| Site | Grade I recommendations | Grade II recommendations | Grade III recommendations |
|---|---|---|---|
| Patients with only positive peritoneal cytology (cy1P0) | Systemic chemotherapy ± molecular targeted therapy ± intraperitoneal chemotherapy or encourage participation in clinical trials (Evidence 2A) | Radical surgery if conversion to cy0 after conversion therapy b (Evidence 2B) |
Standard D2 surgery followed by adjuvant chemotherapy c (Evidence 2B) |
| Patients with only gross peritoneal metastasis (P1) | Refer to late‐stage gastric cancer treatment or recommend participation in clinical trials | Systemic chemotherapy ± molecular targeted therapy ± intraperitoneal chemotherapy or encourage participation in clinical trials f (Evidence 2A) | For potentially resectable tumors who turned CR/PR and CY(‐) after conversion therapy, palliative surgery can be considered d (Evidence 2B) |
| Patients with gross peritoneal and other organ metastasis e | Refer to late‐stage gastric cancer treatment or recommend participation in clinical trials |
Abbreviations: cy, cytologic results of peritoneal lavage.
Notes
Gastric cancer with peritoneal metastasis can be divided into two types: Type 1, only positive peritoneal cytology for cancer cells in the abdominal cavity, without gross metastasis, and these can be further classified as the presence of cancer in the cytologic results of peritoneal lavage (CY1) absence of local peritoneal metastatic nodules (P0); Type 2, visible gross peritoneal metastases in the abdominal cavity, which can be recorded as P1 [210].
Compared with CY0P0, CY1P0 gastric cancer is a stage IV gastric cancer that is technically considered operable but biologically considered unresectable with poorer overall prognosis [211]. At present, the initial treatment for patients with CY1P0 tumors is systemic chemotherapy unless they are symptomatic and require surgery.
A systematic review including 21 studies, which comprised 6499 patients, was conducted to evaluate the role of peritoneal cytology as a predictor of staging and survival of gastric cancer and whether positive cytology can improve the prognosis through neoadjuvant therapy [212]. The results showed that negative cytology after neoadjuvant therapy was associated with significant improvement in OS (HR: 0.64, 95% CI: 0.56‐0.73, P < 0.0001). Intraoperative peritoneal chemotherapy (IPC) and extensive intraoperative peritoneal lavage (EIPL) have also been shown as effective treatments. Results of a meta‐analysis showed that, compared with surgery alone, surgery combined with IPC could improve the 5‐year survival rate (risk ratio [RR] = 3.10) and reduce the risk of recurrence (odds ratio [OR] = 0.45), while IPC combined with EIPL could further increase the above benefits (corresponding RR = 6.19, OR = 0.13) [213]. For CY1P0 patients, multidisciplinary comprehensive treatment using hyperthermic intraperitoneal perfusion chemotherapy (HIPEC)/peritoneal lavage combined with surgery and systemic chemotherapy has been explored in many centers. In Japan, these patients are more likely to receive preoperative IPC combined with radical D2 gastrectomy [214]. However, due to inconsistencies in patient selection, treatment types (palliative or radical), surgical techniques, usage of intraperitoneal chemotherapy, as well as systemic chemotherapy drug selection, the results of such treatments remain inconsistent. Overall, for CY+P0 patients, preliminary results of the exploratory study suggest that systemic chemotherapy has the possibility of converting the positive cytology of CY1P0 to negative and can improve the outcome. However, the significance and indications of gastrectomy for patients whose cytology turned from positive to negative are still inconclusive. For such cases, chemotherapy should be prioritized before surgery, and after repeated confirmation of CY0P0 diagnosis by laparoscopic exploration, resection of the primary lesion can be considered.
There are few randomized controlled studies focused on gastric cancer with positive exfoliative cytology. The CCOG0301 study [215] suggests radical gastrectomy followed by adjuvant S‐1 chemotherapy for CY1P0 patients. According to the result of a report [216], radical surgery combined with S‐1 monotherapy in solitary CY1P0 patients can increase their mOS to 22.3 months.
For patients with only gross peritoneal metastasis, chemotherapy has been associated with shrinking or reducing the number of peritoneal metastases, but it is difficult to eliminate all micrometastases with chemotherapy, even if the initial response is satisfactory [217, 218]. When peritoneal metastases have responded well to chemotherapy, the primary tumor and/or metastases can be considered for resection. Since most of these cases recur in the abdominal cavity after surgery, it is defined as cytoreductive surgery or tumor reduction surgery.
For gastric cancer patients with gross peritoneal and other organ metastasis, palliative chemotherapy remains the first choice. Conversion therapy can only be considered in a small number of patients, and the possibility of R0 resection depends mainly on the response to first‐line chemotherapy. For those with gastrointestinal bleeding and/or obstruction, palliative surgery such as primary tumor resection and/or bypass surgery can be considered [219].
The palliative treatment recommendations for patients with peritoneal metastasis can be referred from the late‐stage treatment of gastric cancer or consider participation in clinical trials. Drainage of ascites and intraperitoneal perfusion chemotherapy can be considered for patients with symptomatic abdominal pain. The PHOENIX‐GC study compared intraperitoneal and intravenous paclitaxel plus S‐1 versus cisplatin plus S‐1 in gastric cancer patients with peritoneal metastasis and showed that although no significant improvement in OS in the overall population was observed, patients with moderate to severe ascites had some survival benefits [220].