Prognostic significance of peritoneal lavage cytology in staging gastric cancer: systematic review and meta-analysis
Prognostic significance of peritoneal lavage cytology in staging gastric cancer: systematic review and meta‑analysis
Sara Jamel 0
Sheraz R. Markar 0
George Malietzis 0
Amish Acharya 0
Thanos Athanasiou 0
George B. Hanna 0
0 Department of Surgery and Cancer, Imperial College London, 10th Floor QEQM Building, St Mary's Hospital , South Wharf Road, London W2 1NY , UK
1 George B. Hanna
Background Peritoneal cytology has been used as a part of the cancer staging of gastric cancer patients. The primary aim of this systematic review was to evaluate the value of peritoneal cytology as part of the staging of gastric cancer and survival prediction. The second aim was to establish if positive cytology may be modified by neoadjuvant therapy, to improve prognosis. Methods An electronic literature search was performed using Embase, Medline, Web of Science, and Cochrane library databases up to January 2016. The logarithm of the hazard ratio (HR) with 95% confidence intervals (CI) was used as the primary summary statistic. Comparative studies were used, and the outcome measure was survival in three groups: (1) positive versus negative cytology at staging laparoscopy immediately preceding surgery; (2) effect of neoadjuvant therapy on cytology and survival; and (3) positive cytology in the absence of macroscopic peritoneal disease was compared with obvious macroscopic peritoneal disease. Results Pooled analysis demonstrated that positive cytology was associated with significantly reduced overall survival (HR, 3.46; 95% CI, 2.77-4.31; P < 0.0001). Interestingly, negative cytology following neoadjuvant chemotherapy was associated with significantly improved overall survival (HR, 0.42; 95% CI, 0.31-0.57; P < 0.0001). The absence of macroscopic peritoneal disease with positive cytology was associated with significantly improved overall survival (HR, 0.64; 95% CI, 0.56-0.73; P < 0.0001).
Gastric cancer; stomach neoplasm; Laparoscopy; Peritoneal cytology; Cancer staging; Cancer prognosis
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Conclusion This study suggests that patients with initial
positive cytology may have a good prognosis following
neoadjuvant treatment if the cytology results change to negative
after treatment.
Introduction
The main treatment of advanced nonmetastatic gastric
cancer is surgical resection with perioperative chemotherapy
or chemoradiotherapy [
1, 2
]. Efforts to prolong survival in
metastatic gastric cancer have showed little improvement [
1,
2
]. Accurate staging of gastric cancer is crucial in selecting
the appropriate treatment option, whether curative or
palliative. The Japanese Gastric Cancer Association included the
results of cytological examination of peritoneal lavage fluid
as a key prognostic factor in their classification of gastric
carcinoma [
1, 3
]. However, recently published guidelines
suggested that cytology-positive status in the absence of
other noncurative factors, that is, macroscopic disease, can
be managed with D2 gastrectomy and perioperative
chemotherapy [4]. Initial data of those treated with surgery alone
showed poor 5-year survival; however, more recent
publications have shown that the use of postoperative chemotherapy
improves overall survival rates to 26%, [
5, 6
]. On the other
hand, if the information on cytology status were available
before surgery, a chemotherapy-first strategy could be taken
whereby patients whose cytology status turned negative
could be preferentially treated with curative surgery [
7, 8
].
The incidence of positive peritoneal cytology for patients
with gastric cancer varies, in published reports, from 4% to
41% [
9
]. Peritoneal washings positive for cancer cells have
been demonstrated to correlate with the extent of cancer (T1/
T2, 0%; T3/T4, 10%; M+, 59%) [
10
] and have been
considered as stage IV disease [
11
]. The influence of positive
cytology on survival has been shown as a powerful independent
predictor of survival when compared to other postoperative
pathological variables such as the tumor serosal invasion or
lymph node involvement [
2, 6, 12, 13
]. Positive cytology
was shown to be the most powerful predictor of outcome,
with a risk ratio of 2.7 for patients undergoing curative
resection [2]. Furthermore, studies have also shown that the
number and arrangement of cytology-positive cells have an
effect on survival at the time of gastrectomy [
10, 12
].
The results of the randomized controlled trial by the apan
Clinical Oncology Group (JCOG 0705) and Korea Gastric
Cancer Association (KGCA01), comparing gastrectomy
plus chemotherapy versus chemotherapy alone in advanced
gastric cancer with a single noncurable factor, showed no
advantage of resecting the primary gastric cancer in the
presence of peritoneal metastasis [
11
]. Nevertheless, the
treatment recommendations for gastric cancer in the event
of positive cytology range from palliative chemotherapy to
attempts at neoadjuvant therapy followed by surgical
resection [
4, 14
].
The aim of this study w (...truncated)