ALK rearrangement is detected in 2–5% of NSCLC patients . Crizotinib, an ALK–TKI, has shown clinical efficacy in the treatment of NSCLC with ALK rearrangement . However, most patients develop resistance to crizotinib within 1 year of therapy. Second-generation ALK inhibitors such as alectinib and brigatinib have been developed to overcome resistance to crizotinib. Treatment with these second-generation ALK inhibitors has been well tolerated and has shown efficacy in crizotinib-resistant lung cancers with ALK rearrangement . These ALK inhibitors can also be used as first-line treatment for NSCLC with ALK rearrangement .
Lorlatinib, a third-generation ALK inhibitor, has the broadest coverage of ALK resistance mutations that have been identified. It has been a standard treatment option for ALK-positive patients who have experienced failure of one or more ALK inhibitors .
Although the mechanisms of acquired resistance to initial ALK–TKIs have been elucidated, treatment methods after failure of initial ALK–TKI therapy remain controversial. Some of the treatment options after initial ALK–TKI treatment failure include ALK sequential therapy (switching to lorlatinib or brigatinib) and cytotoxic chemotherapy with or without immune checkpoint inhibitors.
Salvage surgery has been recognized as a surgical treatment for patients with residual tumors or recurring tumors even after definitive chemotherapy and/or radiation therapy.
Shimizu et al.  reported that salvage surgery for NSCLC patients after chemoradiotherapy and conventional radiotherapy can cause minimal complications and reasonable outcomes in selected patients. Their patients’ 3-year overall survival (OS) is 67.3%, and the overall 30- and 90-day mortality are 0 and 0.9%, respectively . Although salvage surgery is a feasible therapeutic modality for advanced NSCLC, its survival benefits remain unclear. To date, some salvage surgery trials have been attempted. Ohtaki et al.  reported that salvage surgery after TKI treatment may be beneficial for NSCLC patients. They included 36 patients who underwent TKI treatment followed by salvage surgery . They obtained grade 3 adverse events, 3 year OS, and 90 day mortality of 5.6, 75.1, and 0%, respectively. However, many of these patients’ driver gene alterations were EGFR mutations. Only three patients had ALK rearrangement.
We have done research on PubMed and also looked up on the internet using lung cancer, ALK, and salvage surgery as key words. Several reports have also described salvage surgery for initially unresectable NSCLC treated with ALK–TKIs [8, 9]. To the best of our knowledge, this report is the first to indicate that salvage surgery after first-line ALK–TKI treatment and subsequent switching to second-line ALK–TKI is effective in a patient with ALK-rearranged locally advanced pleomorphic carcinoma of the lungs. Our patient was first treated with alectinib for 6 months. The lung tumor regrew, while the metastatic lymph nodes exhibited remarkable improvement. The therapeutic response showed a dissociation between the main lung tumor and the metastatic lymph nodes. Salvage surgery was planned, and left upper lobectomy with mediastinal lymph node dissection was performed. Subsequently, second-line ALK–TKI lorlatinib was administered for 8 months, and no evidence of recurrence was found 22 months after salvage surgery. Ohtaki et al.  showed the possible benefits of salvage surgery after TKI treatment; however, recurrence-free survival after surgery was only 22%. Such findings suggested that initially unresectable mutation-positive NSCLCs were still systemic diseases even after salvage surgery and postoperative systemic therapy was important for managing the patients. Some postoperative treatment options include restarting initial TKI treatment, using other TKIs, and administering cytotoxic chemotherapy. In our case, lorlatinib was selected as postoperative therapy because of its efficacy after failure of a first-line, second-generation ALK–TKI.
Our case suggested that salvage surgery after first-line ALK–TKI treatment followed by second-line ALK–TKI provides a favorable clinical benefit to the treatment of patients with ALK-rearranged locally advanced NSCLC.