Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed: The Study Protocol for the Randomized Controlled NEEDS Trial

Magnus Nilsson, Halla Olafsdottir, Gabriella Alexandersson von Döbeln, Fernanda Villegas, Giovanna Gagliardi, Mats Hellström, Qiao-Li Wang, Hemming Johansson, Val Gebski, Jakob Hedberg, Fredrik Klevebro, Sheraz Markar, Elizabeth Smyth, Pernilla Lagergren, Ghazwan Al-Haidari, Lars Cato Rekstad, Eirik Kjus Aahlin, Bengt Wallner, David Edholm, Jan Johansson, Eva Szabo, John V Reynolds, C S Pramesh, Naveen Mummudi, Amit Joshi, Lorenzo Ferri, Rebecca Ks Wong, Chris O'Callaghan, Jelena Lukovic, Kelvin Kw Chan, Trevor Leong, Andrew Barbour, Mark Smithers, Yin Li, Xiaozheng Kang, Feng-Ming Kong, Yin-Kai Chao, Tom Crosby, Christiane Bruns, Hanneke van Laarhoven, Mark van Berge Henegouwen, Richard van Hillegersberg, Riccardo Rosati, Guillaume Piessen, Giovanni de Manzoni, Florian Lordick, Magnus Nilsson, Halla Olafsdottir, Gabriella Alexandersson von Döbeln, Fernanda Villegas, Giovanna Gagliardi, Mats Hellström, Qiao-Li Wang, Hemming Johansson, Val Gebski, Jakob Hedberg, Fredrik Klevebro, Sheraz Markar, Elizabeth Smyth, Pernilla Lagergren, Ghazwan Al-Haidari, Lars Cato Rekstad, Eirik Kjus Aahlin, Bengt Wallner, David Edholm, Jan Johansson, Eva Szabo, John V Reynolds, C S Pramesh, Naveen Mummudi, Amit Joshi, Lorenzo Ferri, Rebecca Ks Wong, Chris O'Callaghan, Jelena Lukovic, Kelvin Kw Chan, Trevor Leong, Andrew Barbour, Mark Smithers, Yin Li, Xiaozheng Kang, Feng-Ming Kong, Yin-Kai Chao, Tom Crosby, Christiane Bruns, Hanneke van Laarhoven, Mark van Berge Henegouwen, Richard van Hillegersberg, Riccardo Rosati, Guillaume Piessen, Giovanni de Manzoni, Florian Lordick

Abstract

Background: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC.

Methods: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up.

Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT04460352.

Keywords: definitive chemoradiotherapy; esophageal squamous cell carcinoma; locoregional surveillance; neoadjuvant chemoradiotherapy; salvage esophagectomy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Nilsson, Olafsdottir, Alexandersson von Döbeln, Villegas, Gagliardi, Hellström, Wang, Johansson, Gebski, Hedberg, Klevebro, Markar, Smyth, Lagergren, Al-Haidari, Rekstad, Aahlin, Wallner, Edholm, Johansson, Szabo, Reynolds, Pramesh, Mummudi, Joshi, Ferri, Wong, O’Callaghan, Lukovic, Chan, Leong, Barbour, Smithers, Li, Kang, Kong, Chao, Crosby, Bruns, van Laarhoven, van Berge Henegouwen, van Hillegersberg, Rosati, Piessen, de Manzoni and Lordick.

Figures

Figure 1
Figure 1
NEEDS randomization overview.
Figure 2
Figure 2
Overview of scheduled cancer recurrence surveillance by treatment allocation.

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