Definition of resectable stage III non-small cell lung cancer (NSCLC) for inclusion in clinical trials: A clinical case review by a pan-European multidisciplinary expert panel led by the EORTC Lung Cancer Group

Mariana Brandão; Elena Prisciandaro; Eleni Xenophontos; Alessio Mariolo; Amir H Sadeghi; Andrea R Filippi; Antonin Levy; Artur Bandura; Caroline Caramella; Chris Dickhoff; Constance de Margerie-Mellon; Corinne Faivre-Finn; Daniel Portik; David Sanchez-Lorente; Dirk De Ruysscher; Egbert Smit; Elisa Gobbini; Elie Fadel; Enrico Ruffini; Emanuela Olmetto; Francesco Cortiula; Idris Bahce; Ilias Houda; Isabelle Opitz; Jarushka Naidoo; John Edwards; Jordi Remon; José Carlos Benitez; Juan Carlos Trujillo; Jules Derks; Karim Amrane; Koen J Hartemink; Konstantinos Stathopoulos; Lizza E L Hendriks; Manoli Iglesias; Mario Occhipinti; Matthias Guckenberger; Niccolo Giaj Levra; Nicolas Girard; Noemi Reguart; Olaf Mercier; Paolo Bironzo; Paul Hofman; René Horsleben Petersen; Riccardo De Angelis; Ronan Abgral; Safae Terrisse; Sanjay Popat; Thomas Pierret; Torsten Gerriet Blum; European Organisation for Research, Treatment of Cancer EORTC Lung Cancer Group

doi:10.1016/j.lungcan.2025.108798

Definition of resectable stage III non-small cell lung cancer (NSCLC) for inclusion in clinical trials: A clinical case review by a pan-European multidisciplinary expert panel led by the EORTC Lung Cancer Group

Mariana Brandão^*, Elena Prisciandaro, Eleni Xenophontos, Alessio Mariolo, Amir H Sadeghi, Andrea R Filippi, Antonin Levy, Artur Bandura, Caroline Caramella, Chris Dickhoff, Constance de Margerie-Mellon, Corinne Faivre-Finn, Daniel Portik, David Sanchez-Lorente, Dirk De Ruysscher, Egbert Smit, Elisa Gobbini, Elie Fadel, Enrico Ruffini, Emanuela OlmettoFrancesco Cortiula, Idris Bahce, Ilias Houda, Isabelle Opitz, Jarushka Naidoo, John Edwards, Jordi Remon, José Carlos Benitez, Juan Carlos Trujillo, Jules Derks, Karim Amrane, Koen J Hartemink, Konstantinos Stathopoulos, Lizza E L Hendriks, Manoli Iglesias, Mario Occhipinti, Matthias Guckenberger, Niccolo Giaj Levra, Nicolas Girard, Noemi Reguart, Olaf Mercier, Paolo Bironzo, Paul Hofman, René Horsleben Petersen, Riccardo De Angelis, Ronan Abgral, Safae Terrisse, Sanjay Popat, Thomas Pierret, Torsten Gerriet Blum, European Organisation for Research, Treatment of Cancer EORTC Lung Cancer Group

^*Corresponding author for this work

Department of Cardiothoracic Surgery

5 Citations (Scopus)

Abstract

INTRODUCTION: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease, leading to ambiguity in resectability criteria. This has prompted the EORTC Lung Cancer Group to establish a standardized definition of resectability for clinical trials. A Delphi consensus process was initiated, including a systematic review, survey, and clinical cases review. Here, we report exclusively the results of the clinical cases review, aimed to categorize cases based on tumor and lymph node factors, to identify those deemed surgically resectable upfront.

