Consensus definition of resectable stage III non-small cell lung cancer: A multidisciplinary initiative
Stage III non-small cell lung cancer (NSCLC) is a highly heterogeneous disease. As a consequence, the definition of resectability is not always clear. This initiative establishes a consensus definition of resectable stage III NSCLC for clinical trials. Through extensive multidisciplinary efforts, experts define mandatory diagnostic tests, team composition, and criteria for resectability. This consensus offers guidance for refining treatment strategies and trial designs for stage III NSCLC patients.
Stage III non-small cell lung cancer (NSCLC) is a highly heterogeneous disease. As a consequence, the surgical decision on stage III is highly dependent on the relative expertise of thoracic surgeons and radiation oncologists. The aim of this initiative is to provide a multidisciplinary consensual definition of resectable stage III NSCLC, according to the 8th TNM edition, to be used in clinical trials.
Methods
Three separate work packages were undertaken: 1) a systematic review of the literature since 2007, 2) an international survey investigating current clinical practice and decisions, and 3) multidisciplinary discussions on 105 clinical cases. The final step included a Delphi process, and after multiple rounds of review, a consensus meeting for formalising the definition of resectability took place in Copenhagen in March 2023. This consensus was reached by a group of experts including members and representatives of the EORT Lung Cancer Group.
Results
The consensus meeting agreed that the mandatory work-up to define resectability in stage III NSCLC should include the following exams: contrast-enhanced chest CT scan, 18F FDG PET CT with/without contrast, brain imaging (preferably a brain MRI) and invasive mediastinal/nodal staging (EBUS, EUS, combined EBUS EUS and/or mediastinoscopy). Additional tests may be required if invasion of any neighbouring structures is suspected. Furthermore, it was also agreed that the decision about resectability should be taken by a multidisciplinary team formed by thoracic surgeons, radiation oncologists, medical oncologists and/or pneumo-oncologists, pulmonologists, imaging specialists and pathologists (at least one doctor per speciality). The decision on technical resectability is made by the thoracic surgeon, informed by the multidisciplinary team (MDT).
Subsequently, this meeting aimed to reach a consensus about the resectability of each stage III tumour subgroup. For stage IIIA NSCLC, cT3 N1 tumours are considered resectable independently of the T characteristics: size, multiple nodules in the same lobe or invasion (including chest, ribs). For N2 tumours, pathological confirmation of N2 involvement is mandatory, except for bulky and invasive N2 if the MDT decides that the risk outweighs the benefit, and if pathological confirmation does not influence treatment strategy. Of note, N2 bulky disease was defined as having short node axes (>2.5-3 cm). cT1-2 N2, single-station N2, non-bulky and non-invasive tumours are considered resectable.
For multiple-station N2 tumours, there was no consensus between the results of the systematic review (frequently unresectable) vs. the clinical case review (n=15, all unresectable) vs. the survey (10-40% of the respondents answered that multiple N2 were potentially resectable, depending on the T stage). Consequently, a case-by-case discussion was proposed in which highly and carefully selected patients with non-bulky, non-invasive N2 multi-station involvement may be considered for resection. The exact number of nodes/stations for a tumour to be still considered resectable could not be defined.
For cT1-2 cN2 tumours, there was again no consensual definition of “bulky” between the three parts of the initiative. It was proposed that in specific situations of highly selected patients, the inclusion of those patients in multidisciplinary trials with surgery as local therapy can be discussed. cT4-N0-1 tumours by separate nodules or by size are considered resectable. In contrast, T4 by infiltration of major structures are frequently considered as borderline resectable, and a case-by-case discussion must be performed including an experienced surgeon and frequently a multidisciplinary approach in dedicated specialised centres. In stage IIIB tumours, cT3N2 and cT4 (size or satellite) N2 are considered resectable if they are single-station N2. A case-by-case discussion is recommended for multi-station disease. cT1-2N3 tumours are always considered unresectable. Finally, in the stage IIIC setting, cT3-4 N3 tumours are considered unresectable.
Conclusion
This study included recommendations related to the appropriate initial workup for assessing resectability, the composition of the team required to make the decision on resectability, and the consensus of resectability for different types of tumours. Most N3, N2 invasive and N2 bulky tumours are considered unresectable. On the other hand, T1-2, T3, T4 tumours with no or limited node lymph involved are considered resectable. Finally, small tumours with N2 bulky disease and N2 multi-station disease are potentially resectable. These cases should be discussed in an MDT, and their inclusion in trials with surgery as treatment can be considered. Some T4 tumours by infiltration are potentially resectable.
Reference
Brandao M, et al. Consensual Definition of Stage III NSCLC Resectability: EORTC-Lung Cancer Group Initiative with Other Scientific Societies. Presented at WCLC 2023; Abstract OA06.05.
