Histopathology predicts clinical outcome in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and 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.
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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.
References (21)
- et al.
Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in gynecological cancer
Int J Gynaecol Obstet
(2006) - et al.
What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)?
Gynecol Oncol
(2006) - et al.
An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical timeperiod as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy(NACT)
Gynecol Oncol
(2012) - et al.
Neoadjuvant chemotherapy in advanced ovarian cancer: on what do we agree and disagree?
Gynecol Oncol
(2013) - et al.
Cytoreductive surgery for ovarian cancer
Surg Clin North Am
(2001) - et al.
Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial ovarian cancer: a prospective study
Gynecol Oncol
(1998) - et al.
Histopathologic assessment of chemotherapy effects in epithelial ovarian cancerpatients treated with neoadjuvant chemotherapy and delayed primary surgical debulking
Gynecol Oncol
(2007) - et al.
Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy
Transl Oncol
(2012) - et al.
Platinum resistance after neoadjuvant chemotherapy compared to primary surgery in patients with advanced epithelial ovarian carcinoma
Gynecol Oncol
(2013) - et al.
Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis
J Clin Oncol
(2002)