Accurate prediction of survival prognosis is critical for better management of NSCLC patients, and to date, this mainly relied on the AJCC TNM staging system. However, the predictive performance of the existing systems for NSCLC remains unsatisfactory[13]. In fact, even in patients with the same TNM stage, the survival outcomes remain heterogenous[14]. In this study, for the first time, a novel nomogram with lymph node status was established and validated for predicting overall survival outcomes in IIIA-N2 NSCLC patients, which is user-friendly, accurate, and practical.
Various studies had reported several variables associated with the prognosis of patients with lung cancer. Li et al found that T stage, N stage, the number of examined lymph nodes and age were statistically prognostic factors for surgical resected carcinoma of the lung[15]. In the present study, the prognostic values of the lymph node status in IIIA-N2 NSCLC patients receiving curative surgery were investigated. The X-tile software was utilized to explore the optimal cutoff points of ELN, MLN, and LNR. The combination of ELN, MLN, and MLNR could effectively reflect the involvement of regional metastasis and the extent of surgery, and the result of univariate analysis confirmed that these variables were prognostic predictors for IIIA-N2 NSCLC patients.
Notably, only variables of lymph node status are not sufficient to accurately reflect the postoperative prognosis of IIIA-N2 NSCLC patients. In the present study, all variables of interest were included into the multivariate analysis, and seven clinicopathologic features were finally identified as independent prognostic factors, including age, sex, T stage, pathologic grade, ELN, MLN, and LNR. Among all these variables, LNR > 0.45 made the greatest contribution to poorer prognosis followed by undifferentiated grade and MLN > 6. C-index and calibration curves indicated that the predictive performance of the nomogram was satisfactory.
The goal of systemic therapy in NSCLC patients is to mitigate symptom burden from NSCLC and improve survival outcomes, with a co-occurrent aim of improving the quality of life[16]. Whether adjuvant radiotherapy is suitable for NSCLC patients was kept controversial for decades, especially since the results reported by PORT Meta-analysis Trialists Group in 1998[17]. Some previous studies reported that PORT could not prolong the survival rate of NSCLC patients compared with surgery alone[18]. In the meantime, some studies revealed that with the progress of radiotherapy technology, PORT could significantly improve the prognosis of IIIA-N2 NSCLC patients, resulting in reduced local-regional recurrence and better OS[19]. Notably, even in IIIA-N2 NSCLC patients, the survival outcomes are heterogeneous, and not all IIIA-N2 NSCLC patients could benefit from the treatment of radiation. The role of PORT in prolonging overall survival should be further investigated in NSCLC patients, especially in those with IIIA-N2 NSCLC.
Personal clinicopathologic features should be considered carefully when making a therapeutic decision for each patient. And it is critical to integrate these factors to identify IIIA-N2 NSCLC patients who can benefit from PORT. Based on the survival-predicting model, we proposed a novel risk stratification system and the survival benefits of PORT were analyzed in each risk subgroup. The results showed that POCT was recommended for all patients with IIIA-N2 NSCLC. Additionally, only patients in high-risk group, instead of those in low-risk and moderate-risk groups, could benefit prognostically benefit from the combination of PORT and POCT, which provided more valuable information for therapeutic decision-making.
To the best of our knowledge, this is the first comprehensive attempt to develop a population-based nomogram that predicts the prognosis of IIIA-N2 NSCLC patients after surgery. Our survival-predicting nomogram can be practically applied to the clinical works to predict the prognosis of IIIA-N2 NSCLC patients and facilitate clinical consultation, which is able to help to make therapeutic plans ahead on follow-up and surveillance. Furthermore, we proposed a novel patient classification strategy, which could assess the survival benefit of PORT for each patient.
There are still several limitations in the present study which should be highlighted, including its retrospective nature and potential selection biases[20]. Furthermore, information about some potential prognostic factors, such as the detailed chemotherapy protocol, molecular or genomic data, were not available in this database. Accordingly, we failed to incorporate these parameters into our model. Future studies are warranted to improve this model by incorporating more valuable prognostic features. In addition, the majority of patients enrolled in this study were Caucasian and black, so this nomogram is expected to externally validated, especially in the Asian population. Last, the recent development of immune checkpoint inhibitors (ICIs) has profoundly changed the treatment strategy of patients with IIIA-N2 NSCLC, but our study failed to reveal the survival benefits of ICIs on these patients. Nevertheless, we agree with the viewpoint of the SEER database that despite the limitations in the population-based analysis, “big data” will definitely continue to be an indispensable part of medical studies for the purpose of hypothesis-generating exploratory analyses[21].
In conclusion, a novel survival-predicting nomogram and risk stratification system were established for predicting individual OS in IIIA-N2 NSCLC. This study may help physicians in making therapeutic decisions and contribute to the design of future prospective researches.