Outcomes of stage II-IVA esophageal and esophagogastric cancers treated with multimodal therapy: A 13-year single-center study.

e16126 Background: The treatment landscape for locoregional esophageal (Eso) and gastroesophageal junction (GEJ) cancers (Ca) has evolved significantly over the past decade. This study aims to compare survival outcomes of these patients (Pts) treated with different front-line modalities in a real-world setting. Methods: In this retrospective study, we included adult Pts diagnosed with stages II-IVA squamous (SC) or adenocarcinoma (AC) Eso and GEJ Ca treated at Cleveland Clinic from 1/2010-12/2022. We excluded Pts who had Ca in cervical Eso, T4b disease, gastric Siewert classification 3 and Pts who did not receive systemic therapy. Data included demographics, comorbidities, ECOG, BMI, tumor stage, and treatment modalities. Responses were assessed using RECIST 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were calculated from diagnosis. Multivariable Cox proportional hazards (CPH) models were used to adjust for confounding. Results: Key baseline variables are summarized in Table 1 In the AC subtype, the median follow up was 64 months and 2-year OS was 58% (95%CI: 54-62). The three most common therapeutic modalities were definitive chemoradiation (CRT) (280, 49%), preoperative CRT followed by esophagectomy (162, 29%) and pre/perioperative chemotherapy (CTX) followed by esophagectomy (56, 9.9%). Response rate was 79%. In a multivariable CPH model, when compared to Pts who had definitive CRT, preoperative CRT + esophagectomy and pre/perioperative CTX + esophagectomy were associated with improved OS (HR 0.72, 95%CI 0.55-0.95, P = 0.02) (HR 0.47, 95%CI 0.30-0.73, P < 0.001), respectively. Stages III & IV vs. II and increasing age had worse survival but increasing BMI had better survival (all P < 0.05). In the SC subtype, the median follow up was 55 months and 2-year OS was 51% (95%CI: 42-62). The two most common therapeutic modalities were definitive CRT (70, 73%) and preoperative CRT followed by esophagectomy (19, 20%). Response rate was 70%. In a multivariable CPH model, Pts who received preoperative CRT + esophagectomy had similar OS and PFS to Pts who had definitive CRT (HR 0.98, 95% CI 0.53-1.82, P > 0.9) (HR 0.81, 95% CI 0.44-1.50, P = 0.5). Stage IVA had worse PFS than stage II (P < 0.05). Conclusions: In Stage II-IVA Eso and GEJ AC, preoperative CRT or pre/perioperative CTX followed by esophagectomy significantly improved survival compared to definitive CRT. Additionally, the observed association of higher BMI with improved survival in AC. In SC, both definitive CRT and preoperative CRT followed by esophagectomy resulted in similar long-term survival outcomes. These findings highlight the importance of histology-directed and patient-specific treatment strategies. Key baseline variables. Squamous CaN = 105 AdenocarcinomaN = 566 Median Age (years) 64 (58, 72) 65 (58, 71) Male 63% 86% White 77% 96% Never smoker 21% 25% Stage II 36% 24% Stage III 59% 66% Stage IVA 5% 10% Surgery 37% 70% Radiation 93% 89%