Locally advanced non-small cell lung cancer: strategies and advances in “individualized surgical treatment
Locally advanced non-small cell lung cancer (LANSCLC) is defined as non-small cell lung cancer with metastasis to mediastinal lymph nodes (N2) and supraclavicular lymph nodes (N3), invasion of the apical lung and important mediastinal structures (T4), and no distant metastasis detected by current screening methods. Invasion of important mediastinal structures is defined as lung cancer that invades the pericardium, heart, great vessels, esophagus and bulge. According to the International Union Against Cancer 2009 International Lung Cancer Staging Criteria, LANSCLC is stage IIIA and stage IIIB lung cancer. According to the literature, LANSCLC accounts for about 60%-70% of NSCLC and about 50% of all lung cancers.
Understanding of LANSCLC classification
There is no unified view on the classification of LANSCLC. According to the author’s own experience and opinion, from the perspective of choosing treatment methods, LANSCLC can be divided into two categories: “resectable” and “unresectable”; from the perspective of treatment results, LANSCLC can be divided into From the perspective of treatment outcome, LANSCLC can be classified into “incidental”, “borderline” and “true”. “Incidental locally advanced non-small cell lung cancer” (incidentallyLANSCLC) refers to cases with preoperative clinical stage I or II, but postoperative pathological examination reveals mediastinal lymph node metastasis. “Marginal locally advanced non-small cell lung cancer” (marginallyLANSCLC) refers to cases with clinically significant lymph node enlargement on imaging, preoperative clinical diagnosis of stage IIIA, and stage IIIB lung cancer in which the tumor has invaded the heart, large blood vessels and augmentation, but complete lung cancer resection can still be achieved in hospitals with Lung cancer. “True locally advanced non-small cell lung cancer” (reallyLANSCLC) refers to lung cancer that has been confirmed to be extensively invading the large blood vessels of the heart and is no longer resectable through dissecting thoracotomy. The concept of “reallyLANSCLC” may not be identical in different hospitals or even in different medical groups in the same hospital. True locally advanced non-small cell lung cancer, which is considered unresectable by thoracotomy in one hospital, can be completely resected by reopening the chest in another hospital, turning it into “borderline locally advanced lung cancer.
The introduction of the new concept of “individualized surgical treatment” and its achievements
Complete resection of lung cancer by surgical techniques was once a milestone in the radical treatment of lung cancer; half a century has passed, but despite the advances in chemotherapy and radiotherapy, and the clinical application of molecularly targeted drugs, complete resection of lung cancer, or supplemented with other treatments, is still considered the most effective treatment option for LANSCLC. The results of recent studies have shown that the prognosis and postoperative survival time of patients vary greatly when the same surgical approach is used to treat the same population in different hospitals and/or the same hospitals. Some stage IIIB LANSCLC invading the cardiac great vessels survive long term without recurrent lung cancer metastasis after complete lung cancer resection, while others with stage IIIA LANSCLC die of distant lung cancer metastasis within a short period of time after complete lung cancer resection. Therefore, how to select patients with LANSCLC who benefit from surgical treatment to receive surgical treatment, how to select patients with LANSCLC who can benefit from preoperative neoadjuvant chemotherapy to administer preoperative neoadjuvant chemotherapy, how to molecularly type LANSCLC for surgical treatment based on molecular markers, and how to guide the treatment based on pharmacogenomic or metabolomic results The “individualized surgical treatment” of lung cancer has been a difficult and cutting-edge topic in the field of lung cancer surgical treatment, such as the selection of adjuvant chemotherapy drugs after surgery for LANSCLC based on molecular markers.
At the end of last century, the author was the first to propose the new “individualized surgical treatment” of lung cancer based on molecular markers at home and abroad, and has made some progress and achievements in more than 10 years of practice. I applied molecular staging of lung cancer, molecular typing of lung cancer, pharmacogenomics, bone marrow and peripheral blood lung cancer micrometastasis for molecular diagnosis, and performed surgical-based multidisciplinary treatment for more than 3,000 cases of LANSCLC invading large blood vessels in the heart.
