Outcome of Patients Treated Within and Outside a Randomized Clinical Trial on Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: Extrapolation of a Randomized Clinical Trial (CROSS)

Abstract

Background: Randomized clinical trials (RCTs) can provide a high level of evidence for medical decision making, but it is unclear if the results apply to patients treated outside such trials.

Objective: The aim of this study was to retrospectively compare outcomes of patients with esophageal cancer treated within and outside an RCT.

Methods: All patients receiving neoadjuvant chemoradiotherapy (nCRT) plus surgery for esophageal cancer between 2002 and 2008 (ChemoRadiotherapy for Esophageal cancer followed by Surgery Study [CROSS] cohort) who participated in multicenter, phase II-III trials were compared with patients who underwent the same treatment outside the trial between 2008 and 2013 (post-CROSS cohort). The differences between these cohorts were analyzed using t tests, while logistic regression models were used to evaluate adverse events. Overall and disease-free survival were calculated using the Kaplan-Meier method and Cox regression analyses.

Results: A total of 208 CROSS patients and 173 post-CROSS patients were included in this study. Patients from the post-CROSS cohort were older, had more co morbidities, and had poorer performance status. Clinical N stage, but not cT stage, was worse in the post-CROSS cohort. There were no statistically significant differences in adverse events (pulmonary, cardiac, or anastomotic complications) or survival between the comparison cohorts.

Conclusion: The outcomes of patients treated with nCRT plus esophagectomy for cancer have a high external consistency and can be extrapolated to the daily practice of physicians involved in the treatment and care of esophageal cancer patients.

Fig. 1

Overall survival of 381 patients, divided into the CROSS (n = 208) and post-CROSS (n = 173) cohorts for patients with oesophageal or junctional cancer who underwent chemoradiotherapy according to CROSS followed by surgery (p = 0.90). cum survival percentages of cumulative overall survival, where 1.0 means 100% of the cohort, decreasing over time, 5-year OS 5-year overall survival, expressed in months, CROSS ChemoRadiotherapy for Esophageal cancer followed by Surgery Study, mo months

Fig. 2

Disease-free survival of 381 patients, divided into the CROSS (n = 208) and post-CROSS (n = 173) cohorts for patients with oesophageal or junctional cancer who underwent chemoradiotherapy according to CROSS followed by surgery (p = 0.69). cum survival percentages of cumulative disease-free survival, where 1.0 means 100% of the cohort, decreasing over time, 5-year DFS 5-year disease-free survival, expressed in months, CROSS ChemoRadiotherapy for Esophageal cancer followed by Surgery Study, mo months