Incidence, risk factors and tumor spectrum of second primary cancers after gastric cancer: a multicenter cohort study with long-term follow-up.

backgroundThe development of second primary cancers (SPCs) has become an important late effect in gastric cancer (GC) survivors, yet its incidence, risk factors, and clinical implications remain poorly defined. This study aimed to evaluate the long-term risk of SPCs, identify clinical factors associated with SPC occurrence, and describe detection patterns and stage distribution of SPCs during long-term follow-up.

methodsPatients with GC who underwent curative-intent radical gastrectomy between 2007 and 2021 were identified from the Multidisciplinary Alliance of Gastric Integrative Studies (MAGIS) cohort. Clinical factors associated with SPC occurrence were selected using LASSO-penalized Cox regression, and exploratory risk-based stratification was performed. Stage distribution was descriptively compared between SPCs detected during asymptomatic surveillance and those diagnosed after symptom onset.

resultsAmong 11,027 GC survivors (8,519 men and 2,508 women), 241 (2.19%) developed SPCs during a follow-up of up to 16 years. The cumulative incidence of SPCs was 1.25% (95% CI, 1.03%-1.46%) at 5 years, 2.97% (95% CI, 2.55%-3.39%) at 10 years, and 4.15% (95% CI, 3.40%-4.91%) at 15 years after gastrectomy. The most frequent SPCs were lung (23.2%), colorectal (21.6%), and esophageal (12.9%) cancers, showing marked sex-specific differences: lung cancer predominated in males, whereas cervical cancer was most common in females. Factors associated with SPC occurrence included older age at time of gastrectomy (HR 1.04, 95% CI 1.02-1.05; p < 0.001), chronic HBV/HCV infection (HR 2.15, 95% CI 1.29-3.58; p = 0.003), family history of cancer (HR 1.57, 95% CI 1.16-2.12; p = 0.003), and elevated preoperative systemic inflammation (Log-SIRI; HR 1.86, 95% CI 1.31-2.65; p < 0.001). The derived model stratified patients into low-, intermediate-, and high-risk groups with corresponding 10-year SPC risks of 2.07%, 3.61%, and 4.33%. SPCs detected during asymptomatic surveillance were more frequently diagnosed at stage I than those identified after symptom onset (47.4% vs 17.6%; p < 0.001).

conclusionsSPCs represent an important long-term health burden among GC survivors, with distinct sex-specific disease patterns. The exploratory risk-scoring model showed preliminary risk stratification, and SPCs detected during asymptomatic surveillance were more often diagnosed at an earlier stage. These findings support further evaluation of risk-adapted, organ- and sex-specific surveillance strategies in methodologically rigorous studies.