In a Dutch noninferiority phase III trial (SANO) reported in The Lancet Oncology, van der Wilk et al found that active surveillance was noninferior to standard surgery in terms of 2-year overall survival among patients with esophageal cancer who had a clinical complete response after neoadjuvant chemoradiotherapy.
Study Details
In this trial, 12 Dutch hospitals, which enrolled 1,309 eligible patients between November 2017 and January 2021, randomly assigned patients to receive active surveillance (n = 198) or standard esophagectomy (n = 111) after a clinical complete response to chemoradiotherapy.
Neoadjuvant chemoradiotherapy consisted of five weekly cycles of paclitaxel at 50 mg/m2 and carboplatin AUC = 2; a total of 41.4 Gy of external-beam radiotherapy was given in 23 fractions of 1.8 Gy for 5 days per week, starting on the day of the first course of chemotherapy. The primary endpoint of the trial was overall survival in the modified intent-to-treat analysis (allowing patients to cross over to surgery at clinical complete response) and in the intent-to-treat population.
Key Findings
Median follow-up was 38 months (interquartile range = 32–48 months). The overall survival rate at 2 years was 74% (95% confidence interval] CI = 69%–78%) in the active surveillance group vs 71% (95% CI = 62%–78%) in the surgery group in the modified intent-to-treat analysis, with noninferiority being met (hazard ratio = 1.14, 95% CI = 0.74–1.78). In the intent-to-treat analysis, the 2-year overall survival rate was 75% (95% CI = 68%–80%) vs 70% (95% CI = 63%–77%, with inferiority again being shown; the hazard ratio was 0.83 (95% CI = 0.53–1.31).
The investigators stated: “The frequency of postoperative complications of any grade and postoperative mortality after standard surgery or postponed surgery after active surveillance was similar between groups.”
They concluded: “Overall survival after active surveillance for esophageal cancer was noninferior compared with standard surgery after 2 years. For the long-term efficacy of active surveillance, extended follow-up is required. The results of the present trial could be used for patient counseling and shared decision-making.”
Berend J. van der Wilk, MD, PhD, of the Department of Surgery, Erasmus M.C. Cancer Institute, University Medical Centre, Rotterdam, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the Dutch Cancer Society and the Netherlands Organisation for Health Research and Development. For full disclosures of the study authors, visit thelancet.com.
