Prolonged Time to Surgery in Patients with Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer

Hidde C G Overtoom; Ben M Eyck; Berend J van der Wilk; SANO study group; Bo J Noordman; Pieter C van der Sluis; Bas P L Wijnhoven; J Jan B van Lanschot; Sjoerd M Lagarde

doi:10.1097/SLA.0000000000006488

Prolonged Time to Surgery in Patients with Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer

Surgery

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Abstract

OBJECTIVE: To investigate whether prolonged time to surgery negatively affects survival, pathological outcome or postoperative complications in patients with histologically proven residual disease after neoadjuvant chemoradiotherapy for locally advanced esophageal cancer.

SUMMARY BACKGROUND DATA: Historically, the standard time to surgery (TTS) has been six to eight weeks after completion of nCRT. The effect of prolonged TTS is gaining interest, with contradicting results on survival and surgical morbidity. It can be hypothesized that, in patients with residual disease six weeks after completion of nCRT, prolonged TTS might be associated with worse survival and higher morbidity.

METHODS: Patients with locally advanced esophageal cancer who had biopsy-proven residual disease six weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs. TTS≤12w). Primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathological outcomes, and postoperative complications. Multivariable Cox regression was used for comparing survival and logistic regression for other outcomes, adjusted for the confounders age, cT, cN, Charlson comorbidity index, weight loss during nCRT, and WHO performance score after completion of nCRT.

RESULTS: Forty patients were included for TTS>12w and 127 for TTS≤12w. TTS>12w was associated with better overall survival (adjusted hazard ratio (aHR) 0.46, 95%CI 0.24-0.90), and disease-free survival (aHR 0.48, 95%CI 0.24-0.94), but also with more postoperative respiratory complications (aOR 3.66, 95%CI 1.52-9.59). Other outcomes were comparable between both groups.

CONCLUSION: Prolonged TTS in patients with histologically proven residual disease after completion of nCRT for esophageal cancer did not have a negative effect on overall and disease-free survival, but patients did have a higher risk for postoperative respiratory complications.

Original language	English
Article number	10.1097/SLA.0000000000006488
Pages (from-to)	268-276
Number of pages	9
Journal	Annals of Surgery
Volume	283
Issue number	2
Early online date	13 Aug 2024
DOIs	https://doi.org/10.1097/SLA.0000000000006488
Publication status	Published - Feb 2026

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prolonged_time_to_surgery_in_patients_with.1027Accepted author manuscript, 547 KBLicence: CC BY

Cite this

Overtoom, H. C. G., Eyck, B. M., van der Wilk, B. J., SANO study group, Noordman, B. J., van der Sluis, P. C., Wijnhoven, B. P. L., van Lanschot, J. J. B., & Lagarde, S. M. (2026). Prolonged Time to Surgery in Patients with Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer. Annals of Surgery, 283(2), 268-276. Article 10.1097/SLA.0000000000006488. https://doi.org/10.1097/SLA.0000000000006488

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title = "Prolonged Time to Surgery in Patients with Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer",

abstract = "OBJECTIVE: To investigate whether prolonged time to surgery negatively affects survival, pathological outcome or postoperative complications in patients with histologically proven residual disease after neoadjuvant chemoradiotherapy for locally advanced esophageal cancer.SUMMARY BACKGROUND DATA: Historically, the standard time to surgery (TTS) has been six to eight weeks after completion of nCRT. The effect of prolonged TTS is gaining interest, with contradicting results on survival and surgical morbidity. It can be hypothesized that, in patients with residual disease six weeks after completion of nCRT, prolonged TTS might be associated with worse survival and higher morbidity.METHODS: Patients with locally advanced esophageal cancer who had biopsy-proven residual disease six weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs. TTS≤12w). Primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathological outcomes, and postoperative complications. Multivariable Cox regression was used for comparing survival and logistic regression for other outcomes, adjusted for the confounders age, cT, cN, Charlson comorbidity index, weight loss during nCRT, and WHO performance score after completion of nCRT.RESULTS: Forty patients were included for TTS>12w and 127 for TTS≤12w. TTS>12w was associated with better overall survival (adjusted hazard ratio (aHR) 0.46, 95\%CI 0.24-0.90), and disease-free survival (aHR 0.48, 95\%CI 0.24-0.94), but also with more postoperative respiratory complications (aOR 3.66, 95\%CI 1.52-9.59). Other outcomes were comparable between both groups.CONCLUSION: Prolonged TTS in patients with histologically proven residual disease after completion of nCRT for esophageal cancer did not have a negative effect on overall and disease-free survival, but patients did have a higher risk for postoperative respiratory complications.",

author = "Overtoom, \{Hidde C G\} and Eyck, \{Ben M\} and \{van der Wilk\}, \{Berend J\} and \{SANO study group\} and Noordman, \{Bo J\} and \{van der Sluis\}, \{Pieter C\} and Wijnhoven, \{Bas P L\} and \{van Lanschot\}, \{J Jan B\} and Lagarde, \{Sjoerd M\}",

