Clinical outcomes of conversion surgery following immune checkpoint inhibitors and chemotherapy in stage IV gastric cancer with peritoneal metastasis.

Abstract

281 Background: Although anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy has shown promising antitumor activity in advanced gastric adenocarcinoma (GC), the evidence of conversion therapy for initially GC with peritoneal metastasis is limited. This study aimed to clarify the clinical outcomes of conversion therapy for such patients. Methods: In this retrospective single institution cohort study, we analyzed 83 GC patients with peritoneal metastasis who received first-line anti-PD-1 antibody and chemotherapy and/or target therapy (trastuzumab) between November 2019 and June 2023. In patients who respond well to treatment, when preoperative imaging studies, multidisciplinary team discussions, and staged laparoscopy indicated the absence of peritoneal metastasis and the possibility of R0 resection, patients were offered conversion surgery. In this study, palliative surgery was not included. Patients were divided into two groups: conversion therapy group and palliative therapy group. Results: All patients underwent staging laparoscopy at their initial visit and underwent at least 2 treatment cycle, with a median follow-up time of 20.3 (16-24.6) months. Of the 83 patients, 32 patients presented a clinical response and underwent re-laparoscopy. Negative peritoneal metastasis and peritoneal cytology were confirmed in 25 patients who proceeded to undergo the conversion surgery. Compared with palliative therapy group, surgery group had a significantly better median progression-free survival (PFS) (20.3 vs 5.1 months; p < 0.001) and a prolonged median overall survival (OS) (33.4 vs 11.7 months; p < 0.001). In the surgery group, 24 (96%) of 25 patients were performed laparoscopic gastrectomy radical laparoscopic gastrectomy with more than D2 lymph node dissection (only one patient underwent open gastrectomy), 19 (76%) patients achieved R0 resection, 2 (8%) patients achieved pathologic complete response (pCR) and 4 (16%) patients reached tumor regression grade (TRG) 0-1. It was observed that patients with PCI score ≤ 2 experienced a longer median OS in comparison to those with PCI scores > 2 ( unreached vs 28.5 months, P < 0.031). And multivariate analysis associated with PFS among surgery cases identified signet ring cell carcinoma as an independent adverse prognostic factor (HR 4.66; 95% CI 1.19–18.22; p = 0.027). No serious treatment-related adverse events resulted in termination of treatment or death. Conclusions: Conversion surgery following first-line anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy represented a promising treatment strategy for GC patients with peritoneal metastasis. When immunochemotherapy is effective, active second-look staging laparoscopy should be performed to clarify the possibility of conversion surgery.