TY - JOUR
T1 - Neoadjuvant chemoradiotherapy followed by active surveillance versus standard surgery for oesophageal cancer (SANO trial)
T2 - a multicentre, stepped-wedge, cluster-randomised, non-inferiority, phase 3 trial
AU - van der Wilk, Berend J.
AU - Eyck, Ben M.
AU - SANO study group
AU - Wijnhoven, Bas P.L.
AU - Lagarde, Sjoerd M.
AU - Rosman, Camiel
AU - Noordman, Bo J.
AU - Valkema, Maria J.
AU - Bisseling, Tanya M.
AU - Coene, Peter Paul L.O.
AU - van Det, Marc J.
AU - Dekker, Jan Willem T.
AU - van Dieren, Jolanda M.
AU - Doukas, Michail
AU - van Esser, Stijn
AU - Fiets, W. Edward
AU - Hartgrink, Henk H.
AU - Heisterkamp, Joos
AU - Holster, I. Lisanne
AU - Klarenbeek, Bastiaan
AU - van Klaveren, David
AU - Kouw, Eva
AU - Kouwenhoven, Ewout A.
AU - Luyer, Misha D.
AU - Mostert, Bianca
AU - Nieuwenhuijzen, Grard A.P.
AU - Oostenbrug, Liekele E.
AU - Pierie, Jean Pierre E.N.
AU - van Sandick, Johanna W.
AU - Sosef, Meindert N.
AU - Spaander, Manon C.W.
AU - Valkema, Roelf
AU - van der Zaag, Edwin S.
AU - Steyerberg, Ewout W.
AU - van Lanschot, J. Jan B.
AU - Koch, Arjun D.
AU - Nikkessen, Suzan
AU - van der Gaast, Ate
AU - de Lussanet de la Sablonière, Quido G.
AU - Biermann, Katharina
AU - Oudijk, Lindsey
AU - Lingsma, Hester F.
AU - Dwarkasing, Roy S.
AU - Nuyttens, Joost J.
AU - Gangaram-Panday, Sanjiv
AU - van der Sluis, Pieter C.
AU - Siersema, Peter D.
AU - Zweers, Serge J.
AU - Hol, Lieke
AU - Aktas, Huseyin
AU - Quispel, Rutger
AU - ten Broek, Marc R.J.
AU - Muller, Karin
AU - Creemers, Geert Jan
AU - Soufidi, Khalida
AU - Slingerland, Marije
N1 - Publisher Copyright:
© 2025 Elsevier Ltd
PY - 2025/4
Y1 - 2025/4
N2 - Background: A substantial proportion of individuals with oesophageal cancer have a pathological complete response after neoadjuvant chemoradiotherapy and oesophagectomy. We aimed to investigate whether active surveillance could be an alternative for individuals with a clinical complete response after neoadjuvant chemoradiotherapy. Methods: We performed a multicentre, stepped-wedge, cluster-randomised, non-inferiority, phase 3 trial in 12 Dutch hospitals. Individuals with locally advanced oesophageal cancer and a clinical complete response after neoadjuvant chemoradiotherapy (ie, no tumour detected with endoscopic biopsies, ultrasound, and PET-CT) underwent active surveillance or standard surgery (ie, oesophagectomy within 2 weeks after reaching clinical complete response). There were no inclusion restrictions regarding comorbidities or performance status, but participants had carcinoma, were age 18 years or older, and were treated with curative intent. Randomisation of hospitals was performed using computer-generated sequences without stratification methods, after an initial phase of all hospitals performing standard surgery. The primary endpoint was overall survival, analysed according to a modified intention-to-treat principle (allowing crossover at time of clinical complete response) and an intention-to-treat principle. Non-inferiority was defined as 2-year survival rate for active surveillance of 15% or less below that for standard surgery. The trial was registered within the Netherlands Trial Register, NTR-6803, and the inclusion phase has been completed.Findings: Between Nov 8, 2017, and Jan 17, 2021, 1115 individuals were screened, of whom 309 were included. 198 underwent active surveillance and 111 underwent standard surgery. 242 (78%) participants were male and 67 (22%) were female. Median follow-up was 38 months (IQR 32–48). 2-year overall survival for active surveillance (74% [95% CI 69–78]) was non-inferior to standard surgery (71% [62–78]) after modified intention-to-treat analysis (one-sided 95% boundary: 7% lower). It remained non-inferior in the intention-to-treat analysis (75% [68–80] vs 70% [63–77], one-sided 95% boundary: 6% lower). There were no significant differences in overall survival according to modified intention-to-treat analysis (hazard ratio 1·14, two-sided 95% CI 0·74–1·78) or intention-to-treat analysis (0·83, 0·53–1·31). The frequency of postoperative complications and postoperative mortality after standard surgery or postponed surgery after active surveillance was similar between groups. Interpretation: Overall survival after active surveillance for oesophageal cancer was non-inferior 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 counselling and shared decision making.
AB - Background: A substantial proportion of individuals with oesophageal cancer have a pathological complete response after neoadjuvant chemoradiotherapy and oesophagectomy. We aimed to investigate whether active surveillance could be an alternative for individuals with a clinical complete response after neoadjuvant chemoradiotherapy. Methods: We performed a multicentre, stepped-wedge, cluster-randomised, non-inferiority, phase 3 trial in 12 Dutch hospitals. Individuals with locally advanced oesophageal cancer and a clinical complete response after neoadjuvant chemoradiotherapy (ie, no tumour detected with endoscopic biopsies, ultrasound, and PET-CT) underwent active surveillance or standard surgery (ie, oesophagectomy within 2 weeks after reaching clinical complete response). There were no inclusion restrictions regarding comorbidities or performance status, but participants had carcinoma, were age 18 years or older, and were treated with curative intent. Randomisation of hospitals was performed using computer-generated sequences without stratification methods, after an initial phase of all hospitals performing standard surgery. The primary endpoint was overall survival, analysed according to a modified intention-to-treat principle (allowing crossover at time of clinical complete response) and an intention-to-treat principle. Non-inferiority was defined as 2-year survival rate for active surveillance of 15% or less below that for standard surgery. The trial was registered within the Netherlands Trial Register, NTR-6803, and the inclusion phase has been completed.Findings: Between Nov 8, 2017, and Jan 17, 2021, 1115 individuals were screened, of whom 309 were included. 198 underwent active surveillance and 111 underwent standard surgery. 242 (78%) participants were male and 67 (22%) were female. Median follow-up was 38 months (IQR 32–48). 2-year overall survival for active surveillance (74% [95% CI 69–78]) was non-inferior to standard surgery (71% [62–78]) after modified intention-to-treat analysis (one-sided 95% boundary: 7% lower). It remained non-inferior in the intention-to-treat analysis (75% [68–80] vs 70% [63–77], one-sided 95% boundary: 6% lower). There were no significant differences in overall survival according to modified intention-to-treat analysis (hazard ratio 1·14, two-sided 95% CI 0·74–1·78) or intention-to-treat analysis (0·83, 0·53–1·31). The frequency of postoperative complications and postoperative mortality after standard surgery or postponed surgery after active surveillance was similar between groups. Interpretation: Overall survival after active surveillance for oesophageal cancer was non-inferior 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 counselling and shared decision making.
UR - http://www.scopus.com/inward/record.url?scp=105001507382&partnerID=8YFLogxK
U2 - 10.1016/s1470-2045(25)00027-0
DO - 10.1016/s1470-2045(25)00027-0
M3 - Article
C2 - 40112851
AN - SCOPUS:105001507382
SN - 1470-2045
VL - 26
SP - 425
EP - 436
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 4
ER -