Abstract
Esophageal cancer (EC) is the 8th most common cancer worldwide, with striking differences in incidence in different regions of the world. Incidence rates range from 1 per 100,000 in Western Africa to 20 per 100,000 in Eastern Asia, with intermediate rates reported in Europe (about 10 per 100,000) (1). EC is also a devastating malignancy, which ranks 6th on the list of cancer-mortality causes (1). Surgery is the mainstay of treatment for patients with localized or locally advanced EC (2), although some patients may be cured with chemoradiation (CRT) only [definitive CRT (dCRT)] (3,4). Over the past 2 decades, the management of resectable EC has dramatically changed with the advent of neoadjuvant chemotherapy (CT) and neoadjuvant CRT (NCRT). NCRT provides a 23% reduction of the risk of death, as reported in a meta-analysis by Sjoquist et al. (5). The benefit of NCRT over surgery alone has been also strengthened by the results of the so-called CROSS trial, which demonstrated a dramatic 35% reduction in the risk of death with the use of NCRT (6). Of note, dCRT appears to be at least equivalent to surgery in terms of survival in patients with squamous cell carcinoma EC who are fit for surgery and are responsive to induction CRT, as reported in a recent Cochrane review (7). For patients who do not undergo surgery for some reason (patients not suitable for surgery due to the local extent of disease or as a result of comorbidities), dCRT has represented a standard of care (8,9) since the pioneering RTOG 85-01 trial was reported in 1992 (10). A significant survival benefit was reported favoring dCRT over radiation therapy (RT) only for patients with localized EC. Together with concurrent RT (50 Gy, 25 fractions), patients received 2 cycles of fluorouracil and cisplatin, which were given at 4-week intervals. Two additional cycles are given 3 weeks apart after the end of dCRT. Briefly, this regimen provides an actual 26% 5-year survival rate versus 0% with RT only (11). Up to now, RT dose escalation (11), paclitaxel-based regimens with induction CT preceding CRT (12), addition of cetuximab to standard dCRT (13,14), and the substitution of cisplatin by oxaliplatin (4) have not produced a significant survival benefit over the RTOG 85-01 regimen.