Primary lung cancer (lung cancer) is one of the most common malignant tumors in China. According to data released by the National Tumor Registry in 2014, in 2010, there were 605,900 new cases of lung cancer in China (416,300 for men and 189,600 for women), ranking first in malignant tumors (first for men and second for women) and accounting for 19.59% of new cases of malignant tumors (23.03% for men and 14.75% for women). The incidence rate of lung cancer is 35.23/100,000 (49.27/100,000 for men and 21.66/100,000 for women).
During the same period, the number of lung cancer deaths in China was 486,600 (336,800 for men and 166,200 for women), accounting for 24.87% (26.85% for men and 21.32% for women) of the causes of death from malignant tumors. The mortality rate of lung cancer is 27.93/100,000 (39.79/100,000 for men and 16.62/100,000 for women).
In order to further standardize the diagnosis and treatment behavior of lung cancer in China, improve the level of lung cancer diagnosis and treatment in medical institutions, improve the prognosis of lung cancer patients, and ensure medical quality and medical safety, the Medical Administration of the National Health and Family Planning Commission commissioned the Chinese Anti-Cancer Association Tumor Clinical Chemotherapy Professional Committee to update the original Ministry of Health’s Primary Lung Cancer Diagnosis and Treatment Standards (2010 Edition) and develop the Primary Lung Cancer Treatment Specification (2015 Edition)”. In response to the request of the general thoracic surgeons, we will share with you the chapter on lung cancer surgical treatment and related chapters.
1 Treatment of lung cancer
1.1 Treatment principles
The principle of combining multidisciplinary comprehensive treatment and individualized treatment should be adopted, that is, according to the patient’s physical condition, pathological histological type, molecular typing, invasion scope and development trend of the tumor, multidisciplinary comprehensive treatment mode should be adopted, and surgery, chemotherapy, radiotherapy and molecular targeted therapy should be applied in a planned and reasonable manner, so as to maximize the patient’s survival time, improve survival rate, control tumor progression and The aim is to maximize the survival time, improve survival rate, control tumor progression and improve the quality of life.
1.2 Surgical treatment
1.2.1 Principles of surgical treatment Anatomical pneumonectomy is the main treatment for early-stage lung cancer, and is also an important clinical cure for lung cancer at present. Lung cancer surgery is divided into complete resection, incomplete resection and indeterminate resection. In clinical treatment, complete resection should be strived for in order to remove the tumor completely, reduce metastasis and recurrence, and perform accurate pathological TNM staging and strive for molecular pathological staging to guide comprehensive postoperative treatment. The following surgical principles should be observed for surgically resectable lung cancer.
(1) Comprehensive treatment planning and necessary imaging examinations (clinical staging examination, especially accurate N-stage) should both be completed before surgical treatment. Adequate evaluation is needed to decide the possibility of surgical resection and to develop a surgical plan.
(2) Complete resection of the tumor and regional lymph nodes should be achieved as much as possible, while preserving as much functional normal lung tissue as possible.
(3) Television-assisted thoracoscopic surgery (VATS) is a minimally invasive thoracic surgical technique that has matured in recent years, and VATS and other minimally invasive means are recommended for patients without contraindications to surgery.
(4) Anatomical pneumonectomy (lobectomy, bronchial and vascular sleeve lobectomy or total pneumonectomy) is feasible depending on the patient’s physical condition. If the physical condition does not allow, sublobar resection is performed, of which anatomic lung segmental resection is preferred and pulmonary wedge resection is also feasible.
(5) Indications for anatomic segmental lung resection or pulmonary wedge resection are.
