Risk factors and a prognostic model for patients with borderline resectable locally advanced T3-4N0-1 non-small cell lung cancer: a population-based study

Abstract

Background: Non-small cell lung cancer (NSCLC) is a malignant disease with a significant morbidity rate. For patients diagnosed with borderline resectable locally advanced (T3-4 invasion and N0-1) NSCLC, the optimal treatment and prognosis are still under debate. This study aimed to develop a predictive nomogram that could assess the prognosis of these patients and optimize clinical decision-making.

Methods: Between 2010 to 2015, the survival, demographic and clinical characteristics of patients with borderline resectable locally advanced T3-4N0-1 NSCLC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazard regression analyses were conducted to identify potential factors, which were further utilized to develop a dynamic nomogram for personalized prediction. Internal and external validation were conducted to verify the predictive accuracy of the nomogram.

Results: Totally, 5,054 eligible records were enrolled into the study cohort. The included patients were divided into a training cohort (n=3,538) and a validation cohort (n=1,516) in a 7:3 ratio. Nine independent prognostic factors (including age, gender, primary site, lymph node removal, differentiation grade, T stage, N stage, histology and adjuvant chemotherapy) were finally included into the nomogram. The developed nomogram exhibited favorable discriminative ability with the C-index =0.71. Moreover, the calibration curves demonstrated excellent agreement between predicted and observed outcomes in both the training and validation cohorts. Notably, subgroup analyses revealed that neoadjuvant chemotherapy was significantly associated with a better overall survival (OS) (P<0.05) in patients staged as T3-4N1.

Conclusions: In this study, we developed and validated a prognostic model to assist in clinical decision-making for patients with borderline resectable locally advanced T3-4N0-1 NSCLC. Our findings suggested that patients with T3-4N1 stage disease may derive significant benefits from neoadjuvant chemotherapy.

Keywords: Borderline resectable locally advanced non-small cell lung cancer (borderline resectable locally advanced NSCLC); neoadjuvant chemotherapy; prognosis.

Figure 1

Flow chart of the study design. NSCLC, non-small cell lung cancer; ROC, the receiver operating characteristic.

Figure 2

Forest plot of predicted model for patients with T3–4 invasion N0–1 resectable NSCLC. *, 0.01≤P<0.05; **, 0.001≤P<0.01; ***, P<0.001. OR, odds ratio; CI, confidence interval; LL, left lower lobe; RL, right lower lobe; LU, left upper lobe; RM, right middle lobe; RU, right upper lobe; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; LN, lymph node; T, tumor; N, node; NSCLC, non-small cell lung cancer.

Figure 3

Prognostic nomogram for patients with T3–4 invasion N0–1 resectable NSCLC. LU, left upper lobe; RM, right middle lobe; RU, right upper lobe; LL, left lower lobe; RL, right lower lobe; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; LN, lymph node; T, tumor; N, node; NSCLC, non-small cell lung cancer.

Figure 4

The prognostic nomogram was validated using ROC curve and calibration curves. The ROC curve demonstrated the discrimination ability of the nomogram in both the training cohort (A) and validation cohort (B). In the training cohort, the AUC values for 1-, 3-, and 5-year survival were 0.71, 0.67, and 0.66, respectively. Similarly, in the validation cohort, the AUC values for 1-, 3-, and 5-year survival were 0.67, 0.65, and 0.66, respectively. The calibration curves demonstrated the calibration of the nomogram in both the training cohort (C) and validation cohort (D). AUC, the area under the ROC curve; ROC, receiver operating characteristic; OS overall survival.

Figure 5

Survival analyses for patients diagnosed with T3–4 invasion N0–1 resectable NSCLC. Total Kaplan-Meier curves for the training cohort (P<0.001) (A) and the validation cohort (P<0.001) (B). Subgroup analyses demonstrated that patients diagnosed with T3–4N1 resectable NSCLC could benefit from neoadjuvant therapy, as shown in the training cohort (P=0.044) (C) and the validation cohort (P=0.042) (D). However, patients with T3–4N0 resectable NSCLC did not benefit from neoadjuvant therapy, as indicated in the training cohort (P=0.096) (E) and the validation cohort (P=0.74) (F). NSCLC, non-small cell lung cancer.