Postoperative radiotherapy enhances survival in NSCLC patients with moderate lymph node metastases following surgery: A SEER-based population cohort study

Abstract

The role of postoperative radiotherapy (PORT) for non-small cell lung cancer (NSCLC) is still debated. A nonlinear relationship may exist between the number of positive lymph nodes (PLN) and the benefits of PORT. Our study seeks to identify patient subgroups that could benefit from PORT by stratifying them based on PLN counts. We enrolled patients with pathologic N2 NSCLC who underwent surgery and adjuvant chemotherapy between January 2004 and December 2015 from the surveillance, epidemiology, and end results (SEER) database. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared between patients receiving PORT and those not receiving PORT. The restricted cubic spline analysis model was applied to investigate the relationship between PLNs and survival. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was applied to compare survival outcomes between the PORT and non-PORT groups. Cox proportional hazard models were employed to calculate adjusted hazard ratios and their corresponding 95% confidence intervals. A total of 4048 patients were eligible, with a median follow-up time of 103 months. PORT had a negative impact on OS (HR = 1.08, 95% CI = 1.01-1.17, P = .03) and showed no association with LCSS (HR = 1.06, 95% CI = 0.98-1.15, P = .14). The restricted cubic spline analysis analysis indicated that PLN counts could modify the effects of PORT on survival. Patients were categorized into 3 risk subgroups according to their PLN counts: low-risk (1-4 PLNs), moderate-risk (5-6 PLNs), and high-risk (over 6 PLNs). In the low-risk subgroup, PORT exhibited an adverse effect on OS (HR = 1.17, 95% CI = 1.00-1.28, P < .01). Conversely, in the moderate-risk subgroup, PORT improved OS (HR = 0.72, 95% CI = 0.60-0.87, P < .01). In the high-risk subgroup, PORT had no impact on OS (HR = 1.00, 95% CI = 0.86-1.16, P = 1.00). Analysis in LCSS showed consistent results. While PORT does not universally improve survival outcomes for all patients with pN2 NSCLC, it improves survival for those with a moderate number of PLNs.

Keywords: SEER; lymph node metastases; non-small cell lung cancer; radiation therapy; surgery; survival.

Figure 1.

Postoperative radiotherapy negatively impacted overall survival (A) and was not associated with lung cancer-specific survival (B) in the whole cohort.

Figure 2.

The restricted cubic spline analysis revealed the effects of PLNs on survival in the non-PORT (A) and PORT (B) groups. The horizontal dashed blue line indicates the reference hazard ratio (HR = 1), and the vertical dashed red line denotes the reference point at 6 PLNs, which was used as the reference value in the spline model. HR = hazard ratio, PLN = positive lymph node, PORT = postoperative radiotherapy.

Figure 3.

The impact of PORT on OS, stratified according to the number of PLNs. OS = overall survival, PLN = positive lymph node, PORT = postoperative radiotherapy.

Figure 4.

The impact of PORT on LCSS, stratified according to the number of PLNs. LCSS = lung cancer-specific survival, PLN = positive lymph node, PORT = postoperative radiotherapy.

Figure 5.

Postoperative radiotherapy led to a decrease in OS in the low-risk subgroup (A). PORT provided an OS benefit in the moderate-risk subgroup (B). PORT did not improve OS in the high-risk subgroup (C). OS = overall survival, PORT = postoperative radiotherapy.

Figure 6.

Postoperative radiotherapy decreased LCSS in the low-risk subgroup (A). PORT provided an LCSS benefit in the moderate-risk subgroup (B). PORT did not improve LCSS in the high-risk subgroup (C). LCSS = lung cancer-specific survival, PORT = postoperative radiotherapy.