① Patients with advanced age or low pulmonary function, or at major risk for lobectomy;
② CT suggests intrapulmonary peripheral type lesion (meaning located in the lateral 1/3 of the lung parenchyma) with a lesion diameter ≤ 2 cm and any of the following characteristics: pathologically confirmed adenocarcinoma; CT follow-up for more than 1 year with high suspicion of cancer; CT suggests solid component ≤ 50% of the ground glass-like shadow;
(iii) Excision of lung tissue with a cut edge ≥ 2 cm from the lesion margin or a cut edge distance ≥ lesion diameter, with a negative cut edge on intraoperative rapid pathological examination;
④Systematic sampling of hilar and mediastinal lymph nodes should be performed before deciding to perform sublobar resection. At present, sublobar resection for early-stage lung cancer is still in the clinical research stage, and participation in clinical research is encouraged, and it cannot be promoted as a standard procedure.
(6) Complete resection (R0 surgery) In addition to complete resection of the primary lesion, systematic resection of each group of hilar and mediastinal lymph nodes (N1 and N2 lymph nodes) should be routinely performed, and the locations should be marked for pathological examination. At least 3 mediastinal drainage areas (N2 stations) should be cleared or sampled for lymph nodes, and whole lymph node resection should be ensured as much as possible. It is recommended that the right thoracic lymph nodes be cleared to 2R, 3a, 3p, 4R, 7-9 groups of lymph nodes and surrounding soft tissues, and the left thoracic lymph nodes be cleared to 4L, 5-9 groups of lymph nodes and surrounding soft tissues.
(7) Usually the pulmonary veins, pulmonary arteries and finally bronchi should be treated sequentially intraoperatively, or the order of treatment should be decided according to the actual intraoperative situation.
(8) Bronchial sleeve lobectomy is the extent of resection performed to preserve as much lung tissue and lung function as possible under the condition of intraoperative rapid pathological examination to ensure negative margins (including bronchial, pulmonary artery or venous dissection), and the postoperative quality of life of patients is better than that of patients undergoing total pneumonectomy.
(9) For patients with recurrence or isolated lung metastases 6 months after complete lung cancer resection, resection of the recurrent lateral residual lung or lung metastases is feasible if extra-pulmonary distant metastases and cardiopulmonary function and other organic conditions allow.
(10) Patients with stage I and II non-small cell lung cancer (NSCLC) who are evaluated to be inoperable in terms of cardiopulmonary function and other organic conditions may choose radical radiation therapy, radiofrequency ablation therapy and drug therapy.
1.2.2 Indications for surgery
①Stage I, II and some stage III A (T1~2N2M0; T3N1~2M0; T4N0~1M0 can be completely resected) NSCLC and stage I small cell lung cancer (SCLC) (T1~2N0M0);
②Some patients with stage IV NSCLC with solitary contralateral lung metastasis, solitary brain or adrenal metastasis;
③ intrapulmonary nodules with high clinical suspicion of lung cancer, which cannot be diagnosed qualitatively by various examinations, may be surgically explored.
1.2.3 Contraindications to surgery
①Patients with poor general condition, and those who cannot tolerate surgery for important organ functions such as heart, lung, liver and kidney;
②Most of the diagnosed stage IV, most of the stage IIIB and some of the stage IIIA NSCLC.
1.3 Staging model of NSCLC
1.3.1 Comprehensive treatment for patients with stage I NSCLC
① Surgical treatment is preferred, including lobectomy plus systemic hilar and mediastinal lymph node dissection, which can be done by VATS or open chest;
②Anatomical lung segmental or wedge resection plus systematic hilar and mediastinal lymph node dissection or sampling can be considered for some stage IA NSCLC patients with advanced age or low lung function;
(iii) Postoperative adjuvant chemotherapy, radiation therapy and targeted drug therapy are not recommended for patients with completely resected stage IA and IB NSCLC, but stage IB patients with high risk factors may be selectively considered for adjuvant chemotherapy;
④For stage I lung cancer with positive margins, reoperation is recommended; for patients who cannot be operated again for any reason, postoperative chemotherapy combined with radiotherapy is recommended;
⑤ Patients with serious medical complications, advanced age and refusal of surgery can be treated with large split radical radiotherapy.
