Detecting residual disease after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma: The prospective multicentre preSINO trial

Yang Yang; Zhichao Liu; Ian Wong; Xing Gao; Hong Zhang; Jun Liu; Ben M. Eyck; Jinchen Shao; Yuchen Han; Berend J. van der Wilk; Yinkai Chao; Simon Law; Bas P.L. Wijnhoven; J. Jan B. van Lanschot; Zhigang Li

doi:10.1093/bjs/znaf004

Detecting residual disease after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma: The prospective multicentre preSINO trial

Yang Yang, Zhichao Liu, Ian Wong, Xing Gao, Hong Zhang, Jun Liu, Ben M. Eyck, Jinchen Shao, Yuchen Han, Berend J. van der Wilk, Yinkai Chao, Simon Law, Bas P.L. Wijnhoven, J. Jan B. van Lanschot, Zhigang Li^*

^*Corresponding author for this work

Surgery

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Abstract

BACKGROUND:

Neoadjuvant chemoradiotherapy (nCRT) in patients with oesophageal squamous cell carcinoma (OSCC) may lead to clinical complete response (cCR). It is important to know the accuracy of clinical response evaluations (CREs) before advocating active surveillance instead of oesophagectomy.

METHODS:

This was a prospective, multicentre study of patients with locally advanced OSCC. They received the first CRE (bite-on-bite biopsies) 4-6 weeks after nCRT. Patients with residual tumour underwent surgery. Patients with a cCR at CRE-1 underwent a second CRE 10-12 weeks after nCRT using PET-CT, bite-on-bite biopsies and endoscopic ultrasound fine-needle aspiration (EUS-FNA). All patients without distant metastases underwent surgery. Primary endpoint was the accuracy of CREs for detecting Tumour Regression Grade (TRG)3-4 or TRG1-2 with ypN+ residual tumour with a prespecified false-negative rate (FNR) of 19.5%. Circulating-tumour DNA (ctDNA) at CREs was performed for exploratory analysis.

RESULTS:

In total 309 patients were included. Eighteen of 133 patients with TRG3-4 or TRG1-2 with ypN+ residual tumours were not detected by bite-on-bite biopsies and EUS-FNA (FNR: 13.5%). Sensitivity, specificity, negative predictive value and positive predictive value of detecting any residual tumour were 81.7%, 93.2%, 68.7% and 96.5% respectively. PET-CT detected interval distant metastases in 13 (4.9%) of 268 patients presurgically. After a minimum 12-month follow-up, systemic recurrence rates were 28.0% in patients with positive ctDNA at CREs and 5.3% in those with negative ctDNA.

CONCLUSIONS:

Bite-on-bite biopsies and EUS-FNA were accurate in detecting residual disease after nCRT in OSCC. Positive ctDNA at CREs may indicate an increased risk of systemic metastases.

Original language	English
Article number	znaf004
Journal	The British journal of surgery
Volume	112
Issue number	2
DOIs	https://doi.org/10.1093/bjs/znaf004
Publication status	Published - Feb 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025. Published by Oxford University Press on behalf of BJS Foundation Ltd.

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10.1093/bjs/znaf004Licence: CC BY-NC

Detecting residual disease after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinomaFinal published version, 312 KBLicence: CC BY-NC

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Yang, Y., Liu, Z., Wong, I., Gao, X., Zhang, H., Liu, J., Eyck, B. M., Shao, J., Han, Y., van der Wilk, B. J., Chao, Y., Law, S., Wijnhoven, B. P. L., van Lanschot, J. J. B., & Li, Z. (2025). Detecting residual disease after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma: The prospective multicentre preSINO trial. The British journal of surgery, 112(2), Article znaf004. https://doi.org/10.1093/bjs/znaf004

@article{3c44325c9ae44959a0f6e713ce5ea2b3,

title = "Detecting residual disease after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma: The prospective multicentre preSINO trial",

abstract = "BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) in patients with oesophageal squamous cell carcinoma (OSCC) may lead to clinical complete response (cCR). It is important to know the accuracy of clinical response evaluations (CREs) before advocating active surveillance instead of oesophagectomy. METHODS: This was a prospective, multicentre study of patients with locally advanced OSCC. They received the first CRE (bite-on-bite biopsies) 4-6 weeks after nCRT. Patients with residual tumour underwent surgery. Patients with a cCR at CRE-1 underwent a second CRE 10-12 weeks after nCRT using PET-CT, bite-on-bite biopsies and endoscopic ultrasound fine-needle aspiration (EUS-FNA). All patients without distant metastases underwent surgery. Primary endpoint was the accuracy of CREs for detecting Tumour Regression Grade (TRG)3-4 or TRG1-2 with ypN+ residual tumour with a prespecified false-negative rate (FNR) of 19.5%. Circulating-tumour DNA (ctDNA) at CREs was performed for exploratory analysis. RESULTS: In total 309 patients were included. Eighteen of 133 patients with TRG3-4 or TRG1-2 with ypN+ residual tumours were not detected by bite-on-bite biopsies and EUS-FNA (FNR: 13.5%). Sensitivity, specificity, negative predictive value and positive predictive value of detecting any residual tumour were 81.7%, 93.2%, 68.7% and 96.5% respectively. PET-CT detected interval distant metastases in 13 (4.9%) of 268 patients presurgically. After a minimum 12-month follow-up, systemic recurrence rates were 28.0% in patients with positive ctDNA at CREs and 5.3% in those with negative ctDNA. CONCLUSIONS: Bite-on-bite biopsies and EUS-FNA were accurate in detecting residual disease after nCRT in OSCC. Positive ctDNA at CREs may indicate an increased risk of systemic metastases.",

