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Review
. 2023 Jul 3;15(13):3475.
doi: 10.3390/cancers15133475.

True Prevalence of Unforeseen N2 Disease in NSCLC: A Systematic Review + Meta-Analysis

Wing Kea Hui  1 , Zohra Charaf  2 , Jeroen M H Hendriks  1   3 , Paul E Van Schil  1   3
Affiliations
Review

True Prevalence of Unforeseen N2 Disease in NSCLC: A Systematic Review + Meta-Analysis

Wing Kea Hui et al. Cancers (Basel). .

Abstract

Patients with unforeseen N2 (uN2) disease are traditionally considered to have an unfavorable prognosis. As preoperative and intraoperative mediastinal staging improved over time, the prevalence of uN2 changed. In this review, the current evidence on uN2 disease and its prevalence will be evaluated. A systematic literature search was performed to identify all studies or completed, published trials that included uN2 disease until 6 April 2023, without language restrictions. The Newcastle-Ottawa Scale (NOS) was used to score the included papers. A total of 512 articles were initially identified, of which a total of 22 studies met the predefined inclusion criteria. Despite adequate mediastinal staging, the pooled prevalence of true unforeseen pN2 (9387 patients) was 7.97% (95% CI 6.67-9.27%), with a pooled OS after five years (892 patients) of 44% (95% CI 31-58%). Substantial heterogeneity regarding the characteristics of uN2 disease limited our meta-analysis considerably. However, it seems patients with uN2 disease represent a subcategory with a similar prognosis to stage IIb if complete surgical resection can be achieved, and the contribution of adjuvant therapy is to be further explored.

Keywords: nodal disease; non-small cell lung cancer; surgery.

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Conflict of interest statement

Authors J.H., W.K.H. and Z.C. declare no conflict of interest. Author P.V.S. is on the advisory board and/or receives honoraria for lectures from AstraZeneca, BMS, Roche, MSD and Janssen and is president-elect IASLC (International Association for the Study of Lung Cancer) and treasurer BACTS (Belgian Association for Cardiothoracic Surgery).

Figures

Figure A1
Figure A1
Forest plot of pooled prevalence of uN2N disease, stratified according to study period.
Figure A2
Figure A2
Forest plot of pooled prevalence of uN2 disease, stratified according to invasive mediastinal staging.
Figure A3
Figure A3
Forest plot of pooled prevalence of uN2 disease, stratified according to type of intraoperative lymph node assessment.
Figure A4
Figure A4
Forest plot of pooled prevalence of uN2 disease, stratified according to type of surgery.
Figure A5
Figure A5
Forest plot of three-year overall survival of patients with uN2 disease and complete resection.
Figure A6
Figure A6
Forest plot of ten-year overall survival of patients with uN2 disease and complete resection.
Figure A7
Figure A7
Forest plot of five-year overall survival of patients with uN2 disease and complete resection, according to region.
Figure 1
Figure 1
Revised ESTS guidelines for primary mediastinal staging (2014) [2].
Figure 2
Figure 2
Study flow diagram according to PRISMA guidelines 2020 [7].
Figure 3
Figure 3
Pooled prevalence of uN2 disease + risk of bias assessment.
Figure 4
Figure 4
Funnel plot of pooled prevalence of the uN2 disease.
Figure 5
Figure 5
Forest plot of five-year overall survival of patients with uN2 disease and complete resection.
Figure 6
Figure 6
Forest plot of three-year disease-free survival of patients with uN2 disease and complete resection.
Figure 7
Figure 7
Forest plot of five-year disease-free survival of patients with uN2 disease and complete resection.
See this image and copyright information in PMC

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