Patient and clinicopathological characteristics.
A total of 1557 patients who underwent PN between 2004 and 2015 were selected from the SEER database. Of these, 904 (57.7%) had left PN and 653 (42.3%) had right PN. The patient characteristics are shown in Table 1. The two groups were similar in age, sex, marital status, race, year of diagnosis, grade, lymph node dissection, tumor stage, T-stage, N-stage, radiotherapy, and chemotherapy, while the primary tumor site and histopathology had a significant difference between sides (P<0.05).
Among all 1557 patients, the mean follow-up was 61.57 ± 10.83 months (61.75 ± 10.62 months, left PN and 61.31 ± 11.12 months, right PN, P=0.432). Median OS was 52 months for left PN vs 33 months for right PN (HR: 0.635; 95% CI 0.552-0.729). One-, 3-, and 5-year overall survival rates for all patients, left PN, and right PN were 76.7%, 53.5%, and 44.7%; 81.4%, 57.5%, and 47.7%; and 70.1%, 48.1% and 40.2%, and OS was significantly worse for right PN (HR: 1.303; 95% CI 1.133-1.498; P<0.001) compared with left PN(Fig. 2a).
We used univariate analysis to identify possible prognostic factors in PN for NSCLC and found statistically significant (P<0.05) correlations between OS and age, sex, summary stage, grade, tumor stage, T-stage, N-stage, radiotherapy, and chemotherapy (Table 2). Chemotherapy was associated with a better prognosis (Fig. 3a) and radiotherapy was associated with a worse prognosis (Fig. 4a). Race, marital status, year of diagnosis, histopathology, primary site, and lymph node dissection were not significant prognostic factors in our univariate analysis (P>0.05). Compared with right PN, left PN had: age ≤50 years (P=0.036), 61-70 years (P=0.001); female (P=0.031), male (P=0.002); white (P<0.001); married (P<0.001); year of diagnosis 2008-2011 (P=0.004), 2012-2015 (P<0.001); single lobe (P=0.035) and overlapping lesion (P=0.001); squamous cell carcinoma (P<0.001); moderately differentiated (P=0.007) and poorly differentiated (P=0.014); regional (P<0.001); number of regional lymph nodes dissected ≥4 (P<0.001); tumor stage II (P=0.001) and III (P=0.026); T2 (P=0.010) and T3 (P=0.004); N0 (P=0.036) and N1 (P<0.001); no radiotherapy (P<0.001) and no/unknown chemotherapy (P<0.001).
Multivariate analysis performed with the Cox regression model included age, sex, summary stage, grade, lymph node dissection, tumor stage, T-stage, N-stage, radiotherapy, and chemotherapy. The results showed that age, sex, grade, lymph node dissection, N-stage, radiotherapy, and chemotherapy were independent predictors of survival time in OS (P<0.05) (Table 2), with radiotherapy appearing as a negative prognostic factor with increased risk of death for OS (HR: 1.264; 95% CI 1.049-1.523; P=0.014) and chemotherapy appearing as an independent predictor of improved for OS (HR: 0.564; 95% CI 0.480-0.661; P<0.001).
Propensity score matching survival analysis
All variables were well balanced between the two groups after 1:1 PSM. The propensity scores before matching were 0.407 ± 0.081 for left PN and 0.436 ± 0.086 for right PN (P<0.001). After matching, the propensity score for both was 0.428 ± 0.082 (P=0.755). Finally, a total of 1230 patients (615 left PN and 615 right PN) were included in our study. We found there were no significant differences in baseline characteristics between matched groups except year of diagnosis (Table 3) (P=0.05). The mean follow-up time was 61.16 ± 10.92 months (61.43 ± 10.89 months, left PN and 61.49 ± 10.95 months, right PN, P=0.927). Median OS was 40 months, left PN, vs 35 months, right PN (HR: 0.875; 95% CI 0.752-1.018). One-, 3-, and 5-year OS rates for all patients were 75.4%, 50.7%, and 41.0%, and between-group OS was not significantly different after matching (HR: 1.061; 95% CI 0.912-1.235; P=0.443) (Fig. 2b).
Subgroup analysis in matched groups
Univariate analysis to identify possible prognostic factors after matching found statistically significant correlations between OS and age, sex, histopathology, summary stage, grade, tumor stage, T-stage, N-stage, radiotherapy, and chemotherapy (P<0.05) (Table 4). The subsequent multivariate Cox regression model showed that age ≥61 (P≤0.002), higher tumor grade (P<0.001), and higher N-stage (P<0.05) were significant independent negative prognostic factors. The multivariate analysis also revealed that chemotherapy was an independent predictor of improved OS (HR: 0.522; 95% CI 0.439-0.621; P<0.001), while radiotherapy remained as a worse prognostic factor with increased risk of death for OS (HR: 1.304; 95% CI 1.063-1.600; P=0.011). The forest plot shows that for all time intervals other than the 2004-2007 period, patients with primary overlapping lung lesions had better OS for left PN vs right PN (HR: 0.684; 95% CI 0.497-0.941; P=0.020). During the 2004-2007 interval, OS for left PN was lower (HR: 0.576; 95% CI 0.346-0.960 P=0.034) (Fig. 5).