Absent preoperative non-small cell lung cancer confirmation and relevant stage migration in the era before neoadjuvant chemoimmunotherapy: implications for treatment decisions in resectable non-small cell lung cancer

Guus R M van den Heuvel; Bas L R Mandos; Olga C J Schuurbiers; Francesco Ciompi; Erik Aarntzen; Kaamar Azijli; Iris Walraven; Hans J M Smit; Michel M van den Heuvel

doi:10.21037/tlcr-2024-1120

Absent preoperative non-small cell lung cancer confirmation and relevant stage migration in the era before neoadjuvant chemoimmunotherapy: implications for treatment decisions in resectable non-small cell lung cancer

Transl Lung Cancer Res. 2025 May 30;14(5):1543-1557. doi: 10.21037/tlcr-2024-1120. Epub 2025 May 22.

Authors

Guus R M van den Heuvel¹, Bas L R Mandos¹, Olga C J Schuurbiers¹, Francesco Ciompi², Erik Aarntzen³, Kaamar Azijli⁴, Iris Walraven⁵, Hans J M Smit⁶, Michel M van den Heuvel¹

Affiliations

¹ Department of Pulmonology, Radboud University Medical Center, Nijmegen, the Netherlands.
² Department of Computational Pathology, Radboud University Medical Center, Nijmegen, the Netherlands.
³ Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
⁴ Department of Medical Affairs, Merck Sharp & Dohme B.V., Haarlem, the Netherlands.
⁵ Department of IQ Health, Radboud University Medical Center, Nijmegen, the Netherlands.
⁶ Department of Pulmonology, Rijnstate Hospital, Arnhem, the Netherlands.

Abstract

Background: Achieving preoperative pathological confirmation and accurate clinical staging are crucial for neoadjuvant treatment decisions in resectable non-small cell lung cancer (NSCLC), though often challenging. This study examines the prevalence of missing preoperative pathological confirmation with focus on patients with clinical stage II or III NSCLC. In addition, pre- and postoperative staging discrepancies are studied in the presence of preoperative NSCLC confirmation. These two impeding factors were studied in an era before the introduction of neoadjuvant chemoimmunotherapy in resectable NSCLC.

Methods: In this retrospective observational study, patients with resectable NSCLC diagnosed between 2015 and 2019 were selected. The prevalence of absent preoperative confirmation of NSCLC was evaluated. Stage migration was analyzed in the overall population and across two patient cohorts with either a present or absent upfront pathological NSCLC diagnosis. Relevant stage migration was assessed in the cohort with preoperative NSCLC confirmation. Relevant upstaging was defined as migration from clinical stage I to pathological stage IIA-IIIB and relevant downstaging from clinical stage IIA-IIIB to pathological stage I.

Results: In 277 of 809 patients (34.2%), no preoperative pathological NSCLC diagnosis was obtained, including 83 patients with clinical stage II or III disease (30.0% and 10.3% of the total cohort). In 532 of 809 patients (65.8%), preoperative pathological NSCLC confirmation was achieved. In this cohort, relevant stage migration was noticed in 105 patients (19.7% and 13.0% of the total cohort).

Conclusions: In the era before the introduction of neoadjuvant chemoimmunotherapy as standard of care, absent preoperative NSCLC confirmation or inaccurate staging occurred in nearly a quarter of potential candidates for neoadjuvant treatment. These two limiting factors will need to be addressed in order to adequately administer neoadjuvant therapy in patients with resectable NSCLC conform current guidelines.

Keywords: Non-small cell lung cancer (NSCLC); cancer diagnostics; stage migration; treatment decision-making.