Real-world outcomes of uncertain resection in surgically resected pN2 Non-Small Cell Lung Cancer

In addition to the standard R classification for assessing radicality in Non-Small Cell Lung Cancer (NSCLC), the concept of uncertain resection [R (un)] has been introduced. This study aimed to evaluate the prognostic impact of R (un) in a cohort of surgically resected pN2 NSCLC patients and to analyze outcome of a possible change in the R (un) description.

We retrospectively analyzed data from prospective databases of four institutions. All consecutive patients with R0 pN2 NSCLC treated between 2016 and 2021 were included. Each case was re-evaluated and classified as either R0 or R (un). We also assessed a modified R (un) classification considering station 7 as hierarchically superior to stations 5 and 6.

Among 230 patients, 98 (42.6 %) were female. Forty-six patients (20 %) received neoadjuvant therapy, and 178 (77.4 %) underwent lobectomy. Single station pN2 was observed in 143 patients (62.2 %), and 130 (56.5 %) were reclassified as R (un). Adjuvant therapy was administered to 135 patients (58.7 %). Patients classified as R0 had significantly better overall survival (OS, p = 0.044) and disease-free survival (DFS, p = 0.050) compared to those with R (un). However, in multivariable analysis, only adjuvant therapy remained an independent prognostic factor for OS. When applying the modified R (un) definition, R (un) remained associated with worse OS (p = 0.007) and DFS (p < 0.001) and was confirmed as an independent prognostic factor in multivariable analysis.

Our findings confirm the prognostic relevance of the R classification, including R (un). We propose a possible refinement of the R (un) definition potentially improving its prognostic accuracy.