note = "Copyright {\textcopyright} 2024 The Author(s). Published by Wolters Kluwer Health, Inc.",

year = "2026",

month = feb,

doi = "10.1097/SLA.0000000000006488",

language = "English",

volume = "283",

pages = "268--276",

journal = "Annals of Surgery",

issn = "0003-4932",

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Overtoom, HCG, Eyck, BM, van der Wilk, BJ, SANO study group, Noordman, BJ , van der Sluis, PC , Wijnhoven, BPL , van Lanschot, JJB & Lagarde, SM 2026, 'Prolonged Time to Surgery in Patients with Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer', Annals of Surgery, vol. 283, no. 2, 10.1097/SLA.0000000000006488, pp. 268-276. https://doi.org/10.1097/SLA.0000000000006488

TY - JOUR

T1 - Prolonged Time to Surgery in Patients with Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer

AU - Overtoom, Hidde C G

AU - Eyck, Ben M

AU - van der Wilk, Berend J

AU - SANO study group

AU - Noordman, Bo J

AU - van der Sluis, Pieter C

AU - Wijnhoven, Bas P L

AU - van Lanschot, J Jan B

AU - Lagarde, Sjoerd M

PY - 2026/2

Y1 - 2026/2

N2 - OBJECTIVE: To investigate whether prolonged time to surgery negatively affects survival, pathological outcome or postoperative complications in patients with histologically proven residual disease after neoadjuvant chemoradiotherapy for locally advanced esophageal cancer.SUMMARY BACKGROUND DATA: Historically, the standard time to surgery (TTS) has been six to eight weeks after completion of nCRT. The effect of prolonged TTS is gaining interest, with contradicting results on survival and surgical morbidity. It can be hypothesized that, in patients with residual disease six weeks after completion of nCRT, prolonged TTS might be associated with worse survival and higher morbidity.METHODS: Patients with locally advanced esophageal cancer who had biopsy-proven residual disease six weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs. TTS≤12w). Primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathological outcomes, and postoperative complications. Multivariable Cox regression was used for comparing survival and logistic regression for other outcomes, adjusted for the confounders age, cT, cN, Charlson comorbidity index, weight loss during nCRT, and WHO performance score after completion of nCRT.RESULTS: Forty patients were included for TTS>12w and 127 for TTS≤12w. TTS>12w was associated with better overall survival (adjusted hazard ratio (aHR) 0.46, 95%CI 0.24-0.90), and disease-free survival (aHR 0.48, 95%CI 0.24-0.94), but also with more postoperative respiratory complications (aOR 3.66, 95%CI 1.52-9.59). Other outcomes were comparable between both groups.CONCLUSION: Prolonged TTS in patients with histologically proven residual disease after completion of nCRT for esophageal cancer did not have a negative effect on overall and disease-free survival, but patients did have a higher risk for postoperative respiratory complications.

AB - OBJECTIVE: To investigate whether prolonged time to surgery negatively affects survival, pathological outcome or postoperative complications in patients with histologically proven residual disease after neoadjuvant chemoradiotherapy for locally advanced esophageal cancer.SUMMARY BACKGROUND DATA: Historically, the standard time to surgery (TTS) has been six to eight weeks after completion of nCRT. The effect of prolonged TTS is gaining interest, with contradicting results on survival and surgical morbidity. It can be hypothesized that, in patients with residual disease six weeks after completion of nCRT, prolonged TTS might be associated with worse survival and higher morbidity.METHODS: Patients with locally advanced esophageal cancer who had biopsy-proven residual disease six weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs. TTS≤12w). Primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathological outcomes, and postoperative complications. Multivariable Cox regression was used for comparing survival and logistic regression for other outcomes, adjusted for the confounders age, cT, cN, Charlson comorbidity index, weight loss during nCRT, and WHO performance score after completion of nCRT.RESULTS: Forty patients were included for TTS>12w and 127 for TTS≤12w. TTS>12w was associated with better overall survival (adjusted hazard ratio (aHR) 0.46, 95%CI 0.24-0.90), and disease-free survival (aHR 0.48, 95%CI 0.24-0.94), but also with more postoperative respiratory complications (aOR 3.66, 95%CI 1.52-9.59). Other outcomes were comparable between both groups.CONCLUSION: Prolonged TTS in patients with histologically proven residual disease after completion of nCRT for esophageal cancer did not have a negative effect on overall and disease-free survival, but patients did have a higher risk for postoperative respiratory complications.

UR - https://www.scopus.com/pages/publications/85201661008

U2 - 10.1097/SLA.0000000000006488

DO - 10.1097/SLA.0000000000006488

M3 - Article

C2 - 39140597

SN - 0003-4932

VL - 283

SP - 268

EP - 276

JO - Annals of Surgery

JF - Annals of Surgery

IS - 2

M1 - 10.1097/SLA.0000000000006488

ER -

Prolonged Time to Surgery in Patients with Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer

Abstract

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