SANO
Neoadjuvant chemoradiotherapy followed by active surveillance versus standard surgery for oesophageal cancer (SANO trial): a multicentre, stepped-wedge, cluster-randomised, non-inferiority, phase 3 trial
Phase 3N = 309
- Population
- Locally advanced oesophageal carcinoma with a clinical complete response after neoadjuvant chemoradiotherapy, age 18 or older, treated with curative intent; no restrictions on comorbidity or performance status
- Design
- Multicentre, stepped-wedge, cluster-randomised, non-inferiority phase 3 trial in 12 Dutch hospitals. After an initial phase in which all hospitals performed standard surgery, hospitals were randomised (computer-generated sequences) to move to active surveillance. Patients with a clinical complete response after neoadjuvant chemoradiotherapy (no tumour on endoscopic biopsies, ultrasound and PET-CT) had active surveillance or standard surgery (oesophagectomy within 2 weeks of reaching clinical complete response). 1115 screened and 309 included between November 2017 and January 2021. Primary endpoint overall survival, modified intention-to-treat (crossover allowed at the time of clinical complete response) and intention-to-treat. Non-inferiority: 2-year survival for active surveillance no more than 15% below standard surgery. Netherlands Trial Register NTR-6803 (not an NCT number).
- Primary endpoint
- OS
- Arms
- Active surveillance (experimental, n = 198): Active surveillance after clinical complete response to neoadjuvant chemoradiotherapy
- Standard surgery (control, n = 111): Oesophagectomy within 2 weeks after reaching clinical complete response
- People
- van der Wilk BJ
OSHR 1.14 (95% CI 0.74–1.78)Δ 24-month OS+3 pointsOSHR 0.83 (95% CI 0.53–1.31)Δ 24-month OS+5 points
Show the numbers
| Endpoint | Analysis | Active surveillance | Standard surgery | Effect |
|---|---|---|---|---|
| OSModified intention-to-treat (crossover allowed at the time of clinical complete response) | primarymedian follow-up 38 monthsvan 2025 | 74% at 2 y (69–78%) | 71% at 2 y (62–78%) | HR 1.14 (95% CI 0.74–1.78)Non-inferiority was met: the one-sided 95% boundary was 7% lower (margin 15%). The abstract gives no P value for the survival comparison and states no significant difference in overall survival. The abstract does not state which arm is the numerator of the hazard ratios (1.14 modified intention-to-treat, 0.83 intention-to-treat). |
| OSIntention-to-treat | primarymedian follow-up 38 monthsvan 2025 | 75% at 2 y (68–80%) | 70% at 2 y (63–77%) | HR 0.83 (95% CI 0.53–1.31)Non-inferiority also met in the intention-to-treat analysis (one-sided 95% boundary 6% lower). The frequency of postoperative complications and postoperative mortality after standard surgery or postponed surgery after active surveillance was reported as similar between groups. |
| Endpoint | Analysis | Active surveillance | Standard surgery | Effect |
|---|---|---|---|---|
| OSModified intention-to-treat (crossover allowed at the time of clinical complete response) | primarymedian follow-up 38 monthsvan 2025 | 74% at 2 y (69–78%) | 71% at 2 y (62–78%) | HR 1.14 (95% CI 0.74–1.78)Non-inferiority was met: the one-sided 95% boundary was 7% lower (margin 15%). The abstract gives no P value for the survival comparison and states no significant difference in overall survival. The abstract does not state which arm is the numerator of the hazard ratios (1.14 modified intention-to-treat, 0.83 intention-to-treat). |
| OSIntention-to-treat | primarymedian follow-up 38 monthsvan 2025 | 75% at 2 y (68–80%) | 70% at 2 y (63–77%) | HR 0.83 (95% CI 0.53–1.31)Non-inferiority also met in the intention-to-treat analysis (one-sided 95% boundary 6% lower). The frequency of postoperative complications and postoperative mortality after standard surgery or postponed surgery after active surveillance was reported as similar between groups. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 1.14 | 0.74–1.78 |
| OS | 0.83 | 0.53–1.31 |
Appears in
Sources
van der Wilk BJ, Eyck BM, Wijnhoven BPL, Lagarde SM, Rosman C, Noordman BJ, et al. Neoadjuvant chemoradiotherapy followed by active surveillance versus standard surgery for oesophageal cancer (SANO trial): a multicentre, stepped-wedge, cluster-randomised, non-inferiority, phase 3 trial. Lancet Oncol. 2025;26(4):425-436.