author = "Yang Yang and Zhichao Liu and Ian Wong and Xing Gao and Hong Zhang and Jun Liu and Eyck, {Ben M.} and Jinchen Shao and Yuchen Han and {van der Wilk}, {Berend J.} and Yinkai Chao and Simon Law and Wijnhoven, {Bas P.L.} and {van Lanschot}, {J. Jan B.} and Zhigang Li",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025. Published by Oxford University Press on behalf of BJS Foundation Ltd.",

year = "2025",

month = feb,

doi = "10.1093/bjs/znaf004",

language = "English",

volume = "112",

journal = "The British journal of surgery",

issn = "0007-1323",

publisher = "Oxford University Press",

number = "2",

}

Yang, Y, Liu, Z, Wong, I, Gao, X, Zhang, H, Liu, J, Eyck, BM, Shao, J, Han, Y, van der Wilk, BJ, Chao, Y, Law, S, Wijnhoven, BPL , van Lanschot, JJB & Li, Z 2025, 'Detecting residual disease after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma: The prospective multicentre preSINO trial', The British journal of surgery, vol. 112, no. 2, znaf004. https://doi.org/10.1093/bjs/znaf004

TY - JOUR

T1 - Detecting residual disease after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma

T2 - The prospective multicentre preSINO trial

AU - Yang, Yang

AU - Liu, Zhichao

AU - Wong, Ian

AU - Gao, Xing

AU - Zhang, Hong

AU - Liu, Jun

AU - Eyck, Ben M.

AU - Shao, Jinchen

AU - Han, Yuchen

AU - van der Wilk, Berend J.

AU - Chao, Yinkai

AU - Law, Simon

AU - Wijnhoven, Bas P.L.

AU - van Lanschot, J. Jan B.

AU - Li, Zhigang

PY - 2025/2

Y1 - 2025/2

N2 - BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) in patients with oesophageal squamous cell carcinoma (OSCC) may lead to clinical complete response (cCR). It is important to know the accuracy of clinical response evaluations (CREs) before advocating active surveillance instead of oesophagectomy. METHODS: This was a prospective, multicentre study of patients with locally advanced OSCC. They received the first CRE (bite-on-bite biopsies) 4-6 weeks after nCRT. Patients with residual tumour underwent surgery. Patients with a cCR at CRE-1 underwent a second CRE 10-12 weeks after nCRT using PET-CT, bite-on-bite biopsies and endoscopic ultrasound fine-needle aspiration (EUS-FNA). All patients without distant metastases underwent surgery. Primary endpoint was the accuracy of CREs for detecting Tumour Regression Grade (TRG)3-4 or TRG1-2 with ypN+ residual tumour with a prespecified false-negative rate (FNR) of 19.5%. Circulating-tumour DNA (ctDNA) at CREs was performed for exploratory analysis. RESULTS: In total 309 patients were included. Eighteen of 133 patients with TRG3-4 or TRG1-2 with ypN+ residual tumours were not detected by bite-on-bite biopsies and EUS-FNA (FNR: 13.5%). Sensitivity, specificity, negative predictive value and positive predictive value of detecting any residual tumour were 81.7%, 93.2%, 68.7% and 96.5% respectively. PET-CT detected interval distant metastases in 13 (4.9%) of 268 patients presurgically. After a minimum 12-month follow-up, systemic recurrence rates were 28.0% in patients with positive ctDNA at CREs and 5.3% in those with negative ctDNA. CONCLUSIONS: Bite-on-bite biopsies and EUS-FNA were accurate in detecting residual disease after nCRT in OSCC. Positive ctDNA at CREs may indicate an increased risk of systemic metastases.

AB - BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) in patients with oesophageal squamous cell carcinoma (OSCC) may lead to clinical complete response (cCR). It is important to know the accuracy of clinical response evaluations (CREs) before advocating active surveillance instead of oesophagectomy. METHODS: This was a prospective, multicentre study of patients with locally advanced OSCC. They received the first CRE (bite-on-bite biopsies) 4-6 weeks after nCRT. Patients with residual tumour underwent surgery. Patients with a cCR at CRE-1 underwent a second CRE 10-12 weeks after nCRT using PET-CT, bite-on-bite biopsies and endoscopic ultrasound fine-needle aspiration (EUS-FNA). All patients without distant metastases underwent surgery. Primary endpoint was the accuracy of CREs for detecting Tumour Regression Grade (TRG)3-4 or TRG1-2 with ypN+ residual tumour with a prespecified false-negative rate (FNR) of 19.5%. Circulating-tumour DNA (ctDNA) at CREs was performed for exploratory analysis. RESULTS: In total 309 patients were included. Eighteen of 133 patients with TRG3-4 or TRG1-2 with ypN+ residual tumours were not detected by bite-on-bite biopsies and EUS-FNA (FNR: 13.5%). Sensitivity, specificity, negative predictive value and positive predictive value of detecting any residual tumour were 81.7%, 93.2%, 68.7% and 96.5% respectively. PET-CT detected interval distant metastases in 13 (4.9%) of 268 patients presurgically. After a minimum 12-month follow-up, systemic recurrence rates were 28.0% in patients with positive ctDNA at CREs and 5.3% in those with negative ctDNA. CONCLUSIONS: Bite-on-bite biopsies and EUS-FNA were accurate in detecting residual disease after nCRT in OSCC. Positive ctDNA at CREs may indicate an increased risk of systemic metastases.

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U2 - 10.1093/bjs/znaf004

DO - 10.1093/bjs/znaf004

M3 - Article

C2 - 39937490

AN - SCOPUS:85218476067

SN - 0007-1323

VL - 112

JO - The British journal of surgery

JF - The British journal of surgery

IS - 2

M1 - znaf004

ER -

Detecting residual disease after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma: The prospective multicentre preSINO trial

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