Clinicopathologic features, actionable biomarkers, and treatment patterns in early-onset gastric cancer: A real-world Latin American cohort.

Abstract

e23385 Background: Early-onset gastric cancer (EOGC), defined as diagnosis before age 50, is biologically aggressive and often diagnosed at advanced stages. However, real-world data from Latin America remain limited. We aimed to characterize clinicopathologic features, actionable biomarkers, treatment patterns, and survival in an EOGC cohort. Methods: We conducted a retrospective cohort study of EOGC at a high-complexity Latin American center over a 10-year period (2014–2023). Histology followed WHO and Lauren criteria. Biomarkers included HER2, PD-L1 CPS and MSI when available. Stage-specific treatment patterns were described, and overall survival (OS) was estimated using the Kaplan–Meier. Results: A total of 54 patients were included (median age at diagnosis: 41 years (IQR 35–46), and 68.5% were female). At diagnosis, 31.5% had stage I-II disease, 11.1% stage III, and 57.4% stage IV. Staging laparoscopy was performed in 57.4%, revealing neoplastic involvement in 42.6%. Aggressive pathology predominated, with poorly cohesive carcinoma/signet ring features in 68.5% and diffuse-type histology in 70.0%. Actionable molecular alterations were identified PD-L1 CPS ≥1 in 20.4%, HER2 positivity in 9.4% and MSI-high status in 5.7% of patients. Biomarker overlap was rare, with only one HER2/PD-L1–positive tumor and one PD-L1/MSI-high tumor. Among early-stage patients (stage II), 88.2% received perioperative and/or adjuvant systemic therapy, predominantly platinum-based regimens (86.7%), most commonly FLOT (40.0%). Curative-intent gastrectomy was performed in 76.5%, mainly total gastrectomy, and most operated patients received adjuvant therapy. Among stage III patients (n = 6), 83.3% received perioperative systemic therapy, all with platinum-based chemotherapy, most frequently FLOT (33.3%). Curative-intent gastrectomy was performed in 83.3%. Among stage IV patinetes n = 31, systemic therapy predominated. First-line treatment consisted mainly of platinum-based chemotherapy (87.1%), most commonly FOLFOX (54.8%), with trastuzumab added in HER2-positive tumors. Palliative surgery such as HIPEC was performed in 29.0%. Maintenance therapy was administered in 35.5%, primarily fluoropyrimidine-based, with immunotherapy or trastuzumab in selected patients. After progression, 48.4% received second-line therapy, mainly fluoropyrimidine- or taxane-based regimens. At 24 months, overall survival differed by clinical stage (log-rank p = 0.011), with OS rates of 100% stage I, 70% stage II, 50% stage III, and 40% stage IV. Conclusions: In this real-world Latin American cohort, early-onset gastric cancer showed aggressive features and molecular heterogeneity, underscoring the need for comprehensive biomarker profiling to enable targeted and immunotherapy-based strategies with potential survival benefit in young patients.