Results of the FFCD 9901 trial in early-stage esophageal carcinoma: is it really about neoadjuvant therapy?

therapy does not improve survival and increases postoperative mortality in patients with early-stage disease. 13 However, patterns of failure analysis showed a significant improvement in local control in patients who were assigned to receive neoadjuvant therapy, nearly halving the rate of locoregional recurrence (29% v 15%). Disease recurrence rates were also significantly reduced in patients receiving neoadjuvanttreatment.TheselocalfailureratesmirrortheDutchtrial ratesoflocoregionalrecurrencereductionfrom34%(surgeryonly)to 14%(neoadjuvanttherapyandsurgery)inamoreadvancedgroupof patients.Thesedatahighlightthechallengeofsurgeryinextirpatingall locoregional disease even in patients with early-stage disease. How does one reconcile the differences in survival outcomes betweentheFrenchandDutchstudies?Thereareseveralpossibilities. First, small patient numbers in the FFCD 9901 trial reduce the statistical power of detecting a survival benefit, such as that seen in the Dutch study, despite similar reduction in disease recurrence rates in patients receiving neoadjuvant treatment. Next, the histologic subtypesweredifferentinthesetwostudies.Seventypercentofpatientsin the French study had a histologic diagnosis of squamous cell carcinoma compared with 23% in the Dutch study. Squamous cell carcinoma is a malignancy often arising in patients with longstanding histories of alcohol and tobacco use and associated comorbidities, whereas esophageal adenocarcinoma is associated with obesity, gastroesophageal reflux disease, and Barrett’s disease. The underlying biology and natural history of these two malignancies is different. Finally, the French study included more patients with early-stage disease(fewernode-positiveandT3patients)withcorrespondinghigh