METHODS: Consecutive patients with clinical stage III NSCLC (8th TNM edition) treated at Institut Jules Bordet between 2016-2021 were identified. These cases underwent evaluation by multidisciplinary panels (MDT), comprising thoracic surgeons, radiation oncologists, medical oncologists/pulmonologists and imaging specialists. The MDT determined the resectability of each tumor, and non-consensual cases underwent a second and a third discussion rounds. A TNM-subset was classified as "resectable" if ≥75 % of cases within that category were deemed "resectable" following multiple rounds of review.

RESULTS: Among 105 cases, 52 % of tumors were stage IIIA, 36 % stage IIIB and 11 % stage IIIC. After the first two review rounds, 13 % of cases were classified as "no consensus" and moved to a third round. The main reasons were suboptimal imaging (n = 8), incomplete invasive mediastinal staging to assess the N factor (n = 3), and disagreement on the resectability of T4 tumors invading thoracic structures or with multi-station/bulky N2 disease (n = 3). After the third review round, T3-T4 tumors based on size/satellite nodules and/or with N1-N2 single-station involvement were considered resectable. In contrast, many invasive T4-tumors were considered unresectable, especially if combined with N2-N3 disease. N2-multi-station, N2-bulky or N3 involvement were generally considered unresectable (100 %/95 %/95 % respectively).

CONCLUSIONS: After a multiple-round multidisciplinary review of real-world cases, consensus was reached for most TNM-subsets, except for invasive T4N0 tumors. This case review informed the Consensual Definition of Resectable stage III NSCLC in clinical trials.

Original language	English
Article number	108798
Journal	Lung Cancer
Volume	209
Pages (from-to)	108798
ISSN	0169-5002
DOIs	https://doi.org/10.1016/j.lungcan.2025.108798
Publication status	Published - 2025

Keywords

Lung cancer
Real-world
Resectable
Stage III
Surgery

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Brandão, M., Prisciandaro, E., Xenophontos, E., Mariolo, A., Sadeghi, A. H., Filippi, A. R., Levy, A., Bandura, A., Caramella, C., Dickhoff, C., de Margerie-Mellon, C., Faivre-Finn, C., Portik, D., Sanchez-Lorente, D., De Ruysscher, D., Smit, E., Gobbini, E., Fadel, E., Ruffini, E., ... European Organisation for Research, Treatment of Cancer EORTC Lung Cancer Group (2025). Definition of resectable stage III non-small cell lung cancer (NSCLC) for inclusion in clinical trials: A clinical case review by a pan-European multidisciplinary expert panel led by the EORTC Lung Cancer Group. Lung Cancer, 209, 108798. Article 108798. https://doi.org/10.1016/j.lungcan.2025.108798

Definition of resectable stage III non-small cell lung cancer (NSCLC) for inclusion in clinical trials: A clinical case review by a pan-European multidisciplinary expert panel led by the EORTC Lung Cancer Group. / Brandão, Mariana; Prisciandaro, Elena; Xenophontos, Eleni et al.
In: Lung Cancer, Vol. 209, 108798, 2025, p. 108798.

Research output: Contribution to journal › Journal article › Research › peer-review

Brandão, M, Prisciandaro, E, Xenophontos, E, Mariolo, A, Sadeghi, AH, Filippi, AR, Levy, A, Bandura, A, Caramella, C, Dickhoff, C, de Margerie-Mellon, C, Faivre-Finn, C, Portik, D, Sanchez-Lorente, D, De Ruysscher, D, Smit, E, Gobbini, E, Fadel, E, Ruffini, E, Olmetto, E, Cortiula, F, Bahce, I, Houda, I, Opitz, I, Naidoo, J, Edwards, J, Remon, J, Benitez, JC, Trujillo, JC, Derks, J, Amrane, K, Hartemink, KJ, Stathopoulos, K, Hendriks, LEL, Iglesias, M, Occhipinti, M, Guckenberger, M, Giaj Levra, N, Girard, N, Reguart, N, Mercier, O, Bironzo, P, Hofman, P, Petersen, RH, De Angelis, R, Abgral, R, Terrisse, S, Popat, S, Pierret, T, Blum, TG & European Organisation for Research, Treatment of Cancer EORTC Lung Cancer Group 2025, 'Definition of resectable stage III non-small cell lung cancer (NSCLC) for inclusion in clinical trials: A clinical case review by a pan-European multidisciplinary expert panel led by the EORTC Lung Cancer Group', Lung Cancer, vol. 209, 108798, pp. 108798. https://doi.org/10.1016/j.lungcan.2025.108798

