Letter to the Editor: Clinical Implications of Postoperative Radiotherapy on Patient Survival in Stage IIIA Resected Lung Cancer: More Variables Should Be Considered

Re: Gao F, Li N, Xu Y, et al. Effects of postoperative radiotherapy on survival of patients with stage IIIA resected non–small cell lung cancer: analysis of the SEER database. J Natl Compr Canc Netw 2020;18(6):718–727.

We would like to comment on the recent article by Gao et al,¹ titled “Effects of Postoperative Radiotherapy on Survival of Patients With Stage IIIA Resected Non–Small Cell Lung Cancer: Analysis of the SEER Database.” The authors found that postoperative radiotherapy (PORT) significantly improved overall survival and decreased lung cancer–related mortality in patients with stage IIIA, N2 disease with ≥6 positive lymph node metastases. The authors should be commended on their efforts to address an important question in thoracic oncology. However, we have some concerns.

First, as shown in Tables 1 and 2, the authors listed the information on postoperative chemotherapy, which was a significant parameter in patients with stage IIIA non–small cell lung cancer (NSCLC). However, the sequence of radiotherapy and surgery could be obtained in the SEER database, but the sequence and details of chemotherapy regimens was not provided.^2,3 How could the authors ensure that the chemotherapy was not given before surgery given that neoadjuvant chemotherapy might be administered to patients with suspected stage IIIA-N2 disease?

Second, given that the authors provided the number of positive lymph nodes in the tables, why was the total number of harvested nodes, which possibly affected decisions regarding PORT, not available? More specifically, patients with a lower lymph node yield along with metastatic mediastinal lymph nodes were more likely to receive PORT to improve local control. Meanwhile, it has been reported that a greater lymph node yield was associated with a greater number of positive lymph nodes and could correlate with a lower probability of stage migration.⁴ Therefore, the data on examined lymph nodes in each cohort are important and should have been displayed.

Finally, the SEER database is not an ideal tool for assessing the role of PORT in resected NSCLC because it does not include information on surgical margin. As shown in Figure 2, is it inspiring to show patients with resected N0 and N1 disease undergoing PORT who have worse survival compared with those undergoing non-PORT? A major source of potential bias is that surgeons and radiation therapists might have identified adverse prognostic factors during or after surgery, which led to referring patients for radiation therapy consultation. An important prognosticator is the quality of surgical resection, including surgical margin status and adequacy of nodal staging. Therefore, R1/R2 resection and inadequate lymph node sampling probably accounted for the significantly poorer survival in patients with N0/N1 disease receiving PORT. These points should be addressed before the results can be interpreted into clinical practice.