RT-PCR Increases Detection of Submicroscopic Peritoneal Metastases in Gastric Cancer and Has Prognostic Significance

Positive peritoneal cytology confers the same prognosis as clinical stage IV disease in gastric cancer. Conventional cytology examination, however, has low sensitivity. We hypothesize that real-time polymerase chain reaction (RT-PCR) may have increased sensitivity and provide more accurate staging information.

From February 2007 to April 2009, peritoneal lavage samples were collected prospectively from 156 patients with biopsy-proven gastric cancer undergoing staging laparoscopy. These washings were analyzed by both Papanicolaou staining and RT-PCR for the tumor marker carcinoembryonic antigen (CEA).

Visible peritoneal disease was seen at laparoscopy in 38 patients (LAP+, 24%). Cytology was positive (CYT+) in 23 patients, while RT-PCR was positive (PCR+) in 30. The sensitivity of CYT for the detection of visible disease was 61% compared to 79% for PCR (P = 0.02). No visible peritoneal disease was seen at laparoscopy (LAP−) in 118 (76%) patients. Eight (7%) were CYT+, while 28 (24%) were PCR+. Predictors of PCR positivity included advanced-stage disease (T3–4 vs. T1–2 tumors) and poor pathologic features such as vascular or perineural invasion. Long-term follow-up demonstrated a worse survival of LAP−CYT−PCR+ (P = 0.0003) and LAP−CYT+PCR+ (P = 0.0004) compared to LAP−CYT−PCR− patients. There was no significant difference in survival between CYT−PCR+ and CYT+PCR+ patients. PCR positivity also predicted a higher likelihood of disease recurrence after resection. An R0 resection was performed in 85 LAP− patients (54%): only 1 (1%) was CYT+, while 13 (15%) were PCR+. Of this group, PCR+ demonstrated a worse survival than PCR− patients (P = 0.02). Further analysis showed that, in R0 resection, stage III/IV, CYT− subgroup, PCR+ was associated with a trend towards worse survival (P = 0.09) compared to PCR− patients.

RT-PCR for CEA increases the detection of subclinical peritoneal disease and is more sensitive than cytology. Predictors of positive PCR included advanced-stage disease, vascular invasion, and perineural invasion. PCR positivity was associated with increased disease recurrence and decreased survival. Further follow-up is required to determine if PCR positivity alone is an independent predictor of poor survival in gastric cancer.