Retroperitoneal lymph node recurrence of epithelial ovarian cancer: Prognostic factors and treatment outcome

Highlights

• Treatment outcome and survival of patients with recurrent epithelial ovarian cancer by site of recurrence was evaluated

• Post relapse survival was significantly longer in the retroperitoneal vs. the intraperitoneal recurrence group.

• Retroperitoneal lymph nodes recurrence has a favourable prognosis with median survival longer than 5 years.

Abstract

Objective

To evaluate the treatment outcome and survival of patients with epithelial ovarian cancer recurrence isolated to the retroperitoneal lymph nodes compared to intraperitoneal spread.

Methods

A retrospective cohort study including women with recurrence of epithelial ovarian, cancer, who were treated at a single medical center, between 2000 and 2015. Patients were classified into three groups according to the site of recurrence: intraperitoneal only, retroperitoneal lymph nodes only, and both. Response to treatment was assessed by the RECIST criteria.

Results

Out of 135 patients in our cohort, 66 were diagnosed with intraperitoneal recurrence, 30 with retroperitoneal lymph node recurrence and 39 with combined site recurrence. The clinical, pathological and surgical characteristics were similar among all groups, besides CA-125 which was significantly lower in the retroperitoneal recurrence group at diagnosis, end of treatment and recurrence. The median follow-up period was 45.8 months. Overall survival (OS) and post relapse survival (PRS) were significantly higher in the retroperitoneal recurrence group vs. the intraperitoneal and combined site recurrence groups. (OS – 93.07, 47.9 and 41.7 months, respectively, p < .001, PRS – 68.57, 29.67 and 19.7 months, respectively, p < .001). On cox's regression analysis, retroperitoneal recurrence was found to be an independent prognostic factor for survival.

Conclusions

The site of recurrence has significant prognostic value regarding PRS and OS. Patients with recurrence limited to the retroperitoneal lymph nodes have a favourable prognosis with median survival longer than 5 years.

Introduction

Epithelial ovarian cancer (EOC) is the fourth most common cause of death in females. Every year 220,000 women develop EOC worldwide. Lack of reliable early detection method and late presentation at diagnosis contribute to the high mortality rate of ovarian cancer [1]. Treatment at presentation includes surgery and platinum-based chemotherapy. The desired surgical outcome in advanced stage disease is complete cytoreduction, i.e. no macroscopic disease at the end of surgery. These optimally debulked patients benefit a 60% five-year survival, compared to only 30% with a residual tumor of up to 1 cm at the end of the surgery [2]. Lymph node (LN) sampling is part of the staging procedure, and removal of enlarged or suspicious lymph nodes is important for cytoreduction, but systematic lymphadenectomy during primary debulking surgery does not improve overall survival [3]. When optimal debulking is not possible, neoadjuvant chemotherapy followed by interval debulking is acceptable [4].

Although most patients respond to treatment with platinum and taxane combination chemotherapy, many patients who present with advanced disease will experience recurrence within 18 months [5]. Most recurrences will be intra-abdominal, 13%–37% will involve intraperitoneal (IP) and retroperitoneal LN (RLN) metastases, and in 3–34% isolated LN recurrences are diagnosed, mostly para-aortic [[6], [7], [8], [9]]. Lymphatic spread was shown to be related to a more indolent course of disease. Patients with apparent stage I disease at diagnosis who were upstaged to stage IIIC due to RLN metastases, had a higher 5-year survival rate compared to patients with IP stage IIIC disease (58–84% and 18–36% respectively) [[10], [11], [12], [13]]. At recurrence, isolated RLN metastasis was also found to have favourable survival [7,8,[14], [15], [16]] especially if surgically resected during secondary cytoreduction [16,17]. However, a recently published study did not show survival benefit with secondary cytoreduction followed by chemotherapy compared to chemotherapy alone, in recurrent EOC, regardless of recurrence site [18].

LN recurrence, even if localized, is considered a systemic relapse and usually treated by chemotherapy. There is lack of data in the literature regarding the outcome of chemotherapy without secondary debulking in patients with different sites of recurrence. The aim of the present study is to compare response to chemotherapy and survival in patients with retroperitoneal versus intraperitoneal recurrence.