Prognostic Significance of Molecular Analysis of Peritoneal Fluid for Patients with Gastric Cancer: A Meta-Analysis

Abstract

BackgroundAccurately distinguishing serosal invasion in patients with gastric cancer (GC) prior to surgery can be difficult. Molecular analysis of peritoneal fluid (MAPF) for free cancer cells with higher sensitivity than other methods; however, its prognostic value for GC remains controversial, precluding its application in clinical practice.MethodsPubMed, EMBASE and other databases were systematically searched. Thirty-one studies were eligible for the meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled for overall survival (OS), disease-free survival (DFS) and peritoneal recurrence-free survival (PRF).ResultsThe current meta-analysis focused on patients with GC and negative cytological diagnoses. The results showed that positive MAPF status (MAPF+) led to poorer prognoses for OS (HR 2.59, 95% CI 1.99–3.37), DFS (HR 4.92, 95% CI 3.28–7.37) and PRF (HR 2.81, 95% CI 2.12–3.72) compared with negative MAPF status (MAPF-). Moreover, among the patients with GC who received curative treatment, the MAPF+ patients had poorer prognoses for OS (HR 3.27, 95% CI 2.49–4.29), DFS (HR 3.90, 95% CI 2.74–5.57) and PRF (HR 5.45, 95% CI 3.70–8.03). A meta-analysis of multivariate-adjusted HRs demonstrated that MAPF+ status was an independent prognostic factor for patients with GC who underwent curative treatment (OS: HR 2.19, 95% CI 1.47–3.28; PRF: HR 3.44, 95% CI 2.01–5.87). Using the identical target genes (CEA, CEA/CK20) as molecular markers, the patients with GC who were MAPF+ had significantly worse prognoses for OS (CEA: HR 3.03, 95% CI 2.29–4.01; CEA/CK20: HR 4.24, 95% CI 2.42–7.40), DFS (CEA: HR 3.99, 95% CI 2.24–7.12; CEA/CK20: HR 4.31, 95% CI 1.49–2.48) and PRF (CEA: HR 4.45, 95% CI 2.72–7.31; CEA/CK20: HR 6.46, 95% CI 3.62–11.55) than the patients who were MAPF-.Conclusion/SignificanceThe above results demonstrate that MAPF could be a prognostic indicator for patients with GC who have a negative cytological diagnosis and/or are receiving curative treatment. MAPF could provide clinicians with additional prognostic information that could aid in developing individualized treatment plans prior to surgery. The widely used target genes CEA, CEA/CK20 were confirmed to be valuable MAPF markers for predicting the prognosis of GC.

Prognostic value of CEA/CA72-4 immunohistochemistry in combination with cytology for detecting tumor cells in peritoneal lavage in gastric cancer

“…Thus, finding novel and useful biomarkers to improve the efficiency for detecting peritoneal metastasis is very important 18 . Beside peritoneal cytology, genetic detection of CEA 19 , CK20 (CK20: cytokeratin 20) 20 , CK19 (CK19: cytokeratin 19) 21 , and MAGE (MAGE: melanoma-associated gene) 22 using RT-PCR (RT-PCR: reverse transcriptase-polymerase chain reaction) were reported as one of available tools that correlated with patients' metastasis. Moreover, immunohistochemistry of cells from peritoneal lavage is considered another available strategy for directly detecting metastatic tumor cells.…”

Advanced gastric cancer: new perspectives of treatment

“…The 5-year survival is less than 3% and the overall mean and median survival are of 6.5 (range, 0.1-48.0) and 3.1 months, respectively. 28,29 PC from GC has for sure a better prognosis than PC from pancreatic cancer (overall mean and median survival times of 2.9 and 2.1 months respectively), but worse than PC from colorectal carcinoma (overall mean and median survival times of 6.9 and 5.2 months, respectively). 29 The 5-year survival of patient with AGC and FPTCs has been reported to be almost the same as that of those with disseminating metastasis to the adjacent peritoneum of the stomach (15.3 and 14.8% respectively).…”

Utility of molecular analysis of peritoneal fluid in staging laparoscopy of advanced oesophagogastric junction and gastric cancer prior to neoadjuvant treatment

“…Regarding the method to analyse the presence of cells in the peritoneal uid, most authors use citology (Papanicolaou stain) despite having a highly variable sensitivity of between 11-67% [7][8][9][10]. There are other techniques such as molecular analysis of peritoneal uid using reverse transcriptase-polymerase chain reaction (RT_PCR) of proteins including carcinoembryonic antigen (CEA) or cytokeratin 20 (CK20), which have shown a higher sensitivity in some series [9][10][11][12] (up to 77% [13][14]). However, the prognostic value of this technique is controversial [9,12] especially in patients who are Cyt-but RT_PCR+, and molecular analysis was not included in their therapeutic algorithms.…”