1.3.2 Comprehensive treatment for patients with stage II NSCLC
(i) Preferred surgical treatment is anatomical pneumonectomy plus systematic hilar and mediastinal lymph node removal or sampling;
②Anatomic lung segmental or wedge resection plus systematic hilar and mediastinal lymph node dissection or sampling may be considered in patients with advanced age or low lung function;
③Patients with complete resection of stage II NSCLC are recommended for postoperative adjuvant chemotherapy;
④When the tumor invades the mural pleura or chest wall, the whole chest wall should be resected at least 2 cm from the upper and lower margins of the nearest rib, and the length of the invaded rib should be at least 5 cm from the tumor ;
⑤ Re-operation is recommended for stage II lung cancer with positive cut margins, and postoperative chemotherapy combined with radiotherapy is recommended for patients who cannot be operated again for any reason.
1.3.3 Comprehensive treatment for patients with stage III NSCLC Locally advanced NSCLC is defined as patients with TNM stage III. Multidisciplinary comprehensive treatment is the best choice for stage III NSCLC. Locally advanced NSCLC is divided into two categories: resectable and unresectable.
(1) Resectable patients with locally advanced NSCLC.
(1) Patients with stage T3N1 NSCLC, surgery is preferred, and adjuvant chemotherapy is performed after surgery.
(2) Patients with stage N2 NSCLC with imaging findings of a single group of mediastinal lymph nodes enlarged and <3 cm in diameter or two groups of mediastinal lymph nodes enlarged but not fused and estimated to be completely resectable should receive comprehensive treatment mainly surgical treatment; preoperative mediastinoscopy, ultrasound endoscopy-guided transbronchial needle aspiration biopsy (EBUS-TBNA) or ultrasound endoscopy-guided The preoperative neoadjuvant chemotherapy should be performed after clarifying the N2 stage, and then surgery should be performed.
For patients with fusion and fixation of mediastinal lymph nodes, radiotherapy, chemotherapy or simultaneous radiotherapy should be performed; for those who have reduced N2 stage after treatment, especially to N0, and whose distant metastases are excluded by re-staging assessment, surgery is recommended in combination with the patient’s organism condition.
③ Some patients with NSCLC in T4N0 to 1 stage.
a : Patients with satellite nodules in the same lung lobes: the preferred treatment is surgical resection, with the option of preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy;
b : Patients with other resectable T4N0 to stage 1 NSCLC: neoadjuvant chemotherapy may be preferred as appropriate, and surgical resection may also be chosen. In case of complete resection, postoperative adjuvant chemotherapy is considered. If the cut margin is positive, postoperative radiotherapy and adjuvant chemotherapy are performed.
(4) Treatment of supraglottic sulcus tumor: For some patients who can be operated, it is suggested that preoperative neoadjuvant synchronous radiotherapy and chemotherapy can be considered first.
(2) Patients with unresectable locally advanced NSCLC.
(i) Imaging suggestive of fusion-like enlarged lymph nodes in the mediastinum, and positive NSCLC confirmed by mediastinoscopy, EBUS-TBNA or EUS-FNA;
②Patients with stage T4N2 to 3 NSCLC;
③Patients with metastatic pleural nodes, malignant pleural fluid and malignant pericardial effusion, patients whose new stage has been categorized as M1 and are not suitable for surgical resection, some cases can be treated with thoracoscopic pleural biopsy or pleural fixation;
④ The preferred treatment for patients with unresectable locally advanced NSCLC is simultaneous radiotherapy.
1.4 Treatment of patients with stage IV NSCLC
Before starting treatment, stage IV NSCLC patients should obtain tumor tissues for EGFR and ALK gene testing, and decide the corresponding treatment strategy according to the EGFR and ALK gene status. Systemic therapy is the main tool for stage IV NSCLC, and the treatment aims to improve patients’ quality of life and prolong their survival.
(1) Treatment of stage IV NSCLC patients with isolated brain metastases.