Brandão M, Prisciandaro E, Xenophontos E, Mariolo A, Sadeghi AH, Filippi AR et al. Definition of resectable stage III non-small cell lung cancer (NSCLC) for inclusion in clinical trials: A clinical case review by a pan-European multidisciplinary expert panel led by the EORTC Lung Cancer Group. Lung Cancer. 2025;209:108798. 108798. Epub 2025 Oct 14. doi: 10.1016/j.lungcan.2025.108798

@article{b29b9997b47747db86f77887e33b28a1,

title = "Definition of resectable stage III non-small cell lung cancer (NSCLC) for inclusion in clinical trials: A clinical case review by a pan-European multidisciplinary expert panel led by the EORTC Lung Cancer Group",

abstract = "INTRODUCTION: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease, leading to ambiguity in resectability criteria. This has prompted the EORTC Lung Cancer Group to establish a standardized definition of resectability for clinical trials. A Delphi consensus process was initiated, including a systematic review, survey, and clinical cases review. Here, we report exclusively the results of the clinical cases review, aimed to categorize cases based on tumor and lymph node factors, to identify those deemed surgically resectable upfront.METHODS: Consecutive patients with clinical stage III NSCLC (8th TNM edition) treated at Institut Jules Bordet between 2016-2021 were identified. These cases underwent evaluation by multidisciplinary panels (MDT), comprising thoracic surgeons, radiation oncologists, medical oncologists/pulmonologists and imaging specialists. The MDT determined the resectability of each tumor, and non-consensual cases underwent a second and a third discussion rounds. A TNM-subset was classified as {"}resectable{"} if ≥75 \% of cases within that category were deemed {"}resectable{"} following multiple rounds of review.RESULTS: Among 105 cases, 52 \% of tumors were stage IIIA, 36 \% stage IIIB and 11 \% stage IIIC. After the first two review rounds, 13 \% of cases were classified as {"}no consensus{"} and moved to a third round. The main reasons were suboptimal imaging (n = 8), incomplete invasive mediastinal staging to assess the N factor (n = 3), and disagreement on the resectability of T4 tumors invading thoracic structures or with multi-station/bulky N2 disease (n = 3). After the third review round, T3-T4 tumors based on size/satellite nodules and/or with N1-N2 single-station involvement were considered resectable. In contrast, many invasive T4-tumors were considered unresectable, especially if combined with N2-N3 disease. N2-multi-station, N2-bulky or N3 involvement were generally considered unresectable (100 \%/95 \%/95 \% respectively).CONCLUSIONS: After a multiple-round multidisciplinary review of real-world cases, consensus was reached for most TNM-subsets, except for invasive T4N0 tumors. This case review informed the Consensual Definition of Resectable stage III NSCLC in clinical trials.",

