by necrotic and fibrotic tissue, and tumor-induced inflammation. Factors prognostic of progression-free survival (PFS) and overall survival (OS) were calculated.

Results

The 124 enrolled patients had a median age of 62 years (range, 35–79 years). Viable cancer cells were observed in specimens resected from 72 patients (58%) at interval debulking surgery after NAC. Multivariate analysis using the Cox proportional hazard model showed that advanced (stage IV) disease (hazard ratio [HR] = 1.94, p = 0.003), residual cancer at the end of surgery ≥ 1 cm (HR = 3.78, p < 0.001), and histological grade 0–1 (HR = 1.65, p = 0.03) were independent predictors of decreased OS. Grade 0–1 was also an independent predictor of increased risk of relapse within 6 months (odds ratio = 8.42, p = 0.003).

Conclusions

Residual disease of ≥ 1 cm, advanced stage, and the presence of more viable disease in resected specimens are prognostic factors for survival in advanced EOC patients receiving NAC followed by interval debulking surgery.

Introduction

Ovarian cancer is a gynecologic malignancy with a high mortality rate. In Japan, morbidity rates due to ovarian cancer have increased over the past decade. Approximately 70% of women with ovarian cancer are diagnosed at an advanced stage of disease, at which time they have already experienced peritoneal dissemination [1]. Primary debulking surgery (PDS) followed by platinum-based chemotherapy is the standard treatment for ovarian cancer patients, and complete debulking is the only factor significantly prognostic of survival [2], [3], [4]. However, complete resection is difficult for patients with massively disseminated tumors.

Neoadjuvant chemotherapy (NAC) has been shown to benefit patients with advanced epithelial ovarian cancer (EOC). For example, a recent randomized trial, performed by the European Organization for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada (NCIC), comparing PDS with NAC followed by interval debulking surgery, found that, although progression-free survival (PFS) and overall survival (OS) rates were similar in the two groups, adverse effect and mortality rates were significantly lower in the NAC group [5]. Thus, NAC before radical surgery has become a primary treatment for patients with advanced EOC [6], [7]. However, despite NAC being useful for patients in whom optimal debulking appears impossible, primary surgical cytoreduction should not be precluded by a lack of surgical skills and experience [8], [9]. NAC in patients with large tumors may also lead to the development of drug resistance, resulting in shorter PFS and OS. Therefore, it is necessary to distinguish patients who can benefit from primary surgical cytoreduction with those who can benefit from NAC followed by interval debulking surgery. We have therefore analyzed the factors prognostic for OS and PFS in patients with advanced EOC treated with NAC followed by interval debulking surgery, and assessed the likelihood of developing drug resistance by histological assessment of surgical specimens after NAC.

Section snippets

Materials and methods

Patients with advanced stage EOC or peritoneal (FIGO Stage IIIc and IV) treated in the Department of Gynecologic Oncology at Hyogo Cancer Center from January 2001 to November 2010 were retrospectively analyzed. A total of 220 patients were clinically diagnosed with stage IIIc and IV EOC or peritoneal cancer by imaging modalities, including abdominal and pelvic computed tomography (CT) scan or magnetic resonance imaging (MRI). Primary EOC or peritoneal cancer was definitively diagnosed by

Results

The characteristics of the 124 included patients are shown in Table 1. Median follow-up was 33 months (range, 3–143 months). Twenty-six (21%) patients had other histological diseases, because histological identification was difficult owing to cellular inflammation after NAC. Surgery was optimal in 104 (83.9%) patients, defined as residual tumor < 1 cm. Evaluation of the resected specimens showed histological Grade 0 or 1 in 72 (58.1%) patients, indicating poor responsiveness, with persisting

Discussion

Maximal primary cytoreductive surgery is the standard treatment for patients with advanced EOC, with the amount of residual tumor associated with patient prognosis [13], [14]. NAC has been introduced to treat patients unable to undergo complete resection during in PDS. The EORTC–NCIC randomized trial showed that a largest residual tumor less than 1 cm was achieved in 41.6% of patients after primary debulking and in 80.6% of patients after interval debulking. However, NAC did not improve OS.

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Acknowledgment

We thank Ms Ushio and Ms Kinoshita for their excellent technical assistance.

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