Patient characteristics

The clinical and pathological characteristics of the included patients are summarized in Table 1. The median age was 66.0 years (IQR: 58.0 to 72.0 years). The most frequently performed surgery was lobectomy (n = 3553, 88.2%) and the median number of harvested lymph node was 17.0 (IQR: 11.0 to 24.0). Adenocarcinoma (n = 3017, 74.9%) was the most common histologic cell type, and 1225 patients (30.4%) received adjuvant chemotherapy. The median follow-up period was 6.1 years (IQR: 4.0 to 9.7 years). The TNM staging classification was categorized according to the 8th and proposed 9th editions and summarized in Fig. 1. The patients classified as N2 in the 8th edition were further divided into N2a (256 patients, 72.7%) and N2b (96 patients, 27.3%) according to the proposed 9th edition (Fig. 1A). Some patients experienced changes in TNM staging when the 9th edition was used, as follows: 151 patients (26.0%) were down-staged from stage IIB to IIA, 56 patients (12.4%) were up-staged from IIIA to IIIB, 52 patients (11.5%) were down-staged from IIIA to IIB, and 57 patients (61.3%) were down-staged from IIIB to IIIA (Fig. 1B).

Table 1 Clinical and pathological characteristics of included patients (N = 4029)Fig. 1

Cross table plots of 8th and proposed 9th edition TNM staging classification (A) and N staging classification (B)

Survival analyses according to the 8th and proposed 9th editions of the TNM staging classifications

In Fig. 2, we present the OS and FFR for bothdkdn the 8th and proposed 9th editions of the TNM staging classification. In the 8th edition, the survival curves of OS and FFR demonstrated a stepwise decline from stage IA to IIIB. However, the OS curves of stage IIA and IIB and the FFR curves of stage IB and IIA were not significantly different (P = 0.227 and P = 0.607, respectively). According to the proposed 9th edition, the survival curves of OS and FFR also displayed a stepwise degradation, and there were clearer differences in the OS curves of stage IIA and IIB (P = 0.026) and FFR curves of stage IB and IIA (P = 0.253). The exploratory analysis compared survival outcomes between segmentectomy and lobectomy in patients with pathologic stage IA (Fig. 3). The 5-year OS and FFR were 95.3% (95% CI, 92.5–98.3%) and 95.6% (95% CI, 93.2–98.2%) in the segmentectomy group, which showed comparable outcomes to the lobectomy group (5-year OS, 92.9% [95% CI, 91.6–94.2%], P = 0.172; 5-year FFR, 94.6% [95% CI, 92.8–95.2%], P = 0.760).

Fig. 2

Survival curves of overall survival (A) and freedom-from recurrence (B) based on the 8th and proposed 9th edition of the TNM staging classification

Fig. 3

Survival curves of overall survival (A) and freedom-from recurrence (B) between the segmentectomy and the lobectomy group in patients diagnosed with pathologic stage IA

The multivariable Cox regression analysis consistently revealed HR values above 1.0 when comparing adjacent stages for both OS and FFR (Table 2). However, a significant difference was not observed between stages IB and IIA in both editions for OS and FFR (8th edition, P = 0.224 for OS, P = 0.601 for FFR; proposed 9th edition, P = 0.056 for OS, P = 0.358 for FFR). The AIC, R [2], and C-index demonstrated the superiority of the proposed 9th edition of TNM staging classification compared to the 8th edition, with a lower AIC value (OS: 13670 vs. 13660, FFR: 11904 vs.11878), a higher R [2] value (OS: 0.603 vs. 0.608, FFR: 0.590 vs. 0.603), and a higher C-index (OS: 0.778 vs. 0.779, FFR: 0.765 vs. 0.769).

Table 2 Multivariable Cox proportional hazard model for 8th and proposed 9th TNM staging classificationSurvival analyses according to the 8th and proposed 9th N staging classifications

Figure 4A shows sequential deteriorations in OS in both the 8th and proposed 9th editions of the N stage. According to the proposed 9th edition, the OS curves between the N1 group and N2a group were not significantly different (P = 0.203). However, according to multivariable Cox proportional hazard analysis, all HRs between adjacent N staging groups were higher than 1.0, indicating a gradual decline in the prognosis according to the proposed N staging groups (Fig. 3A). The AIC, R [2], and C-index values consistently demonstrated better prediction accuracy and discriminatory ability for the proposed 9th edition than for the 8th edition (AIC: 13763 vs. 13772, R [2]: 0.561 vs. 0.555, C-index: 0.762 vs. 0.761).

Fig. 4

Survival curves of overall survival (A) and freedom-from recurrence (B) based on the 8th and proposed 9th edition of the N staging classification

When applying the 9th edition N staging groups for FFR, the differences across groups were very clear (Fig. 4B). The AIC, R [2], and C-index values consistently demonstrated better prediction accuracy and discriminatory ability for the proposed 9th edition than for the 8th edition (AIC: 12081 vs. 12096, R [2]: 0.483 vs. 0.471, C-index: 0.735 vs. 0.734).

Exploratory analyses according to the subdivision of the N2a group into N2a1 and N2a2

We conducted an exploratory analysis according to skip N2 metastasis, which was proposed in the 8th edition but not applied in the 9th edition (Fig. 5). Depending on whether N1 skip metastasis was present, the N2a group (n = 256) was divided into N2a1 (n = 101) and N2a2 (n = 155) groups. There was a significant stepwise worsening of the FFR curves, except for N1 and N2a1 (P = 0.989). After grouping N1 and N2a1 into the same category (N1 + N2a1 group), multivariable Cox regression analysis revealed significant HRs between the adjacent groups, with all HR values exceeding 1.0. Using the proposed 9th edition as a reference, AIC, R [2], and C-index values indicated better results after inclusion of skip N2 metastasis (AIC: 12077 vs. 12081, R [2]: 0.485 vs. 0.483, C-index: 0.736 vs. 0.735). However, the gradual increase in recurrence according to skip N2 metastasis was not significantly associated with poorer survival outcomes, indicating some overlapping of the OS curves between N1 and N2a1 (P = 0.196), N2a1 and N2a2 (P = 0.660), and N2a2 and N2b (P = 0.136).

Fig. 5

Survival curves of freedom-from recurrence (A) and overall survival (B) according to subdivision of N2a group as N2a1 and N2a2