keywords = "Lung cancer, Real-world, Resectable, Stage III, Surgery",

author = "Mariana Brand{\~a}o and Elena Prisciandaro and Eleni Xenophontos and Alessio Mariolo and Sadeghi, \{Amir H\} and Filippi, \{Andrea R\} and Antonin Levy and Artur Bandura and Caroline Caramella and Chris Dickhoff and \{de Margerie-Mellon\}, Constance and Corinne Faivre-Finn and Daniel Portik and David Sanchez-Lorente and \{De Ruysscher\}, Dirk and Egbert Smit and Elisa Gobbini and Elie Fadel and Enrico Ruffini and Emanuela Olmetto and Francesco Cortiula and Idris Bahce and Ilias Houda and Isabelle Opitz and Jarushka Naidoo and John Edwards and Jordi Remon and Benitez, \{Jos{\'e} Carlos\} and Trujillo, \{Juan Carlos\} and Jules Derks and Karim Amrane and Hartemink, \{Koen J\} and Konstantinos Stathopoulos and Hendriks, \{Lizza E L\} and Manoli Iglesias and Mario Occhipinti and Matthias Guckenberger and \{Giaj Levra\}, Niccolo and Nicolas Girard and Noemi Reguart and Olaf Mercier and Paolo Bironzo and Paul Hofman and Petersen, \{Ren{\'e} Horsleben\} and \{De Angelis\}, Riccardo and Ronan Abgral and Safae Terrisse and Sanjay Popat and Thomas Pierret and Blum, \{Torsten Gerriet\} and \{European Organisation for Research, Treatment of Cancer EORTC Lung Cancer Group\}",

note = "Copyright {\textcopyright} 2025. Published by Elsevier B.V.",

year = "2025",

doi = "10.1016/j.lungcan.2025.108798",

language = "English",

volume = "209",

pages = "108798",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Definition of resectable stage III non-small cell lung cancer (NSCLC) for inclusion in clinical trials

T2 - A clinical case review by a pan-European multidisciplinary expert panel led by the EORTC Lung Cancer Group

AU - Brandão, Mariana

AU - Prisciandaro, Elena

AU - Xenophontos, Eleni

AU - Mariolo, Alessio

AU - Sadeghi, Amir H

AU - Filippi, Andrea R

AU - Levy, Antonin

AU - Bandura, Artur

AU - Caramella, Caroline

AU - Dickhoff, Chris

AU - de Margerie-Mellon, Constance

AU - Faivre-Finn, Corinne

AU - Portik, Daniel

AU - Sanchez-Lorente, David

AU - De Ruysscher, Dirk

AU - Smit, Egbert

AU - Gobbini, Elisa

AU - Fadel, Elie

AU - Ruffini, Enrico

AU - Olmetto, Emanuela

AU - Cortiula, Francesco

AU - Bahce, Idris

AU - Houda, Ilias

AU - Opitz, Isabelle

AU - Naidoo, Jarushka

AU - Edwards, John

AU - Remon, Jordi

AU - Benitez, José Carlos

AU - Trujillo, Juan Carlos

AU - Derks, Jules

AU - Amrane, Karim

AU - Hartemink, Koen J

AU - Stathopoulos, Konstantinos

AU - Hendriks, Lizza E L

AU - Iglesias, Manoli

AU - Occhipinti, Mario

AU - Guckenberger, Matthias

AU - Giaj Levra, Niccolo

AU - Girard, Nicolas

AU - Reguart, Noemi

AU - Mercier, Olaf

AU - Bironzo, Paolo

AU - Hofman, Paul

AU - Petersen, René Horsleben

AU - De Angelis, Riccardo

AU - Abgral, Ronan

AU - Terrisse, Safae

AU - Popat, Sanjay

AU - Pierret, Thomas

AU - Blum, Torsten Gerriet

AU - European Organisation for Research, Treatment of Cancer EORTC Lung Cancer Group

