Abstract
BACKGROUND: Stomach cancer remains the fifth leading cause of cancer death, with racial/ethnic and geographic differences. As survival improves, these survivors face elevated risks of second primary cancers (SPCs). We evaluated SPC risk and post-SPC survival by race/ethnicity and between the U.S. and South Korea. METHODS: We analyzed patients with stage I-III stomach cancer (2012-2020) from the U.S. SEER-17 and Korea Cancer Public-Library Database. SPCs were defined as non-gastric cancers diagnosed > 1 year post initial diagnosis. Cumulative SPC incidence was estimated using Aalen-Johansen method to account for competing death. Cox regression assessed survival impact of SPC development. RESULTS: Among 19,595 U.S. and 204,240 Korean patients, 1,050 and 6,908 developed SPCs, respectively. In the U.S., 5-year SPC incidence was highest in Black (7.4% [6.1-8.6]) and lowest in Pacific Islanders (4.5% [2.3-6.7]). Notable heterogeneity in SPC incidence was observed across Asian subgroups, with Korean Americans showing the highest (6.9% [4.7-9.1]) and Filipinos the lowest (4.4% [1.9-7.2]). In contrast, Korean survivors in South Korea had the lowest SPC incidence (3.8% [3.7-3.9]). SPC development was associated with higher mortality (HR = 2.22 [1.96-2.52]), with a stronger effect in Asians (HR = 3.12) than Whites (HR = 1.96; interaction P < 0.1). Among Asian subgroups, SPC development was associated with the highest mortality in Vietnamese (HR = 13.6) and the lowest in Filipino survivors (HR = 1.54; interaction P < 0.01). Among Korean survivors in South Korea, SPC development conferred a modest increase in mortality risk (HR = 1.68 [1.61-1.75]). CONCLUSIONS: SPC risk and outcomes in stomach cancer survivors vary by race/ethnicity and country, particularly within Asian subgroups.