Prognostic value of circulating tumor cells and disseminated tumor cells in patients with ovarian cancer: a systematic review and meta-analysis
Cui et al. Journal of Ovarian Research
Prognostic value of circulating tumor cells and disseminated tumor cells in patients with ovarian cancer: a systematic review and meta-analysis
Long Cui 0
Joseph Kwong 0
Chi Chiu Wang 0
0 Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hongkong , Shatin, Hong Kong , China
Recent studies have shown diagnostic and prognostic values of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in various cancers, including ovarian cancer. We aimed to evaluate the association of CTCs and/ or DTCs with the clinical outcomes of ovarian cancer. Clinical studies of CTCs/DTCs of ovarian cancer were included for systematic review and meta-analysis. A total of 236 studies were screened but only 16 qualified studies with 1623 subjects were included. Odds ratio (OR) showed CTCs/DTCs were not significantly associated with serous carcinoma (OR = 0.71 [0.49, 1.05]), lymph node metastasis (OR 1.14 [0.67, 1.93]), and residual disease (OR 1.45 [0.90, 2.34]); but significantly associated with advanced tumor staging (OR = 1.90 [1.02, 3.56]). The overall pooled hazard ratio (HR) of CTCs/DTCs on OS and PFS/DFS was 1.94 [1.56- 2.40] and 1.99 [1.59-2.50], respectively. Subgroup analyses revealed that CTCs were significantly associated OS (HR 1.97 [1.50-2.58]) and PFS/DFS (HR 2.52 [1.83-3.48]), while DTCs was significantly associated OS (HR 1.89 [1.33, 2.68]) and PFS/DFS (HR 1.60 [1.17, 2.19]). Meta-analysis showed strong relationship of CTCs/DTCs with advanced staging, treatment response and poor prognosis in patients with ovarian cancer.
Ovarian cancer; Circulating tumor cells; Disseminated tumor cells; Prognosis
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Introduction
Ovarian cancer is the most frequent cause of death
amongst gynecological cancers worldwide. Majority of
cases diagnosed in late stage of the disease and resulted
in poor survival [1]. The five-year survival rate of
patients with ovarian cancer is only around 30 % in
Stage III or IV [2]. The reasons of delayed diagnosis are
partly due to lack of sensitive signs and symptoms and
effective screening methods [3]. Although survival has
been improved with the use of cyto-reduction surgery
along with platinum- and/or taxane-based chemotherapy,
nearly 80 % eventually relapse within 5 years [4].
Therefore, methods that help detection of ovarian cancer in
early stage and monitoring of tumor progression have
great potential to improve survival of the patients.
It was considered that ovarian cancer spreads primarily
through direct dissemination in the abdominal cavity.
While the presence of disseminated tumor cells (DTCs) in
bone marrow of patients with ovarian cancer have been
reported [5, 6]. However, bone marrow sampling is rather
an invasive procedure, which is not widely accepted in the
clincial management. In recent years, focus has been
shifted to the detection of circulating tumor cells (CTCs)
in peripheral blood. CTCs are tumor cells release from the
primary tumor and then circulate through the
bloodstream, resulting in spreading to different organs and
subsequent outgrowth of the tumor cells in new
microenvironment. These CTCs thereby have the
potential to contribute to the development of local and
systematic relapses [7]. Either DTCs or CTCs have potential to
predict prognosis and to monitor treatment efficacy in
cancer patients. Presence of CTCs has been reported in
several solid tumors, including breast [8], colorectal [9],
lung [10], kidney [11], esophageal [12], liver [13], prostate
[14], and pancreatic cancers [15, 16]. Studies of CTCs/
DTCs in ovarian cancer patients had been investigated,
most of them demonstrated that CTC or DTC is
associated with poor clinical outcome [17–22]. However, other
studies failed to show the positive correlation [5, 23, 24]
and even demonstrated negative association in terms of
progression free survival/disease free survival (PFS/DFS)
and overall survival (OS) [25, 26]. The prognosis value of
CTCs/DTCs in ovarian cancer remains controversial. A
recent systematic review of CTCs and DTCs in ovarian
cancer concluded the association of CTCs and DTCs with
adverse clincopathological characteristics and poor clinical
outcomes [27], but no appropriate statistics and detailed
analysis were provided.
The objective of this study was to conduct a
metaanalysis of published clinical studies of CTCs/DTCs in
ovarian cancer and to investigate the association of CTCs/
DTCs with clinical outcomes.
Methods
An independent systematic review of the literature across
PubMed and EMBASE database was conducted on April
27, 2015. The search strategy included keywords such as
“ovarian cancer”, “ovarian carcinoma”, “circulating tumor
cell (s)”, “disseminated tumor cell (s)”, and “prognos*”.
Only studies published in peer reviewed journals were
included, data from letters and conference abstracts were
not included. The study selection process is shown in
Fig. 1 and search strategies and results are pro (...truncated)