In the course of surgical treatment of the above-mentioned 3000 LANSCLC patients, the author has innovated more than 30 surgical procedures in the international arena. The main innovative procedures include: pneumonectomy combined with superior vena cava resection and reconstruction for LANSCLC invading the superior vena cava; pneumonectomy combined with left atriotomy for LANSCLC invading the left atrium; bronchopulmonary artery sleeveplasty for LANSCLC invading the pulmonary artery; pneumonectomy combined with thoracic aortic resection and reconstruction for LANSCLC invading the thoracic aorta; tracheal ramus resection and reconstruction, pulmonary artery sleeveplasty, superior vena cava resection and reconstruction for LANSCLC invading tracheal ramus, pulmonary trunk and superior vena cava; tracheal ramus resection + bronchus, pulmonary artery sleeve resection + tracheal ramus reconstruction, pulmonary artery reconstruction + total superior vena cava resection artificial revascularization + partial left atrial resection and reconstruction for LANSCLC invading tracheal ramus, pulmonary trunk, left atrium and superior vena cava LANSCLC; pneumonectomy with partial chest wall resection and reconstruction, superior vena cava resection, right innominate vein, right subclavian vein, right internal static vein and partial right axillary vein resection, right internal jugular vein-right atrium prosthetic revascularization, right axillary vein-right atrium prosthetic revascularization via right jugular incision with median sternotomy approach, treatment of invasion of superior vena cava, right innominate vein, right axillary vein Recurrent central lung cancer in the left upper lobe.
Current consensus on “individualized surgical treatment” for LANSCLC
There is still much controversy regarding the treatment of LANSCLC. However, following the publication of clinical studies of large numbers of cases in recent years, the following consensus has been reached.
1. LANSCLC refers to lung cancer that has been excluded from distant metastasis by existing examination methods, and the tumor invades important mediastinal structures and is accompanied by mediastinal and supraclavicular lymph node metastasis.
2. LANSCLC can be classified into “resectable” and “unresectable” according to the choice of treatment methods, and into “incidental locally advanced non-small cell lung cancer” and “borderline locally advanced non-small cell lung cancer” according to the treatment results. According to the treatment results, LANSCLC can be classified as “incidental locally advanced non-small cell lung cancer”, “borderline locally advanced non-small cell lung cancer” and “true locally advanced non-small cell lung cancer”.
The majority of patients with LANSCLC can receive surgical treatment, and a considerable number of them can achieve long-term survival after surgery; the efficacy of surgical treatment is significantly better than that of medical treatment, therefore, those who are eligible for surgery should strive for surgical treatment.
4. Pre-operative neoadjuvant chemotherapy can indeed reduce the T-stage and N-stage of LANSCLC and improve the resection rate and 5-year survival rate. If the timing of surgery after preoperative neoadjuvant chemotherapy is chosen appropriately, it does not increase the mortality rate of surgery.
5. For LANSCLC invading the heart and large blood vessels, pneumonectomy with expanded heart and large blood vessel resection and reconstruction can be selectively performed. Surgical treatment can significantly improve the 5-year survival rate of patients and improve the prognosis. A significant proportion of these patients do not have the presence of distant metastases in addition to advanced local lesions. Survival of up to 14 years after surgery has been reported in the literature. Preoperative neoadjuvant chemotherapy + surgery should be pursued as a multidisciplinary and comprehensive treatment for these patients. In addition, the choice of this type of surgery should be made carefully, and the principle of choosing surgery should be considered from the conditions of the tumor, the patient, the family, the medical institution and the doctor himself.
”Challenges and suggestions for the future of “individualized surgical treatment
In order to promote the research and clinical treatment level of “individualized surgical treatment” of LANSCLC in China, the author suggests that research and collaboration should be strengthened in the following aspects.
1. Collaboration in multicenter clinical research.
2. Application of pharmacogenomics to guide the selection of beneficiaries of preoperative neoadjuvant chemotherapy for LANSCLC.
3. “Individualized” molecular prediction and molecular diagnosis of LANSCLC micrometastases to select surgical indications and surgical beneficiaries.
4.To carry out “individualized” molecular prediction of LANSCLC prognosis.
5.To carry out “individualized” lung cancer staging based on molecular markers: metastatic and non-metastatic; chemotherapy-sensitive and non-sensitive; surgical benefit and non-benefit.
6.To carry out “molecular pathological staging”, “molecular P-TNM staging”, and “individualized molecular P-TNM” staging of lung cancer.
7.Applying “pharmacogenomics”, “pharmacoproteomics” and “pharmacometabolomics” to predict “individualized surgical treatment of lung cancer “Pre-operative neoadjuvant chemotherapy and post-operative adjuvant chemotherapy drug sensitivity.
8. Application of genomics, proteomics, metabolomics and mRNA to predict the postoperative survival of different LANSCLC individuals.
We believe that with the development and progress of surgical techniques, improvement of medical treatment methods and equipment, development of molecular biology techniques, and the integration of these multidisciplinary theories and techniques, the day when there will be more and more consensus on “individualized surgical treatment” for LANSCLC, less and less controversy, and better and better efficacy will surely come. The day of less controversy and better efficacy will surely come.