PY - 2025

Y1 - 2025

N2 - INTRODUCTION: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease, leading to ambiguity in resectability criteria. This has prompted the EORTC Lung Cancer Group to establish a standardized definition of resectability for clinical trials. A Delphi consensus process was initiated, including a systematic review, survey, and clinical cases review. Here, we report exclusively the results of the clinical cases review, aimed to categorize cases based on tumor and lymph node factors, to identify those deemed surgically resectable upfront.METHODS: Consecutive patients with clinical stage III NSCLC (8th TNM edition) treated at Institut Jules Bordet between 2016-2021 were identified. These cases underwent evaluation by multidisciplinary panels (MDT), comprising thoracic surgeons, radiation oncologists, medical oncologists/pulmonologists and imaging specialists. The MDT determined the resectability of each tumor, and non-consensual cases underwent a second and a third discussion rounds. A TNM-subset was classified as "resectable" if ≥75 % of cases within that category were deemed "resectable" following multiple rounds of review.RESULTS: Among 105 cases, 52 % of tumors were stage IIIA, 36 % stage IIIB and 11 % stage IIIC. After the first two review rounds, 13 % of cases were classified as "no consensus" and moved to a third round. The main reasons were suboptimal imaging (n = 8), incomplete invasive mediastinal staging to assess the N factor (n = 3), and disagreement on the resectability of T4 tumors invading thoracic structures or with multi-station/bulky N2 disease (n = 3). After the third review round, T3-T4 tumors based on size/satellite nodules and/or with N1-N2 single-station involvement were considered resectable. In contrast, many invasive T4-tumors were considered unresectable, especially if combined with N2-N3 disease. N2-multi-station, N2-bulky or N3 involvement were generally considered unresectable (100 %/95 %/95 % respectively).CONCLUSIONS: After a multiple-round multidisciplinary review of real-world cases, consensus was reached for most TNM-subsets, except for invasive T4N0 tumors. This case review informed the Consensual Definition of Resectable stage III NSCLC in clinical trials.

AB - INTRODUCTION: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease, leading to ambiguity in resectability criteria. This has prompted the EORTC Lung Cancer Group to establish a standardized definition of resectability for clinical trials. A Delphi consensus process was initiated, including a systematic review, survey, and clinical cases review. Here, we report exclusively the results of the clinical cases review, aimed to categorize cases based on tumor and lymph node factors, to identify those deemed surgically resectable upfront.METHODS: Consecutive patients with clinical stage III NSCLC (8th TNM edition) treated at Institut Jules Bordet between 2016-2021 were identified. These cases underwent evaluation by multidisciplinary panels (MDT), comprising thoracic surgeons, radiation oncologists, medical oncologists/pulmonologists and imaging specialists. The MDT determined the resectability of each tumor, and non-consensual cases underwent a second and a third discussion rounds. A TNM-subset was classified as "resectable" if ≥75 % of cases within that category were deemed "resectable" following multiple rounds of review.RESULTS: Among 105 cases, 52 % of tumors were stage IIIA, 36 % stage IIIB and 11 % stage IIIC. After the first two review rounds, 13 % of cases were classified as "no consensus" and moved to a third round. The main reasons were suboptimal imaging (n = 8), incomplete invasive mediastinal staging to assess the N factor (n = 3), and disagreement on the resectability of T4 tumors invading thoracic structures or with multi-station/bulky N2 disease (n = 3). After the third review round, T3-T4 tumors based on size/satellite nodules and/or with N1-N2 single-station involvement were considered resectable. In contrast, many invasive T4-tumors were considered unresectable, especially if combined with N2-N3 disease. N2-multi-station, N2-bulky or N3 involvement were generally considered unresectable (100 %/95 %/95 % respectively).CONCLUSIONS: After a multiple-round multidisciplinary review of real-world cases, consensus was reached for most TNM-subsets, except for invasive T4N0 tumors. This case review informed the Consensual Definition of Resectable stage III NSCLC in clinical trials.

KW - Lung cancer

KW - Real-world

KW - Resectable

KW - Stage III

KW - Surgery

UR - https://www.scopus.com/pages/publications/105018973382

U2 - 10.1016/j.lungcan.2025.108798

DO - 10.1016/j.lungcan.2025.108798

M3 - Journal article

C2 - 41108881

SN - 0169-5002

VL - 209

SP - 108798

JO - Lung Cancer

JF - Lung Cancer

M1 - 108798

ER -

Definition of resectable stage III non-small cell lung cancer (NSCLC) for inclusion in clinical trials: A clinical case review by a pan-European multidisciplinary expert panel led by the EORTC Lung Cancer Group

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