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Background: The development of esophageal or gastroesophageal junction adenocarcinoma (EAC/GEJAC) in patients less than 40 years of age is thought to be associated with a more aggressive tumor biology and a worse outcome compared to patients over 40 years. Our objective was to determine the impact of younger age on survival of EAC/GEJAC utilizing a nationwide patient registry.
Methods: Using the Surveillance Epidemiology and End Results (SEER) database, we identified all patients diagnosed with EAC/GEJAC during the years 2000-2009. Patients were stratified by age: <40 years, 40-60 years, or >60 years. Patients <40 years were then compared to those >60 years, and survival outcomes were assessed by the Kaplan-Meier method and Cox-regression.
Results: Of 15, 816 patients with EAC/GEJAC diagnosed during the study period, 67.3% (n=10,641) were >60 years, and 1.7% (n=269) were <40 years old. The incidence rates in both cohorts did not change over the study period. When compared to the older cohort, patients <40 years were more likely to be male (p<0.0001), present with AJCC stage III/IV disease, p<0.0001), and receive both radiation and surgery for curative intent (29 vs. 13.6%, p<0.001). Patients <40 years had significantly better median overall survival (OS) and median disease-specific survival (DSS): 15 vs. 10 months and 14 vs. 12 months, respectively; p<0.0001. Stratifying by AJCC stage, younger patients had superior DSS regardless of stage: stage I: Not reached (NR) vs. 55 months, p<0.0001; stage II: NR vs. 25 months, p<0.001, stage III: 19 vs. 15 months, p<0.0001; stage IV: 10 vs. 6 months, p<0.0001. When stratifying by therapy delivered, younger patients had superior DSS in the surgery only cohort (NR vs. 59 months, p=0.003) and similar survival in the surgery + radiation and radiation alone cohorts. Cox regression confirmed age <40 is an independent predictor of both improved OS (p<0.0001) and improved DSS (p=0.0007).
Conclusions: Based on analysis of the SEER registry, while EAC/GEJAC remains a rare entity in patients <40 years of age, these patients can be expected to have superior outcomes as compared to older cohorts, especially with early diagnosis. An aggressive approach to both early diagnosis and treatment of this disease should continue regardless of age.
5-year overall and disease-specific survival for EAC/GEJAC by age and AJCC stage

AJCC stage	All stages		Stage l		Stage II		Stage III		Stage IV
	Median (months)	5 -year survival	Median (months)	5-year survival	Median (months)	5-year survival	Median (months)	5-year survival			p value
Overall Survival
<40 years	15	0.22	NR	0.83	NR	0.54	16	0.06	8	0.06
>60 years	10	0.15	31	0.36	21	0.24	14	0.12	6	0.02	<0.0001
Disease-specific Survival
<40 years	14	0.24	NR	0.65	NR	0.52	19	0.00	10	0.05
>60 years	12	0.20	57	0.48	25	0.30	15	0.15	6	0.02	<0.0001

NR=Not reached