Concurrent Chemoradiation is Associated With Improved Overall Survival Over Radiation Alone in the Treatment of Non-operative Clinical T1N0M0 Esophageal Cancer

Abstract

For non-operative patients with clinical T1N0M0 esophageal cancer, the outcomes of concurrent chemoradiation (CRT) versus radiation therapy (RT) alone are currently not well characterized. Our goal was to compare overall survival (OS) between these two treatment modalities, and evaluate if RT alone may demonstrate similar outcomes to concurrent CRT at this early stage. The National Cancer Database (NCDB) was used to identify cT1N0M0 esophageal cancer patients. Concurrent CRT was defined as starting chemotherapy and radiation therapy within a 14-day period. Multivariate logistic regression was done to identify factors independently associated with receiving RT alone. One-to-one propensity matching (PM) on patient and tumor characteristics was performed to overcome selection bias in the allocation of these two treatment types. Kaplan-Meier analysis was used to compare overall survival among the propensity matched groups. From 1998 to 2012, 4,837 cT1N0M0 esophageal cancer patients were identified. Of all cT1N0M0 patients, 945 received CRT while 333 received RT alone. The majority (1,225 or 95.9%) of these patients were categorized as cT1, and not sub-classified as T1a or T1b. Median age in the RT only group was significantly older than the CRT patients (80 years, IQR 73 – 85 years versus 70 years, IQR 62 – 78 years, p<0.001). There was no difference in the median RT dose between the two groups (CRT 50Gy, IQR 43.2 – 50.4Gy versus RT alone 47Gy, IQR 37.5 – 59.4 Gy, p=0.3). On multivariate analysis, increasing age (per year OR 1.09, 95% CI 1.07 – 1.11, p<0.001), female gender (OR 1.52, 95% CI 1.06 – 2.19, p=0.02), and a Charlson-Deyo cormorbidity score of ≥2 (reference score 0: OR 2.69, 95% CI 1.44 – 5.01, p=0.002) were independently associated with receiving RT alone. Of the 147 RT only patients with complete data, 133 (90%) were propensity matched to 133 CRT patients. In the overall propensity matched analysis, CRT patients had significantly improved OS compared to RT alone patients (19.9 months versus 11.5 months, p<0.001). With separate propensity matches by histologic subtype, the survival benefit for CRT persisted for both squamous cell carcinoma (26.5 months versus 10.8 months, p<0.001) and adenocarcinoma (16.8 months versus 14.3 months, p=0.048). By comparison, of the 1,683 cT1N0M0 patients that received an esophagectomy, median OS was 44.8 months. For non-operative cT1N0M0 esophageal cancer, RT alone does not appear to confer the same survival advantage as concurrent CRT, even after adjusting for patient and tumor characteristics. Patients that are not surgical candidates but are fit for concurrent therapy should be considered for definitive chemoradiation.