Abstract
Simple SummaryAround 20% of gastric cancer patients develop peritoneal metastasis after preoperative chemotherapy and curative surgery. Patients with peritoneal metastasis as a single site of metastasis may potentially benefit from prophylactic strategies. In this post-hoc analysis of the international phase III CRITICS trial, we aim to identify factors that can distinguish patients at high risk for developing peritoneal metastasis as a single site. Diffuse or mixed histological subtype, tumors with serosal involvement (ypT4) and advanced lymph node stage (ypN3 or a tumor positive lymph node ratio >20%) were independent risk factors for isolated peritoneal metastasis after preoperative chemotherapy and curative surgery. The combination of these risk factors identifies a subgroup that may benefit from treatment strategies that aim to prevent peritoneal metastasis.Gastric cancer (GC) patients at high risk of developing peritoneal metastasis (PM) as a single site of metastasis after curative treatment may be candidates for adjuvant prophylactic strategies. Here we investigated risk factors for metachronous isolated PM in patients who were treated in the CRITICS trial (NCT00407186). Univariable and multivariable analyses on both metachronous isolated PM and ‘other events’, i.e., (concurrent) distant metastasis, locoregional recurrence or death, were performed using a competing risk model and summarized by cumulative incidences. Isolated PM occurred in 64 of the 606 (11%) included patients. Diffuse or mixed histological subtype, ypT4 tumor stage and LNhigh (ypN3 lymph node stage or a lymph node ratio >20%) were independent risk factors for isolated PM in both univariable and multivariable analyses. Likewise, LNhigh was an independent risk factor for ‘other events’. Patients with tumors who were positive for all three independent risk factors had the highest two-year cumulative incidence of 43% for isolated PM development. In conclusion, diffuse or mixed histological subtype, ypT4 and LNhigh were identified as independent risk factors for isolated PM in patients treated with preoperative chemotherapy followed by surgical resection. The combination of these factors may identify a subgroup that may benefit from PM-preventing treatment strategies.
Highlights
IntroductionGastric cancer is the third most common cause of cancer-related deaths worldwide [1]
Gastric cancer is the third most common cause of cancer-related deaths worldwide [1].Survival after potentially curative surgery remains low, frequently due to tumor recurrence in the peritoneal cavity
After the exclusion of patients with neuroendocrine carcinomas (n = 5; 1%), or peritoneal metastasis detected during histopathological examination of the resection specimen (n = 14; 2%) and post-operative deaths (n = 11; 2%), 606 patients were included in this analysis (Figure 1)
Summary
Gastric cancer is the third most common cause of cancer-related deaths worldwide [1]. Survival after potentially curative surgery remains low, frequently due to tumor recurrence in the peritoneal cavity. Several multimodality treatment regimens have been introduced over the last decades to improve survival and reduce gastric cancer recurrence rates. Perioperative chemotherapy is currently the standard of care throughout many parts of Europe and the United States, and has improved the five-year overall survival rates for resectable gastric cancer by up to 45% [2,3]. Despite the administration of preoperative chemotherapy, peritoneal metastasis incidences have not decreased over the last decades [4].
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