Ten-year overall survival of localized lower thoracic and esophagogastric junction carcinoma receiving trimodality therapy: A National Cancer Database analysis.
Authors: Kakish Hanna , Naleid Nikolas , Towe Christopher W. , Hoehn Richard , Mears Veronica , Selfridge J. Eva , Lumish Melissa Amy , Conces Madison , Bajor David L , MOHAMED AMR , Henke Lauren E. , Dorth Jennifer Anne , Mahipal Amit , Chakrabarti Sakti 
Published: January 2024

278 Background: Trimodality therapy, consisting of chemotherapy and radiation followed by esophagectomy, represents the prevailing standard of care for most patients with localized lower thoracic and esophagogastric junction (EGJ) carcinoma. However, robust data reporting the survival of this patient group treated in the real-world setting is lacking. The primary objective of the current study was to comprehensively analyze the long-term survival of this patient population receiving treatment in a real-world setting and the variables that significantly influence the survival. Methods: We identified adult patients in the National Cancer Database with localized (cT1N+M0 or cT2-T4N+/-M0) lower thoracic or EGJ adenocarcinoma (AC) or squamous cell carcinoma (SCC) receiving trimodality therapy between 2004 and 2020 with multi-agent chemotherapy and ≥ 4139 cGy of radiation followed by esophagectomy. The primary endpoint of the analysis was overall survival (OS), estimated using the Kaplan-Meier method. The impact of clinical and demographic features on OS was determined using the log-rank test. We performed a multivariable (MV) Cox analysis to evaluate the independent association of clinical and demographic variables on OS (data presented as hazard ratio [HR] and 95% Confidence Interval [CI]). Results: The analysis included 21,965 patients, characterized by a median age of 63 years, predominance of males (85.9%), non-Hispanic white patients (89.4%), and AC histology (93.6%). Most patients had T2/T3 tumors (87.3%) and regional lymph node (LN) involvement (62.1%). The 10-year OS for the entire cohort was 27.6% (95% CI, 26.8%-28.5%), with a median OS of 40.7 months (95% CI, 39.7-41.6). For patients aged ≤ 65, the 10-year OS was 31.2% (95% CI, 30.2%-32.3%), with a median OS of 44.1 months (95% CI, 42.8-45.5). On MV analysis, the following factors were associated with inferior OS with CI in the parenthesis: age ≥ 66 years (1.17, 1.11-1.22); male gender (1.13, 1.08-1.19); histology, AC vs. SCC (1.19, 1.10-1.28); T4 vs. T1-T3 tumor stage (1.20, 1.07-1.34); lymph node involvement (1.22, 1.18-1.27); Charlson-Deyo score ≥ 2 (1.23, 1.15-1.32); uninsured vs private insurance (1.20, 1.05-1.36); and low-volume facility (1.08, 1.01-1.16). Furthermore, patients treated after 2012 (2013-2019) had modestly improved OS (0.87, 0.84-0.90), perhaps reflecting the impact of the CROSS trial result published in 2012. Conclusions: This study illustrates the grim long-term survival of patients with localized lower thoracic and EGJ cancer undergoing standard trimodality therapy, underscoring the urgent necessity for innovative therapeutic approaches for this patient group. The improvement in OS following the publication of the CROSS trial was modest.