M. Wanyan2, B. Nuckles1, K. Frank1, K. A. Young1, R. L. Hoffman1, J. A. Blansfield1 1Geisinger Surgery Institute, Danville, PA, USA 2Geisinger Commonwealth School of Medicine, Scranton, PA, USA
Introduction:
Esophageal cancer is an aggressive cancer with 5-year survival rates of 20%. Due to its aggressive nature, most therapeutic approaches are multimodal, involving chemotherapy, radiation, and surgery. The landmark CROSS trial demonstrated a survival benefit of neoadjuvant chemoradiation versus surgery alone in T1N1 or T2-3N0-1 patients. Theoretically, the benefits of chemotherapy and radiation should be most pronounced in patients with advanced disease and least pronounced in early-stage disease. Thus, T2N0M0 cancer, the nebulous intermediary, remains a difficult stage to treat; national guidelines offer multiple treatment options. This study aims to compare survival outcomes in clinical T2N0M0 esophageal cancer via treatment modality, identify factors associated with treatment modality, and compare clinical to pathologic stage.
Methods:
A retrospective study was performed of clinical T2N0M0 esophageal cancer using the National Cancer Database (NCDB 2006-2016). Patients who underwent neoadjuvant chemoradiation followed by surgery (NCRT+ESOPH) were compared to patients who underwent esophagectomy first (ESOPH). A subgroup of patients who underwent chemotherapy and/or radiation following esophagectomy was used for overall survival comparison using Kaplan-Meier estimate and log-rank tests for the entire study duration and at 1, 3, and 5 years. Multivariable logistic regression was used to determine factors associated with order of treatment.
Results:
There were 1662 patients in this study (NCRT+ESOPH: 904 [54.4%], ESOPH: 758 [45.6%]). In the ESOPH arm, 159 (9.6%) patients had chemotherapy and/or radiation following surgery (ESOPH+Adjuvant). Among patients who received chemotherapy and/or radiation, survival benefit was improved but not statistically significant when chemoradiation was performed preoperatively (NCRT+ESOPH median survival was 64.8 months versus 50.1 months for ESOPH+Adjuvant, p = 0.537). Use of NCRT+ESOPH was correlated with more recent year of diagnosis (median year of diagnosis was 2013 versus 2011 for ESOPH, p < 0.001). Between 2006 to 2016, NCRT+ESOPH treatment rates rose from 33% to 74%. Patients who received NCRT+ESOPH were younger and more likely to have reported no comorbidities (Charlson-Deyo score of 0: 71.8% versus 61.2%, p < 0.001). Notably, 41% percent of patients were over-staged (T1 or lower after esophagectomy first – ESOPH group), and at least 32.5% were under-staged (N ≥ 1 in ESOPH group).
Conclusion:
T2N0M0 remains a difficult tumor to characterize, and pathological staging corresponds poorly to clinical staging. The use of neoadjuvant therapy has risen significantly in the past decade. However, the lack of a significant survival benefit to neoadjuvant therapy that we find may be secondary to over- or under-staging. Future work is needed to more accurately stage these patients so those who should undergo chemotherapy and radiation get the treatment they need and those who do not are spared.