Survival outcomes for de novo versus relapsed stage IV gastric and gastroesophageal junction (GEJ) adenocarcinoma.
148 Background: In gastric/GEJ cancer, 40% of patients (pts) are metastatic at diagnosis ( de novo stage IV) and up to 70% with locoregional disease recur (relapsed stage IV). We compared survival outcomes between de novo vs relapsed stage IV. Methods: A retrospective observational study of stage IV gastric/GEJ pts was conducted (2012-2015). Overall survival (OS) was from date of stage IV diagnosis. PFS1 defined the period from stage IV diagnosis to first progression. PFS2 was from first to second progression. For relapsed stage IV pts, disease-free interval (DFI) was the period from initial diagnosis to metastatic relapse. Cox proportional hazards models compared OS, PFS1 and PFS2 between de novo vs relapsed stage IV pts, stratified by DFI [ < 6, 6-12 and > 12 months (mo)] and controlled for baseline patient characteristics. Results: Of 198 pts, 62% were male and median age was 64 years (26-93), with 64% gastric and 36% GEJ adenocarcinomas. Primary therapy for locoregional pts included surgery (75%), perioperative chemotherapy (42%) and radiotherapy (42%). De novo and relapsed stage IV pts represented 68% and 32% of the cohort respectively. Median follow-up was 13 mo. Controlled for age, performance status and Charlson comorbidity index, there were no significant differences in OS (median OS 12.5 ( de novo) vs 12.2 mo (relapsed); HR 1.22, 95% CI 0.83-1.77, p = 0.31), PFS1 (6.8 vs 7.4 mo; HR 1.00, 95% CI 0.65-1.56, p = 0.98) or PFS2 (3.8 vs 3.0 mo; HR 1.03, 95% CI 0.44-2.41, p = 0.95). Median OS for relapsed stage IV patients were different by DFI groups (log-rank p = 0.02): 22.9 mo (for DFI > 12mo; n = 31), 11.2 mo (DFI 6-12; n = 19) and 7.5 mo (DFI < 6; n = 14). Additionally, OS was significantly better if the DFI was greater than 12 mo, compared with de novo stage IV (HR 0.50, 95% CI 0.28-0.88, p = 0.02). Conclusions: There was no observed difference in the natural history of de novo vs relapsed stage IV gastric/GEJ pts. DFI was strongly prognostic with median OS (from date of relapse) approaching 2 years for relapsed pts with DFI > 12 mo. In addition to implications for treatment strategy, tumor biology within subgroups should be examined to identify novel biomarkers and potential therapeutic targets.