[Long-term survival of personalized surgical treatment of locally advanced non-small cell lung cancer based on molecular staging].

BACKGROUND AND OBJECTIVE: Approximately 35%-40% of patients with newly diagnosed non-small cell Lung cancer have locally advanced disease. The average survival time of these patients only have 6-8 months with chemotherapy. The aim of this study is to explore and summarize the probability of detection of micrometastasis in peripheral blood for molecular staging, and for selection of indication of surgical treatment, and beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in locally advanced lung cancer; to summarize the long-time survival result of personalized surgical treatment of 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods.

METHODS: CK19 mRNA expression of peripheral blood samples was detected in 516 lung cancer patients by RT-PCR before operation for molecular diagnosis of micrometastasis, personalized molecular staging, and for selection of indication of surgical treatment and the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in patients with locally advanced nonsmall cell lung cancer invaded heart, great vessels or both. The long-term survival result of personalized surgical treatment was retrospectively analyzed in 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods.

RESULTS: There were 322 patients with squamous cell carcinoma and 194 cases with adenocarcinoma in the series of 516 patients with locally advanced lung cancer involved heart, great vessels or both. There were 112 patients with IIIA disease and 404 cases with IIIB disease according to P-TNM staging. There were 97 patients with M-IIIA disease, 278 cases with M-IIIB disease and 141 cases with III disease according to our personalized molecular staging. Of the 516 patients, bronchoplastic procedures and pulmonary artery reconstruction was carried out in 256 cases; lobectomy combined with resection and reconstruction of partial left atrium was performed in 41 cases; Double sleeve lobectomy combined with resection and reconstruction of super vena cava was carried out in 90 cases; Lobectomy combined with resection and reconstruction of diaphragm was performed in 3 cases; Double sleeve lobectomy combined with resection and reconstruction of partial left atrium was performed in 30 cases; Bronchoplastic procedures and pulmonary artery reconstruction combined with reconstruction of aorta sheath was carried out in 10 cases; Right pneumonectomy combined with resection and reconstruction partial left atrium, total right diaphragm with Dacron, and post cava and right liver vein was performed in one case; Lobectomy combined with resection and reconstruction of carina was carried out in 10 cases; Bronchoplastic procedures and pulmonary artery reconstruction combined with resection and reconstruction of carina and superior vane cava, or combined with superior vena cava and left atrium, or with carina and left atrium was performed in 55 cases in this series. Five patients died of operative complications and the operative mortality was 0.97%. CK19 mRNA expression was found in 141 patients. The positive rate of CK19 mRNA expression was 27.3% in peripheral blood samples in the 516 cases. The positive rates of micrometastasis in peripheral blood was significantly related to histological classification, P-TNM staging and N staging of the cancer (P < 0.05), but not to age, sex, smoking status of the patients, and size of primary tumor, and locations of the tumor (P > 0.05). The median survival time was 43.74 months. The 1, 3, 5 and 10 year survival rates of the 516 cases was 89.1%, 39.3%, 19.8% and 10.4%, respectively. The postoperative survival rate was remarkably correlated with micrometastasis in peripheral blood, histological classification of the tumor, size of primary cancer and lymph mode involvement (P < 0.05). The results of multivariable Cox model analysis showed that "personalized molecular P-TNM staging", micrometastasis in peripheral blood, pathological types of the tumor and mediastinal lymph node metastasis of the cancer were the most significant factors for predicting prognosis in the patients with locally advanced nonsmall lung cancer.

CONCLUSIONS: (1) Micrometastasis was existed in peripheral blood of patients with lung cancer, which can not be detected with conventional methods. (2) Detecting of CK19 mRNA expression in peripheral blood in lung cancer patients can be used for diagnosis of micrometastasis of lung cancer and "molecular staging" and "molecular P-TNM staging" for lung cancer patients. It will be helpful for selection of surgical treatment indication, the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in the patients with locally advanced non-small cell lung cancer. (3) Personalized surgical treatment can significantly improve prognosis and increase curative rate and long-term survival rate of locally advanced nonsmall cell lung cancer based on personalized molecular staging.