①Patients with NSCLC with isolated brain metastases and resectable lung lesions, the brain lesions can be surgically resected or treated with stereotactic radiation therapy, while the primary lesions in the chest are treated according to the principle of staging;
For patients with isolated adrenal metastases and resectable pulmonary lesions, surgical resection of the adrenal lesions may be considered, while staging of the primary lesions in the thorax should be performed;
(3) Isolated nodules in the contralateral lung or other lobes of the ipsilateral lung can be treated according to the respective staging of the 2 primary tumors, respectively.
(2) Systemic treatment for patients with stage IV NSCLC.
(1) First-line treatment with EGFR-TKI is recommended for patients with stage IV NSCLC with EGFR gene-sensitive mutations, and first-line treatment with crizotinib is recommended for patients with positive ALK fusion genes;
②Patients with stage IV NSCLC with EGFR-sensitive mutation and ALK fusion gene negative or unknown mutation status should start platinum-containing two-drug systemic chemotherapy as early as possible if the ECOG PS score is 0-1; for patients who are not suitable for platinum-based drug therapy, non-platinum-based two-drug combination regimen chemotherapy can be considered;
③Patients with advanced NSCLC with an ECOG PS score of 2 should be given single-agent chemotherapy, but cytotoxic drug chemotherapy is not recommended for patients with an ECOG PS score >2;
④Current evidence does not support the use of age factors as a basis for selecting chemotherapy regimens;
⑤The options for second-line therapy include doxorubicin, pemetrexed, and EGFR-TKI. patients with EGFR-sensitive mutations, if EGFR-TKI is not applied at first-line and maintenance therapy, EGFR-TKI should be given priority at second-line therapy; for patients with negative EGFR-sensitive mutations, chemotherapy should be given priority;
(6) Patients with stage IV NSCLC with ECOG PS score >2 generally do not benefit from chemotherapy, and best supportive care is recommended. Based on systemic treatment, appropriate local treatments can be selected for specific local conditions in order to improve symptoms and enhance patients’ quality of life.
1.5 SCLC staged treatment model
(1) Stage I SCLC patients: surgery + adjuvant chemotherapy (EP regimen or EC regimen, 4-6 cycles). Postoperative prophylactic brain irradiation (PCI) is recommended.
(2) Patients with stage II-III SCLC: combination of chemotherapy and radiotherapy.
①Sequential or simultaneous chemoradiotherapy can be chosen;
②Synchronous chemoradiotherapy after 2 cycles of induction chemotherapy is recommended for sequential treatment;
(3) For those who achieve disease control, PCI is recommended.
(3) Stage IV SCLC patients: chemotherapy-based combination therapy. First-line recommended EP regimen or EC regimen, IP regimen, IC regimen. 3 months for patients with relapsed disease progression recommended to enter clinical trials. 3-6 months for relapsed patients recommended topotecan, irinotecan, gemcitabine or paclitaxel for disease progression after 6 months of treatment can choose initial treatment regimen. PCI is recommended for patients with effective chemotherapy.
2.Treatment process and follow up
2.1 General process of lung cancer diagnosis and treatment.
2.2 Follow-up
For new lung cancer cases, a complete case file and related information should be established, and regular follow-up and corresponding examination should be conducted after diagnosis and treatment. Specific examination methods include medical history, physical examination, blood biochemical and blood tumor marker examination, imaging examination and endoscopy, etc., aiming at monitoring disease recurrence or treatment-related adverse reactions and assessing quality of life. The frequency of follow-up for postoperative patients is once every 3-6 months within 2 years after treatment, once every 6 months within 2-5 years, and once a year after 5 years.
The formulation of the “Code of Practice for the Treatment of Primary Lung Cancer (2015 Edition)” has referred to the international authoritative guidelines for the treatment of lung cancer and other tumors, while taking into account the actual situation in China. Some of the new drugs listed abroad are not included because they have not been approved for clinical application in China. Since there are large individual differences in the specific conditions of patients in clinical practice, this specification is for reference only.