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SAN FRANCISCO -- Extensive intraoperative peritoneal lavage (EIPL) failed to improve survival in patients with resectable gastric cancer, results of a large Japanese study showed.

Patients who underwent EIPL had a 3-year disease-free survival (DFS) of 63.9% versus 59.7% for patients who had surgery without EIPL. The 5-year DFS was 58.0% and 51.9% with and without EIPL, respectively. Neither difference achieved statistical significance, according to Yasuhiro Kodera, MD, of Kyoto University, and colleagues.

Overall survival (OS) also did not differ significantly between treatment groups at 3 or 5 years, Kodera reported here at the Gastrointestinal Cancers Symposium (GICS).

"The primary endpoint of disease-free survival, designed on the basis of a previous small-scale trial, was not met," said Kodera. "EIPL exhibited a trend toward decreased cancer recurrence among patients who had intra-abdominal surgical site infections (SSIs)."

Even if the trial had shown a survival benefit with EIPL, the impact on clinical practice in North America would have remained unclear, as intraperitoneal therapy is fairly uncommon the management of gastrointestinal (GI) cancers, said Jeffrey Meyerhardt, MD, a GI cancer expert for the American Society of Clinical Oncology.

"It has been studied in gastric cancer in multiple other studies, some of which evaluated different strategies, including heated chemotherapy, but this is the first large, randomized trial to evaluate the concept in gastric cancer, and it was negative. That's good to know," Meyerhardt, of Dana-Farber Cancer Institute in Boston, told 名媛直播.

"What's more common is the situation involving a patient with known peritoneal disease at the time of surgery -- and limited to the peritoneum -- and they do surgery to remove it and then give chemotherapy. Whether that can improve outcomes or disease control is still pretty much unknown because there have been no randomized trials."

Peritoneal dissemination is associated with poor prognosis in patients with resectable gastric cancer. A from another group in Japan showed significant improvement in 5-year survival for patients who underwent EIPL for circulating free cancer cells but not overt peritoneal metastases in association with resectable gastric cancer.

The trial also showed a peritoneal recurrence rate exceeding 80% in patients who had surgery and conventional intraperitoneal lavage, reduced to 40% in patients who underwent EIPL. Investigators in the trial subsequently advocated for EIPL as a standard prophylactic strategy to clear the peritoneal cavity of circulating tumor cells and prevent peritoneal recurrence after surgery for gastric cancer, said Kodera.

The findings provided the basis of a phase III randomized trial involving 314 patients with resectable gastric cancer. All patients underwent advanced cancer dissection and were randomized to standard intraperitoneal lavage or EIPL. In the non-EIPL arm, surgeons irrigated the intraperitoneal cavity with 3,000 mL of saline. In the EIPL group, a 10,000 mL lavage was performed.

Subsequent treatment in both arms was based on disease stage. Patients with stage I disease received no further treatment. Patients with stage II or III cancer received a 12-month course of the oral fluoropyrimidine S-1, and patients with stage IV were treated with the physician's choice of therapy.

The primary endpoint was 3-year DFS, and the primary analysis included 295 patients. Demographic and clinical characteristics (including pathologic findings) did not differ significantly between patients. The overall incidence of surgical complications was 27.3% in the non-EIPL group and 20.0% in the EIPL arm, including intraabdominal surgical site infections in 12.7% and 10.3% respectively.

The difference in 3-year DFS represented an 18% reduction in the hazards ratio in favor of EIPL, but did not achieve statistical significance (95% CI 0.57-1.16, P=0.25). The between-group difference increased by year 5 but still did not reach statistical significance. OS at 3 years was almost the same between groups (HR 0.91, 95% CI 0.60-1.37, P=0.65). Peritoneal-recurrence-free survival also did not differ between groups at 3 years (72.3% versus 69.7%, HR 092, 95% CI 0.62-1.36, P=0.65).

Subgroup analysis showed no consistent advantage favoring EIPL. However, investigators noted a substantial improvement in DFS in the small subgroup (n=34) of patients with had grade ≥2 intra-abdominal SSIs: 80.0% versus 47.4% at 3 years and 68.6% versus 47.4% at 5 years. Patients free of such complications did not have a DFS benefit with EIPL.

Elaborating on the SSI findings, Kodera said inflammation and other factors associated with infection might facilitate the formation of intraperitioneal metastases from circulating tumor cells. However, since EIPL eliminated the circulating cells, investigators had no ready explanation for the observation.

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