Survival in Advanced-Stage Epithelial Ovarian Cancer Patients with Cardiophrenic Lymphadenopathy Who Underwent Cytoreductive Surgery: A Systematic Review and Meta-Analysis.

Malika Kengsakul,Christa D Niehot,Suwasin Udomkarnjananun,Stephen J Kerr,Gatske M Nieuwenhuyzen-De Boer,Heleen J Van Beekhuizen,Anna H J Bijleveld

doi:10.3390/cancers13195017

Abstract

Simple SummaryFavorable survival outcomes for patients with advanced-stage ovarian cancer are associated with complete cytoreduction. Enlarged cardiophrenic lymph node (CPLN) is commonly observed in advanced-stage epithelial ovarian cancer (AEOC); however, the prognostic impact of CPLN adenopathy is inconclusive. In this study, we evaluate the clinical outcomes of CPLN adenopathy in AEOC patients who underwent cytoreductive surgery. This systematic review and meta-analysis demonstrated that enlarged CPLN in preoperative imaging is highly associated with metastatic involvement. Patients with CPLN adenopathy had a significantly increased risk of recurrence of disease and dying from the disease in comparison to those without adenopathy, a finding likely related to more advanced disease in this group. Currently, there are no data that definitively demonstrate a therapeutic benefit of CPLN resection. Further randomized controlled trials should be conducted to definitively demonstrate whether CPLN resection at the time of cytoreductive surgery is beneficial.Purpose: To evaluate the clinical outcomes of enlarged cardiophrenic lymph node (CPLN) in advanced-stage epithelial ovarian cancer (AEOC) patients who underwent cytoreductive surgery. Methods: The Embase, Medline, Web of Science, Cochrane Library, and Google Scholar databases were searched for articles from the database inception to June 2021. Meta-analysis was conducted to determine the prognostic impact of surgical outcome, postoperative complication, and survival using random-effects models. Results: A total of 15 studies involving 727 patients with CPLN adenopathy and 981 patients without CPLN adenopathy were included. The mean size of preoperative CPLN was 9.1± 3.75 mm. Overall, 82 percent of the resected CPLN were histologically confirmed pathologic nodes. Surgical outcomes and perioperative complications did not differ between both groups. The median OS time was 42.7 months (95% CI 10.8–74.6) vs. 47.3 months (95% CI 23.2–71.2), in patients with and without CPLN adenopathy, respectively. At 5 years, patients with CPLN adenopathy had a significantly increased risk of disease recurrence (HR 2.14, 95% CI 1.82–2.52, p < 0.001) and dying from the disease (HR 1.74, 95% CI 1.06–2.86, p = 0.029), compared with those without CPLN adenopathy. CPLN adenopathy was significantly associated with ascites (OR 3.30, 95% CI 1.90–5.72, p < 0.001), pleural metastasis (OR 2.58, 95% CI 1.37–4.82, p = 0.003), abdominal adenopathy (OR 2.30, 95% CI 1.53–3.46, p < 0.001) and extra-abdominal metastasis (OR 2.30, 95% CI 1.61–6.67, p = 0.001). Conclusions: Enlarged CPLN in preoperative imaging is highly associated with metastatic involvement. Patients with CPLN adenopathy had a lower survival rate, compared with patients without CPLN adenopathy. Further randomized controlled trials should be conducted to definitively demonstrate whether CPLN resection at the time of cytoreductive surgery is beneficial.

Highlights

Ovarian cancer is the second leading cause of death among gynecological malignancies [1]
In our meta-analysis, we found that patients with cardiophrenic lymph node (CPLN) adenopathy had a significantly increased likelihood of having ascites, abdominal adenopathy, and extra-abdominal metastases, compared with patients without CPLN adenopathy
CPLN exceeding 7 mm in the short axis on CT or MRI scans, with a positive predictive value for detecting metastatic lesions of approximately 85%. Based on these lines of evidence, it would seem appropriate that patients with CPLN of this size should be considered candidates in future studies of the prognostic importance of CPLN dissection

Summary

Introduction

Ovarian cancer is the second leading cause of death among gynecological malignancies [1]. According to the International Federation of Gynecology and Obstetrics (FIGO), the majority of women with epithelial ovarian cancer (EOC) patients are initially diagnosed with advanced stage III and IV disease [2,3]. In 2014, FIGO published a new classification defining retroperitoneal lymph node metastasis between the inguinal ligament and the diaphragm as regional nodes, categorized as FIGO stage IIIA [7]. Extensive pelvic and paraaortic systematic lymphadenectomy procedures have been performed with the intention of removing potentially metastatic retroperitoneal lymph nodes. The randomized lymphadenectomy in patients with advanced ovarian neoplasm (LION) trial showed no benefit of systematic lymph node dissection in patients with radiologically unsuspicious nodes [8]

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