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. 2026 Feb 1;283(2):268-276.
doi: 10.1097/SLA.0000000000006488. Epub 2024 Aug 13.

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

Hidde C G Overtoom  1 , Ben M Eyck, Berend J van der Wilk, Bo J Noordman, Pieter C van der Sluis, Bas P L Wijnhoven, J Jan B van Lanschot, Sjoerd M Lagarde; SANO study group*
Affiliations

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

Hidde C G Overtoom et al. Ann Surg. .

Abstract

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

Background: Historically, the standard time to surgery (TTS) has been 6 to 8 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 6 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 6 weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs TTS≤12w). The primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathologic 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.

Conclusions: 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.

Keywords: esophageal cancer; neoadjuvant chemoradiotherapy; prolonged time to surgery; residual disease.

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Conflict of interest statement

The authors report no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart of patients who had residual tumor in endoscopic biopsies take 4 to 6 weeks after completion of neoadjuvant chemoradiotherapy according to the CROSS regimen.
FIGURE 2
FIGURE 2
Overall survival (A) and disease-free survival (B) with 95% CIs of patients with histologically proven residual tumor 6 weeks after completion of nCRT, stratified by time to surgery (TTS) of >12 weeks and ≤12 weeks after completion of nCRT.
See this image and copyright information in PMC

References

    1. Lordick F, Mariette C, Haustermans K, et al. Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v50–v57. - PubMed
    1. Shah MA, Kennedy EB, Catenacci DV, et al. Treatment of locally advanced esophageal carcinoma: ASCO guideline. J Clin Oncol. 2020;38:2677–2694. - PubMed
    1. Kim JY, Correa AM, Vaporciyan AA, et al. Does the timing of esophagectomy after chemoradiation affect outcome? Ann Thorac Surg. 2012;93:207–213. - PMC - PubMed
    1. Nilsson K, Klevebro F, Rouvelas I, et al. Surgical morbidity and mortality from the Multicenter Randomized Controlled NeoRes II Trial: standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for esophageal cancer. Ann Surg. 2020;272:684–689. - PubMed
    1. Nilsson K, Klevebro F, Sunde B, et al. Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial. Ann Oncol. 2023;34:1015–1024. - PubMed

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